Asli fine foods - distributor of premium quality ethnic brands in usa, vitobel

Welcome to Asli Fine Foods

Established in 1998, we are one of the leading food and oil distributors holding a range of more than 20,000 premium quality products both in local and International brands. Offering a huge range of gourmet ingredients we cater to the Indian, Pakistani, Bengali, Hispanic, Asian, African communities as well as mainstream markets. All our products are 100% vegetarian, which are also a delicious base to your meat dishes or curries. More >>

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Asli Ginger Garlic Pastes

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Word translation in tooltip with English?Croatian dictionary already incorporated.

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Select a text and instantly get information about it in inline window or translate it via google translate ---------------------------------------------------- Bu da ne ki dediginiz an size ne oldu.

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CantoFish

CantoFish is a popup Cantonese-English dictionary for Firefox. It contains over 200,000 entries and works with both traditional and simplified Chinese characters. The Yale and Jyutping romanization.

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An add-on to convert your text to speech

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Popup chinese dictionary for English-speakers learning Mandarin.

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S3.Google Translator adds the power of Google Translate’s automatic translations to your browser! It supports translation of selected text, entered phrase or whole webpage between any of 80+ langua.

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Japanese to English/German/French/Russian dictionary. Just hover the mouse on top of a word, and a popup appears. Automatically de-inflects verbs and adjectives. Detailed kanji view.

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Allows entry of accented characters using natural shortcuts.

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"Kuai-Translator"-instant translation extended (A simple translator add-on), is a convenient extended to support translation of multiple languages, translation of words can also be a WIKI query.

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Binnen-I be gone

This add-on likely is only useful for users who speak German or visit German language websites - it will remove so called "Binnen-Is" on webpages.

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Ћирилично/латинично пресловљавање, виртуална ћирилична тастатура - Serbian Cyrillic/Latin transliteration and Virtual Cyrillic keyboard

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Georgian-English and English-Georgian online dictionary.

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Google Transliteration (Formerly Google Indic Transliteration)

Allows user to type in Indian Languages. Currently supports Tamil, Hindi, Kannada, Telugu, Malayalam, Arabic, Marathi, Bengali, Nepali, Gujarati, Punjabi, Urdu & Persian(New) on any textarea and in.

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This Add-on is designed exclusively for TnSat Forums and it's built to provide some extra options and enhancements while surfing the various sections

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Input Language Assistant

Automatically switches input language to English when you type in address bar.

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Search term highlighter

Highlights your search terms in Web pages.

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Magicword by Vajehyab. com

Magicword is an anywhere access Persian dictionary provided by vajehyab. com. Just double click on any word anywhere in the browser and you will get its definition in seconds. It supports both Engli.

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Turkish Deasciifier

Turkish deasciifier: converts a Turkish text without Turkish letters into a text with proper Turkish letters. Simply right click in a text box or a text area and choose "Convert to Turkish".

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LookupVijadic

A dictionary tool to lookup Vijadic - Japanese Vietnamese multi dictionary which is very useful to learn and study Japanese.

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Bangladeshi girls treated like cattle - the daily beast, oradexon

Bangladeshi Girls Treated Like Cattle

Tucked away between the mazes of overflowing sewers and tea stalls in Tangail, just a few kilometers outside of Bangladesh’s crowded capital, Dhaka, are rows of brothels with sex workers addicted to a steroid intended for cows.

Bangladesh is one of the few majority-Muslim countries in which prostitution is legal, and the minimum age of the workers is 18. But that law is meaningless in a country so poor that parents are forced to sell their daughters for as little as $200, from as young as nine years of age.

That’s where Oradexon, a steroid meant for cattle, comes into the equation. This medicine meant to fatten cows has become the preferred drug among the madams of Bangladesh. They are using the pills to mask the real age of the underage girls working for sex in their brothels by making them appear older and at the same time making the more ‘seasoned’ sex-worker look plum and voluptuous.

The use of this cow steroid amongst prostitutes in Bangladesh is so widespread that the British charity, ActionAid, which has done some of the most extensive research in the field, reports 90% of commercial sex workers are addicted to the drug. Many of them were turned into addicts by their madams.

Legally available only by prescription, Oradexon is in fact readily available in the teashops that populate Bangladeshi cities. At less than a dollar for a sheet of 100 pills, it is often even cheaper than a cup of tea.

This is a story of a continuous cycle of exploitation: The girls are considered “owned” by their madams, and if they want to get out of the commercial sex business, the girls have to repay their “purchase cost.” The “larger” they get, the more clients they get, inching them closer to freedom. At least that is what they hope, and that’s why many of the sex workers readily take Oradexon. They earn less than 60 cents per client.

Despite the popularity of Oradexon, the majority of the country's estimated 200,000 sex workers remain unaware of the dangerous side effects of the drug, which include heart disease, kidney infections, osteoporosis and heart failure. Oradexon is also highly addictive and has intense withdrawal symptoms, such as skin rashes and chronic migraines.

“It is a basic violation of human's rights to force malnourished, poor underage girls into consuming Oradexon on a daily basis to enhance unnatural physical growth and energy,” Bangladeshi advocate Naila Hussain Chowdhury, founder of Women4Empowerment. says. “The sex trade is using steroids to make young girls physically develop faster and unnaturally. This is a frightening development. The perpetrators operate in an environment of impunity, paying no heed to the health risk, jeopardizing lives of many young girls and women. These are human beings we are talking about, who are illiterate and ignorant to the actual side effects of this medicine.” NGOs working in the field have a responsibility to raise awareness among the women and girls about the dangers of consuming cattle steroids, Chowdhury adds.

“It is the basic right of every citizen to have minimum access to all information related to drugs being sold in open market,” she points out. “Responsible NGOs in this field must be more assertive, to ensure information regarding this particular medicine be accessible to all girls consuming this drug. This is a basic human right.”

Tasmima Hossain, former member of Parliament in Bangladesh and longtime feminist, suggests that the core issue is poverty, which informs every aspect of this problem.

“Poverty pushes women to do anything to survive,” Hossain explains to me. “These pills also suppress the appetite, so the sex workers do not feel how hungry they are.” Hossain contends that this issue is also just one aspect of the much larger issue of women and girls’ oppression in Bangladesh.

“Sex workers are called potita in Bengali, which means ‘the fallen group of society,’” Hossain says. “But the men who sleep with these women are referred to as gentlemen, or Babu . a term of respect given to males. Society creates labels for the benefit of men while degrading women.”

The stories of young Bangladeshi women and girls abusing cow steroids makes me think about how these women are trapped in a system that has no regard for their health or rights. On my last trip to Dhaka, I visited a brothel with a relative conducting research for a major international organization. Often the children born to these women and girls live with their mothers in their brothels, and we saw many of those children hiding under the bed while their mothers had sex with their clients.

These women and girls are already ostracized by society and rejected by their families. They pass that stigma onto their children, who often grow up in the brothels and begin working in them as soon as they are mature enough. With open access to Oradexon, they are at the mercy of the madams who can hide the real age of their youngest victims.

In this twisted tale of exploitation and addiction, controlling the flow of the drug is one thing, but ending the business of exploiting women and girls is even more important.

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Alex Padilla (D-Pacoima) authored along to lawmaking, which takes puff Jan. 1, helter-skelter influence to concerns t… Author SF Chron Government Simi Depression, Kaliph. -- It took fewer than 24 hours of chum around with annoy ingredient be advisable for Texas Gov. Wrick Perry prevalent reminder helpless eBay captaincy director Meg Whitman -- a Glove Romney cicerone -- turn this way she superannuated in all directions... Author Capitol Hebdomadal/ LA Present Governmental Gov. Jerry Brownish aforesaid assumed Wednesday he create demo on tap accentuate funerals hateful, but he debauched lawmaking grace elsewhere-of a mind to would alteration illegitimate a difficulty fighting, delivering courts change single-given lose concentration eradicate affect activity is a correction of discharge delivery. Country Subunit. Ted Place (recur-… Author Capitol Hebdomadal/ LA Present Governmental

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Level monitoring - guided wave radar level sensor and transmitter, flexar

Flexar®

GUIDED WAVE RADAR LEVEL SENSOR

Proven Flexar® Technology Installed In Thousands Of Bulk Solids Applications Reliable TDR (a. k.a Reflex Radar) Technology Used For Decades “Smart” Transmitter Output For Use With Industry-Leading SiloTrack™ Inventory Management Software Measuring Range Up To 100ft (30m) In Solids And 200ft (60m) In Liquids Unaffected By Airborne Dust, Bulk Density, Temperature, And Other Properties – Ideal For Powders And Pneumatically Filled Solid Process Temperatures To +300°F (150°C) No Field Calibration Required - Easy To Install And Setup Optional Analog Output For Easy Connection To Existing Control Systems Or Indicating Devices Wireless Sensor Interface Solutions (Click Here) SiloTrack(TM) PC-Based Inventory Management Solutions (Click Here) HMI2 Local Operator Interface Option (Click Here)

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FLEXAR® GUIDED WAVE RADAR Level Sensor

Overview

The Flexar® continuous level measurement system is a smart guided wave radar device used for monitoring the level of powders, granules and other bulk solids as well as many liquids and slurries. It is also suitable for use with a variety of liquids and some slurries. It is used in a wide assortment of vessels and industries for measuring levels up to 200ft (60m) in height. Bringing the Pieces Together: Manufactured at our facility in Elburn, IL, we uniquely combine this proven and strategically acquired technology with almost five decades of expertise and focus in powder and bulk solids applications, and with our SiloTrack™ inventory management software interface. Monitor Technologies uniquely provides the best solutions in level measurement and inventory management of powders and bulk solids. The Flexar guided wave radar level sensor and/or transmitter requires no field calibration or re-calibration and can be setup easily by customer personnel without the use of any special tools or training. Flexar units are suited for almost any application, can operate with process temperatures up to 392° F (200°C), can be provided with a variety of process connections and can work reliably with materials having a wide range of bulk densities and dielectric constants. Flexar is available with a choice of two outputs. The standard output is a “smart” interface for use with SiloTrack™ Version 3.5 PC-based inventory management software. This network-ready software provides a flexible graphical interface for up to 128 “smart” output sensors. In lieu of this “smart” output, an optional analog output is also available.

Principle of Operation

Flexar ® smart guided wave radar level sensors and transmitters operate using TDR (time domain reflectometry) principles that were first developed in the middle part of the 20th century for use in the geological field. Further development of TDR led to its use in the telecommunication industry for detecting breaks in cables. Flexar technology was pioneered in the mid-late 1990’s when TDR was applied to level measuring applications within the process measurement industry.

In the application of TDR for process level measurement micro-pulses are continuously transmitted along a probe or “wave guide” at the speed of light. As soon as the pulses reach the material surface they reflect back to the sensor electronics unit. The time-of-flight of the pulses is calculated and directly related to the distance from the point at which the sensor is mounted on the top of the vessel to the material surface (level). The output from the electronics is continuously updated as the level of the material surface changes.

Flexar smart guided wave radar sensors are equipped with two different measuring modes. In the Direct measuring mode the pulses directly reflect off the material surface back to the electronics unit. This mode is used in applications where the material being measured has a dielectric constant as low as 2.1 for single-cable/rod probes and 1.8 for twin-cable probes.

For materials with dielectric constant below the above mentioned limits, down to as low as 1.4, the second measurement mode is used. This is the TBF (tank bottom following) mode, which is used due to the inability of the pulses to adequately reflect off of the surface of very low dielectric materials. In this measuring mode the Flexar sensor has a “short circuit” at the bottom of the probe at a precisely known distance from the sensor’s mounting point.

In the TBF mode the pulses travel through air at the speed of light and then pass through the material in the vessel at a slower speed, dependent on the specific dielectric constant. The pulses are reflected at the short circuit back up the probe. Flexar sensors in the TBF mode measure the time between the emission and reception of the pulses from the probe short circuit. Because the return time of a pulse when no material is present (through air) is known, we can determine the difference in time between the time-of-flight when empty and the time-of-flight when filled as being directly proportional to the material level in the vessel.

Applications

The Flexar® smart guided wave radar continuous level measuring system can be used in a wide variety of applications, including powders, coarse/fine granular solids, liquids, foodstuffs and even some corrosive substances. Flexar sensor technology is proven in many difficult applications including those where dust levels make it difficult for other technologies to perform reliably, especially at long ranges.

Please consult Monitor's Technical Support Dept. to verify that the Flexar is the best fit for your specific application. Certain conditions (like target material dielectric, silo height, etc.) need to be taken into consideration.

Typical Applications include, but are not limited to:

Feeds

Cement

Bulk Chemicals

Grains

Aggregates

Carbon Black

Coal Dust

Some Liquids

Fly Ash

Silica

Powders

PVC Powder

Flour

Pellets

The maximum range for solids applications is limited to 100ft (30m) due to load limits possible from heavy materials in long ranges. Liquid applications can extend up to 200ft (60m). Any application requiring a continuous level measurement update where the process temperature does not exceed 392° F (200°C) and 580psig (40bar) is possible. The 316 stainless steel probes and threaded or flanged process connections make the Flexar continuous level measuring system ideal for almost any bulk solid and liquid application. To ensure a successful and reliable application, consult with the Monitor Technologies factory-based technical support group to see if Flexar is right for your application.

REMOTE INVENTORY MONITORING If material levels need to be monitored at one or many locations (i. e. your facility, a location down the street, or a plant on the other side of the world) the Flexar® system can provide accurate and reliable measurements. Using SiloTrack™ Version 3.5 software, inventory monitoring from remote locations has never been easier.

WIRELESS SENSOR COMMUNICATION INTERFACE Using the available WirelessEZ interface in your application may help you reduce the installed cost of your SiloTrack™ / Flexar® system even further. The WirelessEZ transceivers use frequency-hopping spread-spectrum wireless technology and operate in the FCC license-free 900MHz band. This provides the longest range and most reliable wireless communications available. Working in conjunction with SiloTrack™ PC-Based inventory management software, the WirelessEZ transceivers provide the most functional and economical inventory management system available today.

Click here for more details on the WirelessEZ and contact our technical support personnel today to see if your application can benefit from a wireless communications solution.

AUXILIARY OUTPUT ENCLOSURES (AOE) A unique feature of the Flexar® Inventory Management System is the ability to incorporate both relay and analog outputs with a standard "smart" output sensor system. These auxiliary relay and/or analog outputs are provided in Auxiliary Output Enclosures (AOE) and are programmed and controlled by either the HMI2 or SiloTrack™ PC-based Inventory Management Software. One analog output and up to four relays (two for HMI2; four for SiloTrack) can be assigned to each of the “smart” output sensors. These can be used to tie the Inventory Management System into remote control systems, sound alarms and for local control functions. Up to 16 analog outputs or 32 relays can be provided within a single enclosure. Up to four AOE’s can be connected on a single network. The AOE can be located close to the point of hardwiring termination minimizing wiring and installation costs.

Features

Solid-State Performance, No Moving Parts. Unlike weight and cable based systems of old, Flexar® guided wave radar level sensors are state-of-the-art and use a time-proven electronic method for continuous measurement of a material level. This non-mechanical means of measurement helps ensure low maintenance.

Measure Materials With Dielectric > 1.4 (TBF Mode). Flexar sensors are capable of sensing and measuring the level of most any material. Materials with dielectric constants below 1.8-2.1 require the use of our TBF (tank bottom following) measuring mode.

Unaffected By Dust And Changes In Material Properties. The technology employed in Flexar units has been proven to be unaffected by airborne dust even during pneumatic filling operations. Unlike through-air technologies such as ultrasonic, through-air radar and laser, Flexar can reliably measure in dusty environments without sacrificing performance or reliability.

Range Of Probes. In order to handle the assortment of applications possible with Flexar . Monitor offers a range of probe styles including single-cable, twin-cable and single-rod. All probes are constructed of 316 stainless steel, have traction load handling capabilities suitable for their respective applications and are easily field replaceable. Consult with Monitor’s factory-based technical support personnel to select the right probe style for your application.

Assortment Of Process Connections. To meet the required bulk solids and liquid applications we have prepared a selection of process connections that will ensure a smooth and simple installation. Flexar sensors can be provided with 1-1/2” NPT, 1-1/2” BSP G, 2” ANSI or DIN DN50PN40 flange connections. Probe type will determine the available process connections.

Dual Compartment Enclosure. The Flexar smart guided wave radar sensor uses an enclosure with two compartments, each with its own access cover. This allows separation of access for wiring and setup/display. The setup/display compartment is provided with a cover window allowing local viewing of the LCD display. In addition, every unit is provided with either two 1/2” NPT conduit entrances (NPT threaded and ANSI flanged process connections) or M20 cable connectors (BSP threaded and DN flanged process connections).

Local LCD Display And Setup. Each sensor includes a built-in user interface consisting of a three-line backlit LCD display, three pushbuttons and three magnetic sensors (used to perform setup and interact with the unit without having to remove the display cover).

Universal Power Supply. Power supply choices include a universal high voltage option 100-240 VAC and a low voltage 24 VAC/VDC option.

Choice of outputs. The standard output for all Flexar guided wave radar units is a “smart” RS-485 communications interface for use with SiloTrack™ Version 3.5 inventory management software. In lieu of this “smart” interface an analog 4-20mA output is available.

R emote electronics available. The standard unit includes the electronics integrally mounted with the sensor. However, remote mounted electronics is optionally available for applications where the electronics are desired to be mounted away from the probe due to extreme vibration, temperature or for convenient access to the local operator interface. The remote electronics version includes a pre-wired 16.4ft (5m) interconnecting cable.

All units include the CE mark and are approved for use in ordinary locations.

Single Cable 0.31” (8mm)

Single Flexible 316 SS cable with large or small counterweight

HMI2 Operator Interface Control Console

The HMI2 operator interface control console provides convenient, local interface for Monitor’s “Smart” RS-485 SiloPatrol® SMU SE cable-based inventory monitoring sensors and/or Flexar® guided wave radar sensors. HMI2 allows for monitoring up to 32 SMU and/or Flexar sensors. The multi-functional HMI2 controls sensor operations, displays measured and calculated data and performs/displays system and sensor diagnostic messages. The HMI2 is easily programmed to display calculated level, volume, weight or percent in addition to the basic distance measurement. Manual readings are taken by depressing the MEAS button, followed by the channel number, followed by ENTER. The HMI2 can also be programmed to operate the SMU “Smart” RS-485 sensors automatically. Menu options allow the user to select days of SMU operation (such as Mon.-Fri.), time window (such as 7 a. m.-3 p. m.) and measurement interval (minimum 30 minutes).

SiloTrack(TM) PC-Based Inventory Management Software SiloTrack™ Version 3.5 Inventory Management Software provides users with an unsurpassed, flexible graphical interface for SiloPatrol® SE “smart” output sensors. Together, SiloTrack Server and Client software can provide inventory monitoring and management to a virtually unlimited number of users, both internal and external to your facility. This allows easy implementation of remote monitoring and vendor managed inventory programs.

SiloTrack capabilities include: - Monitor up to 128 sensors/with up to 5 sensors per vessel - Easy to set up and use - Network capable - Remote monitoring via LAN, Internet/WAN or dial-up - Available in English/Spanish language - Automatic and manual measurement initiation - Curve-fit weight table - Enhanced 3-D type silo graphics - Export silo history and alarm data - Automatic Reports and Scheduling - Set up four alarms per silo - Alarm notification via e-mail, fax, etc.

Specifications

Teflon® is a registered trademark of Dupont Chemical Co. Windows® is a registered trademarks of the Microsoft Corporation RSView® is a registered trademark of Rockwell Automation Wonderware® is a registered trademark of Wonderware Corporation Intellution® is a registered trademark of Intellution, Inc. Cimplicity® is a registered trademark of General Electric Company Bluetooth® is a registered trademark of Bluetooth SIG, Inc. AndroidTM is a trademark of Google Inc. ModbusTM is a trademark of Schneider Electric / Modicon

Warranty

Monitor Technologies LLC warrants each Flexar® guided wave radar continuous level measurement system and HMI2 it manufactures to be free from defects in material and workmanship under normal use and service within two (2) years from the date of purchase. The purchaser must give notice of any defect to Monitor within the warranty period, return the product intact and pre-paid transportation charges. The obligation of Monitor Technologies LLC under warranty is limited to repair or replacement at its factory. This warranty shall not apply to any product which is repaired or altered outside of the Monitor Technologies LLC factory, or which has been subject to misuse, negligence, accident, incorrect wiring by others or improper installation. Monitor Technologies LLC reserves the right to change the design and/or specifications without prior notice.

Part Numbers / Product Configurations

Part # > Product Configuration

16-8111-1111 > FLEXAR,485,S-CBL, O/L, VHI,1-1/2 NPT 16-8111-1131 > FLEXAR,485,S-CBL, O/L, VHI,2"ANSI 16-8111-1141 > FLEXAR,485,S-CBL, O/L, VHI, DN50PN40 16-8111-1211 > FLEXAR,485,S-CBL, O/L, VLO,1-1/2 NPT 16-8111-1231 > FLEXAR,485,S-CBL, O/L, VLO,2"ANSI 16-8111-1241 > FLEXAR,485,S-CBL, O/L, VLO, DN50PN40 16-8111-2111 > FLEXAR,485,S-CBL, H/L, VHI,1-1/2 NPT 16-8111-2131 > FLEXAR,485,S-CBL, H/L, VHI,2"ANSI 16-8111-2211 > FLEXAR,485,S-CBL, H/L, VLO,1-1/2 NPT 16-8111-2231 > FLEXAR,485,S-CBL, H/L, VLO,2"ANSI 16-8112-1112 > FLEXAR,485,LL-CBL, O/L, VHI,1-1/2 NPT 16-8112-1113 > FLEXAR,485,LS-CBL, O/L, VHI,1-1/2 NPT 16-8112-1132 > FLEXAR,485,LL-CBL, O/L, VHI,2"ANSI 16-8112-1133 > FLEXAR,485,LS-CBL, O/L, VHI,2"ANSI 16-8112-1142 > FLEXAR,485,LL-CBL, O/L, VHI, DN50PN40 16-8112-1143 > FLEXAR,485,LS-CBL, O/L, VHI, DN50PN40 16-8112-1212 > FLEXAR,485,LL-CBL, O/L, VLO,1-1/2 NPT 16-8112-1213 > FLEXAR,485,LS-CBL, O/L, VLO,1-1/2 NPT 16-8112-1232 > FLEXAR,485,LL-CBL, O/L, VLO,2"ANSI 16-8112-1233 > FLEXAR,485,LS-CBL, O/L, VLO,2"ANSI 16-8112-1242 > FLEXAR,485,LL-CBL, O/L, VLO, DN50PN40 16-8112-1243 > FLEXAR,485,LS-CBL, O/L, VLO, DN50PN40 16-8112-2112 > FLEXAR,485,LL-CBL, H/L, VHI,1-1/2 NPT 16-8112-2113 > FLEXAR,485,LS-CBL, H/L, VHI,1-1/2 NPT 16-8112-2132 > FLEXAR,485,LL-CBL, H/L, VHI,2"ANSI 16-8112-2133 > FLEXAR,485,LS-CBL, H/L, VHI,2"ANSI 16-8112-2212 > FLEXAR,485,LL-CBL, H/L, VLO,1-1/2 NPT 16-8112-2213 > FLEXAR,485,LS-CBL, H/L, VLO,1-1/2 NPT 16-8112-2232 > FLEXAR,485,LL-CBL, H/L, VLO,2"ANSI 16-8112-2233 > FLEXAR,485,LS-CBL, H/L, VLO,2"ANSI 16-8113-1134 > FLEXAR,485,2-CBL, O/L, VHI,2"ANSI 16-8113-1144 > FLEXAR,485,2-CBL, O/L, VHI, DN50PN40 16-8113-1234 > FLEXAR,485,2-CBL, O/L, VLO,2"ANSI 16-8113-1244 > FLEXAR,485,2-CBL, O/L, VLO, DN50PN40 16-8113-2134 > FLEXAR,485,2-CBL, H/L, VHI,2"ANSI 16-8113-2234 > FLEXAR,485,2-CBL, H/L, VLO,2"ANSI 16-8114-1115 > FLEXAR,485,1-ROD, O/L, VHI,1-1/2 NPT 16-8114-1135 > FLEXAR,485,1-ROD, O/L, VHI,2"ANSI 16-8114-1145 > FLEXAR,485,1-ROD, O/L, VHI, DN50PN40 16-8114-1215 > FLEXAR,485,1-ROD, O/L, VLO,1-1/2 NPT 16-8114-1235 > FLEXAR,485,1-ROD, O/L, VLO,2"ANSI 16-8114-1245 > FLEXAR,485,1-ROD, O/L, VLO, DN50PN40 16-8114-2115 > FLEXAR,485,1-ROD, H/L, VHI,1-1/2 NPT 16-8114-2135 > FLEXAR,485,1-ROD, H/L, VHI,2"ANSI 16-8114-2215 > FLEXAR,485,1-ROD, H/L, VLO,1-1/2 NPT 16-8114-2235 > FLEXAR,485,1-ROD, H/L, VLO,2"ANSI 16-8121-1111 > FLEXAR,4-20,S-CBL, O/L, VHI,1-1/2 NPT 16-8121-1121 > FLEXAR,4-20,S-CBL, O/L, VHI,1-1/2 G 16-8121-1131 > FLEXAR,4-20,S-CBL, O/L, VHI,2"ANSI 16-8121-1141 > FLEXAR,4-20,S-CBL, O/L, VHI, DN50PN40 16-8121-1211 > FLEXAR,4-20,S-CBL, O/L, VLO,1-1/2 NPT 16-8121-1231 > FLEXAR,4-20,S-CBL, O/L, VLO,2"ANSI 16-8121-1241 > FLEXAR,4-20,S-CBL, O/L, VLO, DN50PN40 16-8121-2111 > FLEXAR,4-20,S-CBL, H/L, VHI,1-1/2 NPT 16-8121-2131 > FLEXAR,4-20,S-CBL, H/L, VHI,2"ANSI 16-8121-2211 > FLEXAR,4-20,S-CBL, H/L, VLO,1-1/2 NPT 16-8121-2231 > FLEXAR,4-20,S-CBL, H/L, VLO,2"ANSI 16-8122-1112 > FLEXAR,4-20,LL-CBL, O/L, VHI,1-1/2 NT 16-8122-1113 > FLEXAR,4-20,LS-CBL, O/L, VHI,1-1/2 NT 16-8122-1122 > FLEXAR,4-20,LL-CBL, O/L, VHI,1-1/2 G 16-8122-1123 > FLEXAR,4-20,LS-CBL, O/L, VHI,1-1/2 G 16-8122-1132 > FLEXAR,4-20,LL-CBL, O/L, VHI,2"ANSI 16-8122-1133 > FLEXAR,4-20,LS-CBL, O/L, VHI,2"ANSI 16-8122-1142 > FLEXAR,4-20,LL-CBL, O/L, VHI, DN50PN40 16-8122-1143 > FLEXAR,4-20,LS-CBL, O/L, VHI, DN50PN40 16-8122-1212 > FLEXAR,4-20,LL-CBL, O/L, VLO,1-1/2 NT 16-8122-1213 > FLEXAR,4-20,LS-CBL, O/L, VLO,1-1/2 NT 16-8122-1222 > FLEXAR,4-20,LL-CBL, O/L, VLO,1-1/2 G 16-8122-1232 > FLEXAR,4-20,LL-CBL, O/L, VLO,2"ANSI 16-8122-1233 > FLEXAR,4-20,LS-CBL, O/L, VLO,2"ANSI 16-8122-1242 > FLEXAR,4-20,LL-CBL, O/L, VLO, DN50PN40 16-8122-1243 > FLEXAR,4-20,LS-CBL, O/L, VLO, DN50PN40 16-8122-2112 > FLEXAR,4-20,LL-CBL, H/L, VHI,1-1/2 NT 16-8122-2113 > FLEXAR,4-20,LS-CBL, H/L, VHI,1-1/2 NT 16-8122-2132 > FLEXAR,4-20,LL-CBL, H/L, VHI,2"ANSI 16-8122-2133 > FLEXAR,4-20,LS-CBL, H/L, VHI,2"ANSI 16-8122-2212 > FLEXAR,4-20,LL-CBL, H/L, VLO,1-1/2 NT 16-8122-2213 > FLEXAR,4-20,LS-CBL, H/L, VLO,1-1/2 NT 16-8122-2232 > FLEXAR,4-20,LL-CBL, H/L, VLO,2"ANSI 16-8122-2233 > FLEXAR,4-20,LS-CBL, H/L, VLO,2"ANSI 16-8123-1134 > FLEXAR,4-20,2-CBL, O/L, VHI,2"ANSI 16-8123-1144 > FLEXAR,4-20,2-CBL, O/L, VHI, DN50PN40 16-8123-1234 > FLEXAR,4-20,2-CBL, O/L, VLO,2"ANSI 16-8123-1244 > FLEXAR,4-20,2-CBL, O/L, VLO, DN50PN40 16-8123-2134 > FLEXAR,4-20,2-CBL, H/L, VHI,2"ANSI 16-8123-2234 > FLEXAR,4-20,2-CBL, H/L, VLO,2"ANSI 16-8124-1115 > FLEXAR,4-20,1-ROD, O/L, VHI,1-1/2 NPT 16-8124-1135 > FLEXAR,4-20,1-ROD, O/L, VHI,2"ANSI 16-8124-1145 > FLEXAR,4-20,1-ROD, O/L, VHI, DN50PN40 16-8124-1215 > FLEXAR,4-20,1-ROD, O/L, VLO,1-1/2 NPT 16-8124-1235 > FLEXAR,4-20,1-ROD, O/L, VLO,2"ANSI 16-8124-1245 > FLEXAR,4-20,1-ROD, O/L, VLO, DN50PN40 16-8124-2115 > FLEXAR,4-20,1-ROD, H/L, VHI,1-1/2 NPT 16-8124-2135 > FLEXAR,4-20,1-ROD, H/L, VHI,2"ANSI 16-8124-2215 > FLEXAR,4-20,1-ROD, H/L, VLO,1-1/2 NPT 16-8124-2235 > FLEXAR,4-20,1-ROD, H/L, VLO,2"ANSI 16-8131-1111 > FLEXAR,485/4-20,S-CBL, O/L, VHI,1-1/2 16-8131-2111 > FLEXAR,485/4-20,S-CBL, H/L, VHI, NPT 16-8132-1112 > FLEXAR,485/4-20,LL-CBL, O/L, VHI, NPT 16-8132-1113 > FLEXAR,485/4-20,LS-CBL, O/L, VHI, NPT 16-8132-1132 > FLEXAR,485/4-20,LL-CBL, O/L, VHI,2"AN 16-8132-1212 > FLEXAR,485/4-20,LL-CBL, O/L, VLO, NPT 16-8132-2112 > FLEXAR,485/4-20,LL-CBL, H/L, VHI, NPT 16-8132-2113 > FLEXAR,485/4-20,LS-CBL, H/L, VHI, NPT 16-8132-2132 > FLEXAR,485/4-20,LL-CBL, H/L, VHI,2"AN 16-8221-1111 > FLEXAR, RMT,4-20,S-CBL, O/L, VH1,1-1/2 16-8222-1112 > FLEXAR, RMT,4-20,LL-CBL, O/L,1-1/2 NT 16-8222-1212 > FLEXAR, RMT,4-20,LL-CBL, O/L,1-1/2 NT 16-8231-1211 > FLEXAR, RMT,485/4-20,S-CBL, O/L, VLO,1

Last Rev. February 25, 2016

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Ashwagandha uses, benefits - dosage - herbal database, ashvagandha

Ashwagandha

Scientific Name(s): Withania somnifera (L.) Dunal, (synonym Physalis somnifera L.). Family: Solanaceae (nightshade)

Common Name(s): Withania. aswaganda. winter cherry. Indian ginseng. ajagandha. kanaje Hindi. samm al ferakh. asgand (Hindi), amukkirag (Tamil), amangura (Kannada), asvagandha (Bengali), ashvagandha (Sanskrit), asundha (Gujarati), kuthmithi

Uses

Ashwagandha has been used as an adaptogen, diuretic, and sedative and is available in the United States as a dietary supplement. Trials supporting its clinical use are limited; however, many in vitro and animal experiments suggest effects on the immune and CNS systems, as well as in the pathogenesis of cancer and inflammatory conditions.

Dosing

Dosing information is limited. W. somnifera root powder has generally been used at dosages of 450 mg to 2 g in combination with other preparations.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Abortifacient properties have been reported for ashwagandha. Avoid use.

Interactions

None well documented.

Adverse Reactions

Limited clinical trials are available and case reports are lacking.

Toxicology

Acute toxicity of W. somnifera is modest; at reasonable doses, ashwagandha is nontoxic.

Botany

W. somnifera is an erect, greyish, slightly hairy evergreen shrub that grows to about 1.5 m in height and has fairly long tuberous roots. It is widely cultivated in India and throughout the Middle East and is found in eastern Africa. The small and greenish-yellow flowers can be single or in clusters. The fruit is smooth, round, and fleshy, with many seeds; it is orange-red when ripe and enclosed in a membranous covering. 1

History

The root of W. somnifera is used to make the Ayurvedic tonic ashwagandha. which has been translated to “smells like a horse.” 2 Ashwagandha has been used as an adaptogen, diuretic, and sedative and is available in the United States as a dietary supplement. Other parts of the plant (eg, seeds, leaves) have been used as a pain reliever, to kill lice, and in making soap. The fresh berries have been used as an emetic. 2. 3

Chemistry

The principal bioactive compounds of W. somnifera are withanolides, which are triterpene lactones. More than 40 withanolides and approximately 12 alkaloids and several sitoindosides have been isolated and identified from W. somnifera. The withanolides are structurally related to the ginsenosides of Panax ginseng, hence the common name “Indian ginseng.” 3. 4 Chemical constituents for the roots, fruits, seeds, and stem include withanone; withaferin A; withanolides A, D, an G; and sitoindosides IX, X, VII, and VIII. High performance liquid chromatography techniques to quantify constituents have also been established. 2. 3. 4

Additional compounds, especially withanolides, have been described and evaluated, with variations dependent upon cultivation and varieties. 5. 6. 7 Large amounts of iron are also found in the plant. 4

Uses and Pharmacology

Well-designed clinical studies in which W. somnifera or its extracts are used as a single agent are lacking.

In vitro and animal experiments suggest W. somnifera may possess anti-inflammatory properties. Cultures of cartilage from patients with osteoarthritis and rheumatoid arthritis have been used to demonstrate W. somnifera 's protective effects on chondroplasts. 8. 9. 10. 11 Related effects on cytokines and transcription factors, and suppression of nitric oxide have also been demonstrated. 12 In experiments in rats with induced inflammation, decreased inflammation (paw volume), pain, and disability were noted, as well as an antipyretic effect after administration of W. somnifera root powder. The ulcerogenic effect of W. somnifera was lower than that of indomethacin. 4. 13. 14. 15. 16 A small clinical study evaluating a combination therapy that included ashwagandha demonstrated decreased pain and disability in arthritis, while no changes were observed in the erythrocyte sedimentation rate. 3. 4

Despite more than 30 years of research into a potential role for W. somnifera extracts in the treatment of cancer, clinical trials are lacking. In vitro and animal experiments have been conducted using whole plant extract, ethanol root extracts, aqueous and methanolic leaf extracts, individual withanolides, and withaferin A. Human cancer cell line investigations include HL-60 leukemic and myeloid leukemia cell lines, and bladder, breast, prostate, colon, kidney, gastric, and lung cancer cell lines. Mechanisms of action described include antiproliferative effects, apoptosis, radio-sensitization, mitotic arrest, antiangiogenesis, and enhancement of cell defense mechanisms. 4. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29 Limited studies suggest withanone, withaferin A, and withanolide A have protective effects on glioma cell lines, as well as human fibroblasts, and thereby slow senescence. 30. 31

Experiments in mice have demonstrated decreased lung adenoma tumor incidence with whole plant extract and complete regression of mouse sarcoma tumor with ethanol root extract, as well as radio-sensitizing of carcinomas and increased apoptosis of human breast cancer cells by withaferin A, a steroidal lactone of W. somnifera. 4. 24

Damage to the bladder by cyclophosphamide was ameliorated by W. somnifera extract, 32 as was leukopenia induced by cyclophosphamide. 33

In vitro studies and experiments in animals suggest CNS effects, including modulation of acetylcholinesterase and butyrylcholinesterase activity, inhibition of calcium ion influx, blockade of gamma-aminobutyric acid receptors, modulation of 5-HT 1 and 5-HT 2 receptors, antioxidant activity, and regeneration of neurites, 4. 6. 11 with some researchers suggesting potential applications in Alzheimer and Parkinson diseases. 3. 5. 6

Withania extract protected against pentylenetetrazol-induced seizures in a mouse anticonvulsant model when administered over a 9-week period. 34 The same research group found the extract active in a rat status epilepticus model. 35 A depressant effect on the CNS was indicated by potentiation of pentobarbital effects on the righting reflex in mice, 36 and a mild tranquilizing/relaxant effect in monkeys, cats, dogs, rats, and mice by a total alkaloid extract from the plant roots. 4

A further study of the extract found that it inhibited the development of tolerance to morphine in mice, while suppressing withdrawal symptoms precipitated by naloxone. 37 A withanolide-containing fraction reversed morphine-induced reduction in intestinal motility and confirmed the previous finding of inhibition of development of tolerance to morphine. 38 A role in the management of drug addiction has been suggested. 11

An experiment supported the traditional Ayurvedic medicinal claim that the plant's use could be attributed to effects on learning and memory. Ibotenic acid-induced lesions in intact rat brain that led to cognitive deficit, as measured by performance in a learning task, were reversed by treatment with a withanolide mixture. 39 Limited trials in elderly populations using traditional combination therapies showed mixed results. One study of 2 g of root extract twice daily (in combination) administered over 6 months made no difference in sleep onset times or duration. 40 In another study, increased balance was determined in elderly patients with long-term progressive degenerative ataxia. 41

Immune system effects

Withanolides inhibit murine spleen cell proliferation, 42 and an extract of W. somnifera reversed ochratoxin's suppressive effect on murine macrophage chemotaxis. 43 Withanolide glycosides activated murine macrophages and phagocytosis, and increased lysosomal enzymatic activity secreted by the macrophages, while also displaying antistress activity and positive effects on learning and memory in rats. 44 Alpha-2 macroglobulin synthesis stimulated by inflammation was reduced by W. somnifera extract. 45 Similarly, the extract prevented myelosuppression caused by cyclophosphamide, azathioprine, or prednisolone in mice. 46 In a clinical study, ashwagandha 6 mL root extract administered twice daily for 4 days resulted in increases in CD4 expression, as well as activation of natural killer cells. 47 Additional effects on cytokines and the complement system, lymphocyte proliferation, and humoral and cell-mediated responses have been discussed. 48

Animal experiments have been conducted to describe adaptogenic properties (increased swimming endurance and reduced stress response) of W. somnifera. Clinical trials are lacking. 49. 50. 51. 52. 53. 54. 55. 56. 57

Effects on aging have been promoted, based on claims regarding increased hemoglobin, red blood cell count, hair quality, and melanin levels in a non-peer-reviewed study conducted among healthy men. Serum cholesterol was also reduced and seated-stature improved in this study. 30

Antimicrobial effects 58 and antivenom activity via hyaluronidase inhibition have been described. 59

Dosage

Dosing information is limited.

In a study in which a polyherbal mixture was used for arthritis, W. somnifera 450 mg root powder was administered 4 times per day. 60

In a sleep study with elderly subjects, Withania 2 g root powder was administered with other ingredients twice daily for up to 3 months. 40

In elderly patients with long-term progressive degenerative ataxia, ashwagandha 500 mg tablets were administered 3 times a day for 1 month (in combination). 41

Pregnancy/Lactation

Abortifacient properties have been reported for ashwagandha. Avoid use. 61

In animal experiments, no fetal abnormalities were found in mice fed Withania root extract for 4 weeks. The progeny of experiment animals had a higher birth weight than those of controls. 3 Because of the plant's antiangiogenic and cytotoxic properties, Withania should be avoided during pregnancy.

Interactions

Case reports are lacking. 3 Animal studies report potentiation of phenobarbital-induced sleep, 3 while interactions with some digoxin immunoassays have been demonstrated and are thought to be caused by similarity in chemical structure. 62. 63

Adverse Reactions

Limited clinical trials are available and case reports are lacking.

Toxicology

Acute toxicity of W. somnifera is modest; at reasonable doses ashwagandha is nontoxic. 3. 4

In mice, an oral median lethal dose was determined to be 1,750 mg/kg in 1 study 12 and 1,260 mg/kg by the intraperitoneal route. 64

Subacute intraperitoneal toxicity studies at 100 mg/kg/day for 30 days led to decreased spleen, thymus, and adrenal weights, but no mortality or hematological changes were noted. 64

A longer-term study (180 days) in rats at an oral dose of 100 mg/kg found no lethality, but did discover unfavorable increases in catecholamine content of the heart and decreases in the adrenal glands. 17 At higher dosages (200 mg/kg/day), increases in lung and liver weight were observed. 3. 4

In mice fed the extract of the entire plant as 25% of the total diet, microscopic lesions in the lung and liver were apparent, and vascular and tubular congestion were described. 3

Bibliography

1. Withania somnifera (L.) USDA, NRCS. 2007. The PLANTS Database ( http://plants. usda. gov. 8 April 2010). National Plant Data Center, Baton Rouge, LA 70874-4490 USA. 2. Ganzera M, Choudhary MI, Khan IA. Quantitative HPLC analysis of withanolides in Withania somnifera. Fitoterapia. 2003;74(1-2):68-76. 3. Kulkarni SK, Dhir A. Withania somnifera. an Indian ginseng. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(5):1093-1105. 4. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev. 2000;5(4):334-346. 5. Zhao J, Nakamura N, Hattori M, Kuboyama T, Tohda C, Komatsu K. Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities. Chem Pharm Bull (Tokyo). 2002;50(6):760-765. 6. Choudhary MI, Nawaz SA, ul-Haq Z, et al. Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties. Biochem Biophys Res Commun. 2005;334(1):276-287. 7. Xu YM, Marron MT, Seddon E, et al. 2,3-Dihydrowithaferin A-3beta-O-sulfate, a new potential prodrug of withaferin A from aeroponically grown Withania somnifera. Bioorg Med Chem. 2009;17(6):2210-2214. 8. Sumantran VN, Chandwaskar R, Joshi AK, et al. The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro. Phytother Res. 2008;22(10):1342-1348. 9. Sumantran VN, Kulkarni A, Boddul S, et al. Chondroprotective potential of root extracts of Withania somnifera in osteoarthritis. J Biosci. 2007;32(2):299-307. 10. Singh RH, Narsimhamurthy K, Singh G. Neuronutrient impact of Ayurvedic Rasayana therapy in brain aging. Biogerontology. 2008;9(6):369-374. 11. Lu L, Liu Y, Zhu W, et al. Traditional medicine in the treatment of drug addiction. Am J Drug Alcohol Abuse. 2009;35(1):1-11. 12. Kaileh M, Vanden Berghe W, Heyerick A, et al. Withaferin a strongly elicits IkappaB kinase beta hyperphosphorylation concomitant with potent inhibition of its kinase activity. J Biol Chem. 2007;282(7):4253-4264. 13. Rasool M, Varalakshmi P. Suppressive effect of Withania somnifera root powder on experimental gouty arthritis: An in vivo and in vitro study. Chem Biol Interact. 2006;164(3):174-180. 14. Khanna D, Sethi G, Ahn KS, et al. Natural products as a gold mine for arthritis treatment. Curr Opin Pharmacol. 2007;7(3):344-351. 15. Al-Hindawi MK, Al-Deen IH, Nabi MH, Ismail MA. Anti-inflammatory activity of some Iraqi plants using intact rats. J Ethnopharmacol. 1989;26(2):163-168. 16. Agarwal R, Diwanay S, Patki P, Patwardhan B. Studies on immunomodulatory activity of Withania somnifera (Ashwagandha) extracts in experimental immune inflammation. J Ethnopharmacol. 1999;67(1):27-35. 17. Senthil V, Ramadevi S, Venkatakrishnan V, et al Withanolide induces apoptosis in HL-60 leukemia cells via mitochondria mediated cytochrome c release and caspase activation. Chem Biol Interact. 2007;167(1):19-30. 18. Al-Fatimi M, Friedrich U, Jenett-Siems K. Cytotoxicity of plants used in traditional medicine in Yemen. Fitoterapia. 2005;76(3-4):355-358. 19. Kaur K, Rani G, Widodo N, et al. Evaluation of the anti-proliferative and anti-oxidative activities of leaf extract from in vivo and in vitro raised Ashwagandha. Food Chem Toxicol. 2004;42(12):2015-2020. 20. Niture SK, Rao US, Srivenugopal KS. Chemopreventative strategies targeting the MGMT repair protein: augmented expression in human lymphocytes and tumor cells by ethanolic and aqueous extracts of several Indian medicinal plants. Int J Oncol. 2006;29(5):1269-1278. 21. Mathur R, Gupta SK, Singh N, Mathur S, Kochupillai V, Velpandian T. Evaluation of the effect of Withania somnifera root extracts on cell cycle and angiogenesis. J Ethnopharmacol. 2006;105(3):336-341. 22. Ichikawa H, Takada Y, Shishodia S, Jayaprakasam B, Nair MG, Aggarwal BB. Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB-regulated gene expression. Mol Cancer Ther. 2006;5(6):1434-1445. 23. Stan SD, Hahm ER, Warin R, Singh SV. Withaferin A causes FOXO3a - and Bim-dependent apoptosis and inhibits growth of human breast cancer cells in vivo. Cancer Res. 2008;68(18):7661-7669. 24. Stan SD, Zeng Y, Singh SV. Ayurvedic medicine constituent withaferin a causes G2 and M phase cell cycle arrest in human breast cancer cells. Nutr Cancer. 2008;60(suppl 1):51-60. 25. Mulabagal V, Subbaraju GV, Rao CV, et al. Withanolide sulfoxide from Aswagandha roots inhibits nuclear transcription factor-kappa-B, cyclooxygenase and tumor cell proliferation. Phytother Res. 2009;23(7):987-992. 26. Malik F, Kumar A, Bhushan S, et al. Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL-60 cells by a dietary compound withaferin A with concomitant protection by N-acetyl cysteine. Apoptosis. 2007;12(11):2115-2133. 27. Oh JH, Lee TJ, Kim SH, et al. Induction of apoptosis by withaferin A in human leukemia U937 cells through down-regulation of Akt phosphorylation. Apoptosis. 2008;13(12):1494-1504. 28. Mohan R, Hammers HJ, Bargagna-Mohan P, et al. Withaferin A is a potent inhibitor of angiogenesis. Angiogenesis. 2004;7(2):115-122. 29. Srinivasan S, Ranga RS, Burikhanov R, Han SS, Chendil D. Par-4-dependent apoptosis by the dietary compound withaferin A in prostate cancer cells. Cancer Res. 2007;67(1):246-253. 30. Widodo N, Shah N, Priyandoko D, Ishii T, Kaul SC, Wadhwa R. Deceleration of senescence in normal human fibroblasts by withanone extracted from ashwagandha leaves. J Gerontol A Biol Sci Med Sci. 2009;64(10):1031-1038. 31. Shah N, Kataria H, Kaul SC, et al. Effect of the alcoholic extract of Ashwagandha leaves and its components on proliferation, migration, and differentiation of glioblastoma cells: combinational approach for enhanced differentiation. Cancer Sci. 2009;100(9):1740-1747. 32. Davis L, Kuttan G. Effect of Withania somnifera on cyclophosphamide-induced urotoxicity. Cancer Lett. 2000;148(1):9-17. 33. Davis L, Kuttan G. Suppressive effect of cyclophosphamide-induced toxicity by Withania somnifera extract in mice. J Ethnopharmacol. 1998;62(3):209-214. 34. Kulkarni SK, George B. Anticonvulsant action of Withania somnifera (Ashwaganda) root extract against pentylenetetrazol-induced kindling in mice. Phytother Res. 1996;10(5):447-449. 35. Kulkarni SK, George B, Mathur R. Protective effect of Withania somnifera root extract on electrographic activity in a lithium-pilocarpine model of status epilepticus. Phytother Res. 1998;12(6):451-453. 36. Ahumada F, Trincado MA, Arellano JA, Hancke J, Wikman G. Effect of certain adaptogenic plant extracts on drug-induced narcosis in female and male mice. Phytother Res. 1991;5(1):29-31. 37. Kulkarni S, Ninan I. Inhibition of morphine tolerance and dependence by Withania somnifera in mice. J Ethnopharmacol. 1997;57(3):213-217. 38. Ramarao P, Rao KT, Srivastava RS, Ghosal S. Effects of glycowithanolides from Withania somnifera on morphine-induced inhibition of intestinal motility and tolerance to analgesia in mice. Phytother Res. 1995;9(1):66-68. 39. Bhattacharya SK, Kumar S, Ghosal S. Effects of glycowithanolides from Withania somnifera on an animal model of Alzheimer's disease and perturbed central cholinergic markers of cognition in rats. Phytother Res. 1995;9(2):110-113. 40. Manjunath NK, Telles S. Influence of Yoga and Ayurveda on self-rated sleep in a geriatric population. Indian J Med Res. 2005;121(5):683-690. 41. Sriranjini SJ, Pal PK, Devidas KV, Ganpathy S. Improvement of balance in progressive degenerative cerebellar ataxias after Ayurvedic therapy: a preliminary report. Neurol India. 2009;57(2):166-171. 42. Bähr V, Hänsel R. Immunomodulating properties of 5,20-alpha(R)-dihydroxy-6-alpha-7-alpha-epoxy-1-oxo-(5-alpha)-witha-2,24-dieno lide and solasodine. Planta Med. 1982;44(1):32-33. 43. Dhuley JN. Effect of some Indian herbs on macrophage functions in ochratoxin A treated mice. J Ethnopharmacol. 1997;58(1):15-20. 44. Ghosal S, Lal J, Srivastava R, et al. Immunomodulatory and CNS effects of sitoindosides IX and X, two new glycowithanolides from Withania somnifera. Phytother Res. 1989;3(5):201-206. 45. Anbalagan K, Sadique J. Withania somnifera (Ashwagandha), a rejuvenating herbal drug which controls a-2 macroglobulin synthesis during inflammation. Int J Crude Drug Res. 1985;23(4):177-183. 46. Ziauddin M, Phansalkar N, Patki P, Diwanay S, Patwardhan B. Studies on the immunomodulatory effects of Ashwagandha. J Ethnopharmacol. 1996;50(2):69-76. 47. Mikolai J, Erlandsen A, Murison A, et al. In vivo effects of Ashwagandha ( Withania somnifera ) extract on the activation of lymphocytes. J Altern Complement Med. 2009;15(4):423-430. 48. Rasool M, Varalakshmi P. Immunomodulatory role of Withania somnifera root powder on experimental induced inflammation: An in vivo and in vitro study. Vascul Pharmacol. 2006;44(6):406-410. 49. Singh N, Nath R, Lata A, Singh SP, Kohli RP, Bhargava KP. Withania somnifera (Ashwagandha), a rejuvenating herbal drug which enhances survival during stress (an adaptogen). Int J Crude Drug Res. 1982;20(1):29-35. 50. Bhattacharya SK, Goel RK, Kaur R, Ghosal S. Anti-stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera. Phytother Res. 1987;1(1):32-37. 51. Grandhi A, Mujumdar AM, Patwardhan B. A comparative pharmacological investigation of Ashwagandha and Ginseng. J Ethnopharmacol. 1994;44(3):131-135. 52. Dhuley JN. Effect of ashwagandha on lipid peroxidation in stress-induced animals. J Ethnopharmacol. 1998;60(2):173-178. 53. Archana R, Namasivayam A. Antistressor effect of Withania somnifera. J Ethnopharmacol. 1999;64(1):91-93. 54. Dhuley JN. Adaptogenic and cardioprotective action of ashwagandha in rats and frogs. J Ethnopharmacol. 2000;70(1):57-63. 55. Panda S, Kar A. Withania somnifera and Bauhinia purpurea in the regulation of circulating thyroid hormone concentrations in female mice. J Ethnopharmacol. 1999;67(2):233-239. 56. Singh A, Saxena E, Bhutani KK. Adrenocorticosterone alterations in male, albino mice treated with Trichopus zeylanicus. Withania somnifera. and Panax ginseng preparations. Phytother Res. 2000;14(2):122-125. 57. Bucci LR. Selected herbals and human exercise performance. Am J Clin Nutr. 2000;72(2 suppl):624S-636S. 58. Girish KS, Machiah KD, Ushanandini S, et al. Antimicrobial properties of a non-toxic glycoprotein (WSG) from Withania somnifera (Ashwagandha). J Basic Microbiol. 2006;46(5):365-374. 59. Machiah DK, Girish KS, Gowda TV. A glycoprotein from a folk medicinal plant, Withania somnifera. inhibits hyaluronidase activity of snake venoms. Comp Biochem Physiol C Toxicol Pharmacol. 2006;143(2):158-161. 60. Kulkarni RR, Patki PS, Jog VP, Gandage SC, Patwardhan B. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol. 1991;33(1-2):91-95. 61. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109(3):227-235. 62. Dasgupta A. Herbal supplements and therapeutic drug monitoring: focus on digoxin immunoassays and interactions with St. John's wort. Ther Drug Monit. 2008;30(2):212-217. 63. Dasgupta A, Tso G, Wells A. Effect of Asian ginseng, Siberian ginseng, and Indian ayurvedic medicine Ashwagandha on serum digoxin measurement by Digoxin III, a new digoxin immunoassay. J Clin Lab Anal. 2008;22(4):295-301. 64. Sharada AC, Solmon FE, Devi PU. Toxicity of Withania somnifera root extract in rats and mice. Int J Pharmacognosy. 1993;31(3):205-212.

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More about ashwaganda

Ashwagandha uses, benefits - dosage - herbal database, asgand

Ashwagandha

Scientific Name(s): Withania somnifera (L.) Dunal, (synonym Physalis somnifera L.). Family: Solanaceae (nightshade)

Common Name(s): Withania. aswaganda. winter cherry. Indian ginseng. ajagandha. kanaje Hindi. samm al ferakh. asgand (Hindi), amukkirag (Tamil), amangura (Kannada), asvagandha (Bengali), ashvagandha (Sanskrit), asundha (Gujarati), kuthmithi

Uses

Ashwagandha has been used as an adaptogen, diuretic, and sedative and is available in the United States as a dietary supplement. Trials supporting its clinical use are limited; however, many in vitro and animal experiments suggest effects on the immune and CNS systems, as well as in the pathogenesis of cancer and inflammatory conditions.

Dosing

Dosing information is limited. W. somnifera root powder has generally been used at dosages of 450 mg to 2 g in combination with other preparations.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Abortifacient properties have been reported for ashwagandha. Avoid use.

Interactions

None well documented.

Adverse Reactions

Limited clinical trials are available and case reports are lacking.

Toxicology

Acute toxicity of W. somnifera is modest; at reasonable doses, ashwagandha is nontoxic.

Botany

W. somnifera is an erect, greyish, slightly hairy evergreen shrub that grows to about 1.5 m in height and has fairly long tuberous roots. It is widely cultivated in India and throughout the Middle East and is found in eastern Africa. The small and greenish-yellow flowers can be single or in clusters. The fruit is smooth, round, and fleshy, with many seeds; it is orange-red when ripe and enclosed in a membranous covering. 1

History

The root of W. somnifera is used to make the Ayurvedic tonic ashwagandha. which has been translated to “smells like a horse.” 2 Ashwagandha has been used as an adaptogen, diuretic, and sedative and is available in the United States as a dietary supplement. Other parts of the plant (eg, seeds, leaves) have been used as a pain reliever, to kill lice, and in making soap. The fresh berries have been used as an emetic. 2. 3

Chemistry

The principal bioactive compounds of W. somnifera are withanolides, which are triterpene lactones. More than 40 withanolides and approximately 12 alkaloids and several sitoindosides have been isolated and identified from W. somnifera. The withanolides are structurally related to the ginsenosides of Panax ginseng, hence the common name “Indian ginseng.” 3. 4 Chemical constituents for the roots, fruits, seeds, and stem include withanone; withaferin A; withanolides A, D, an G; and sitoindosides IX, X, VII, and VIII. High performance liquid chromatography techniques to quantify constituents have also been established. 2. 3. 4

Additional compounds, especially withanolides, have been described and evaluated, with variations dependent upon cultivation and varieties. 5. 6. 7 Large amounts of iron are also found in the plant. 4

Uses and Pharmacology

Well-designed clinical studies in which W. somnifera or its extracts are used as a single agent are lacking.

In vitro and animal experiments suggest W. somnifera may possess anti-inflammatory properties. Cultures of cartilage from patients with osteoarthritis and rheumatoid arthritis have been used to demonstrate W. somnifera 's protective effects on chondroplasts. 8. 9. 10. 11 Related effects on cytokines and transcription factors, and suppression of nitric oxide have also been demonstrated. 12 In experiments in rats with induced inflammation, decreased inflammation (paw volume), pain, and disability were noted, as well as an antipyretic effect after administration of W. somnifera root powder. The ulcerogenic effect of W. somnifera was lower than that of indomethacin. 4. 13. 14. 15. 16 A small clinical study evaluating a combination therapy that included ashwagandha demonstrated decreased pain and disability in arthritis, while no changes were observed in the erythrocyte sedimentation rate. 3. 4

Despite more than 30 years of research into a potential role for W. somnifera extracts in the treatment of cancer, clinical trials are lacking. In vitro and animal experiments have been conducted using whole plant extract, ethanol root extracts, aqueous and methanolic leaf extracts, individual withanolides, and withaferin A. Human cancer cell line investigations include HL-60 leukemic and myeloid leukemia cell lines, and bladder, breast, prostate, colon, kidney, gastric, and lung cancer cell lines. Mechanisms of action described include antiproliferative effects, apoptosis, radio-sensitization, mitotic arrest, antiangiogenesis, and enhancement of cell defense mechanisms. 4. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29 Limited studies suggest withanone, withaferin A, and withanolide A have protective effects on glioma cell lines, as well as human fibroblasts, and thereby slow senescence. 30. 31

Experiments in mice have demonstrated decreased lung adenoma tumor incidence with whole plant extract and complete regression of mouse sarcoma tumor with ethanol root extract, as well as radio-sensitizing of carcinomas and increased apoptosis of human breast cancer cells by withaferin A, a steroidal lactone of W. somnifera. 4. 24

Damage to the bladder by cyclophosphamide was ameliorated by W. somnifera extract, 32 as was leukopenia induced by cyclophosphamide. 33

In vitro studies and experiments in animals suggest CNS effects, including modulation of acetylcholinesterase and butyrylcholinesterase activity, inhibition of calcium ion influx, blockade of gamma-aminobutyric acid receptors, modulation of 5-HT 1 and 5-HT 2 receptors, antioxidant activity, and regeneration of neurites, 4. 6. 11 with some researchers suggesting potential applications in Alzheimer and Parkinson diseases. 3. 5. 6

Withania extract protected against pentylenetetrazol-induced seizures in a mouse anticonvulsant model when administered over a 9-week period. 34 The same research group found the extract active in a rat status epilepticus model. 35 A depressant effect on the CNS was indicated by potentiation of pentobarbital effects on the righting reflex in mice, 36 and a mild tranquilizing/relaxant effect in monkeys, cats, dogs, rats, and mice by a total alkaloid extract from the plant roots. 4

A further study of the extract found that it inhibited the development of tolerance to morphine in mice, while suppressing withdrawal symptoms precipitated by naloxone. 37 A withanolide-containing fraction reversed morphine-induced reduction in intestinal motility and confirmed the previous finding of inhibition of development of tolerance to morphine. 38 A role in the management of drug addiction has been suggested. 11

An experiment supported the traditional Ayurvedic medicinal claim that the plant's use could be attributed to effects on learning and memory. Ibotenic acid-induced lesions in intact rat brain that led to cognitive deficit, as measured by performance in a learning task, were reversed by treatment with a withanolide mixture. 39 Limited trials in elderly populations using traditional combination therapies showed mixed results. One study of 2 g of root extract twice daily (in combination) administered over 6 months made no difference in sleep onset times or duration. 40 In another study, increased balance was determined in elderly patients with long-term progressive degenerative ataxia. 41

Immune system effects

Withanolides inhibit murine spleen cell proliferation, 42 and an extract of W. somnifera reversed ochratoxin's suppressive effect on murine macrophage chemotaxis. 43 Withanolide glycosides activated murine macrophages and phagocytosis, and increased lysosomal enzymatic activity secreted by the macrophages, while also displaying antistress activity and positive effects on learning and memory in rats. 44 Alpha-2 macroglobulin synthesis stimulated by inflammation was reduced by W. somnifera extract. 45 Similarly, the extract prevented myelosuppression caused by cyclophosphamide, azathioprine, or prednisolone in mice. 46 In a clinical study, ashwagandha 6 mL root extract administered twice daily for 4 days resulted in increases in CD4 expression, as well as activation of natural killer cells. 47 Additional effects on cytokines and the complement system, lymphocyte proliferation, and humoral and cell-mediated responses have been discussed. 48

Animal experiments have been conducted to describe adaptogenic properties (increased swimming endurance and reduced stress response) of W. somnifera. Clinical trials are lacking. 49. 50. 51. 52. 53. 54. 55. 56. 57

Effects on aging have been promoted, based on claims regarding increased hemoglobin, red blood cell count, hair quality, and melanin levels in a non-peer-reviewed study conducted among healthy men. Serum cholesterol was also reduced and seated-stature improved in this study. 30

Antimicrobial effects 58 and antivenom activity via hyaluronidase inhibition have been described. 59

Dosage

Dosing information is limited.

In a study in which a polyherbal mixture was used for arthritis, W. somnifera 450 mg root powder was administered 4 times per day. 60

In a sleep study with elderly subjects, Withania 2 g root powder was administered with other ingredients twice daily for up to 3 months. 40

In elderly patients with long-term progressive degenerative ataxia, ashwagandha 500 mg tablets were administered 3 times a day for 1 month (in combination). 41

Pregnancy/Lactation

Abortifacient properties have been reported for ashwagandha. Avoid use. 61

In animal experiments, no fetal abnormalities were found in mice fed Withania root extract for 4 weeks. The progeny of experiment animals had a higher birth weight than those of controls. 3 Because of the plant's antiangiogenic and cytotoxic properties, Withania should be avoided during pregnancy.

Interactions

Case reports are lacking. 3 Animal studies report potentiation of phenobarbital-induced sleep, 3 while interactions with some digoxin immunoassays have been demonstrated and are thought to be caused by similarity in chemical structure. 62. 63

Adverse Reactions

Limited clinical trials are available and case reports are lacking.

Toxicology

Acute toxicity of W. somnifera is modest; at reasonable doses ashwagandha is nontoxic. 3. 4

In mice, an oral median lethal dose was determined to be 1,750 mg/kg in 1 study 12 and 1,260 mg/kg by the intraperitoneal route. 64

Subacute intraperitoneal toxicity studies at 100 mg/kg/day for 30 days led to decreased spleen, thymus, and adrenal weights, but no mortality or hematological changes were noted. 64

A longer-term study (180 days) in rats at an oral dose of 100 mg/kg found no lethality, but did discover unfavorable increases in catecholamine content of the heart and decreases in the adrenal glands. 17 At higher dosages (200 mg/kg/day), increases in lung and liver weight were observed. 3. 4

In mice fed the extract of the entire plant as 25% of the total diet, microscopic lesions in the lung and liver were apparent, and vascular and tubular congestion were described. 3

Bibliography

1. Withania somnifera (L.) USDA, NRCS. 2007. The PLANTS Database ( http://plants. usda. gov. 8 April 2010). National Plant Data Center, Baton Rouge, LA 70874-4490 USA. 2. Ganzera M, Choudhary MI, Khan IA. Quantitative HPLC analysis of withanolides in Withania somnifera. Fitoterapia. 2003;74(1-2):68-76. 3. Kulkarni SK, Dhir A. Withania somnifera. an Indian ginseng. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(5):1093-1105. 4. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev. 2000;5(4):334-346. 5. Zhao J, Nakamura N, Hattori M, Kuboyama T, Tohda C, Komatsu K. Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities. Chem Pharm Bull (Tokyo). 2002;50(6):760-765. 6. Choudhary MI, Nawaz SA, ul-Haq Z, et al. Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties. Biochem Biophys Res Commun. 2005;334(1):276-287. 7. Xu YM, Marron MT, Seddon E, et al. 2,3-Dihydrowithaferin A-3beta-O-sulfate, a new potential prodrug of withaferin A from aeroponically grown Withania somnifera. Bioorg Med Chem. 2009;17(6):2210-2214. 8. Sumantran VN, Chandwaskar R, Joshi AK, et al. The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro. Phytother Res. 2008;22(10):1342-1348. 9. Sumantran VN, Kulkarni A, Boddul S, et al. Chondroprotective potential of root extracts of Withania somnifera in osteoarthritis. J Biosci. 2007;32(2):299-307. 10. Singh RH, Narsimhamurthy K, Singh G. Neuronutrient impact of Ayurvedic Rasayana therapy in brain aging. Biogerontology. 2008;9(6):369-374. 11. Lu L, Liu Y, Zhu W, et al. Traditional medicine in the treatment of drug addiction. Am J Drug Alcohol Abuse. 2009;35(1):1-11. 12. Kaileh M, Vanden Berghe W, Heyerick A, et al. Withaferin a strongly elicits IkappaB kinase beta hyperphosphorylation concomitant with potent inhibition of its kinase activity. J Biol Chem. 2007;282(7):4253-4264. 13. Rasool M, Varalakshmi P. Suppressive effect of Withania somnifera root powder on experimental gouty arthritis: An in vivo and in vitro study. Chem Biol Interact. 2006;164(3):174-180. 14. Khanna D, Sethi G, Ahn KS, et al. Natural products as a gold mine for arthritis treatment. Curr Opin Pharmacol. 2007;7(3):344-351. 15. Al-Hindawi MK, Al-Deen IH, Nabi MH, Ismail MA. Anti-inflammatory activity of some Iraqi plants using intact rats. J Ethnopharmacol. 1989;26(2):163-168. 16. Agarwal R, Diwanay S, Patki P, Patwardhan B. Studies on immunomodulatory activity of Withania somnifera (Ashwagandha) extracts in experimental immune inflammation. J Ethnopharmacol. 1999;67(1):27-35. 17. Senthil V, Ramadevi S, Venkatakrishnan V, et al Withanolide induces apoptosis in HL-60 leukemia cells via mitochondria mediated cytochrome c release and caspase activation. Chem Biol Interact. 2007;167(1):19-30. 18. Al-Fatimi M, Friedrich U, Jenett-Siems K. Cytotoxicity of plants used in traditional medicine in Yemen. Fitoterapia. 2005;76(3-4):355-358. 19. Kaur K, Rani G, Widodo N, et al. Evaluation of the anti-proliferative and anti-oxidative activities of leaf extract from in vivo and in vitro raised Ashwagandha. Food Chem Toxicol. 2004;42(12):2015-2020. 20. Niture SK, Rao US, Srivenugopal KS. Chemopreventative strategies targeting the MGMT repair protein: augmented expression in human lymphocytes and tumor cells by ethanolic and aqueous extracts of several Indian medicinal plants. Int J Oncol. 2006;29(5):1269-1278. 21. Mathur R, Gupta SK, Singh N, Mathur S, Kochupillai V, Velpandian T. Evaluation of the effect of Withania somnifera root extracts on cell cycle and angiogenesis. J Ethnopharmacol. 2006;105(3):336-341. 22. Ichikawa H, Takada Y, Shishodia S, Jayaprakasam B, Nair MG, Aggarwal BB. Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB-regulated gene expression. Mol Cancer Ther. 2006;5(6):1434-1445. 23. Stan SD, Hahm ER, Warin R, Singh SV. Withaferin A causes FOXO3a - and Bim-dependent apoptosis and inhibits growth of human breast cancer cells in vivo. Cancer Res. 2008;68(18):7661-7669. 24. Stan SD, Zeng Y, Singh SV. Ayurvedic medicine constituent withaferin a causes G2 and M phase cell cycle arrest in human breast cancer cells. Nutr Cancer. 2008;60(suppl 1):51-60. 25. Mulabagal V, Subbaraju GV, Rao CV, et al. Withanolide sulfoxide from Aswagandha roots inhibits nuclear transcription factor-kappa-B, cyclooxygenase and tumor cell proliferation. Phytother Res. 2009;23(7):987-992. 26. Malik F, Kumar A, Bhushan S, et al. Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL-60 cells by a dietary compound withaferin A with concomitant protection by N-acetyl cysteine. Apoptosis. 2007;12(11):2115-2133. 27. Oh JH, Lee TJ, Kim SH, et al. Induction of apoptosis by withaferin A in human leukemia U937 cells through down-regulation of Akt phosphorylation. Apoptosis. 2008;13(12):1494-1504. 28. Mohan R, Hammers HJ, Bargagna-Mohan P, et al. Withaferin A is a potent inhibitor of angiogenesis. Angiogenesis. 2004;7(2):115-122. 29. Srinivasan S, Ranga RS, Burikhanov R, Han SS, Chendil D. Par-4-dependent apoptosis by the dietary compound withaferin A in prostate cancer cells. Cancer Res. 2007;67(1):246-253. 30. Widodo N, Shah N, Priyandoko D, Ishii T, Kaul SC, Wadhwa R. Deceleration of senescence in normal human fibroblasts by withanone extracted from ashwagandha leaves. J Gerontol A Biol Sci Med Sci. 2009;64(10):1031-1038. 31. Shah N, Kataria H, Kaul SC, et al. Effect of the alcoholic extract of Ashwagandha leaves and its components on proliferation, migration, and differentiation of glioblastoma cells: combinational approach for enhanced differentiation. Cancer Sci. 2009;100(9):1740-1747. 32. Davis L, Kuttan G. Effect of Withania somnifera on cyclophosphamide-induced urotoxicity. Cancer Lett. 2000;148(1):9-17. 33. Davis L, Kuttan G. Suppressive effect of cyclophosphamide-induced toxicity by Withania somnifera extract in mice. J Ethnopharmacol. 1998;62(3):209-214. 34. Kulkarni SK, George B. Anticonvulsant action of Withania somnifera (Ashwaganda) root extract against pentylenetetrazol-induced kindling in mice. Phytother Res. 1996;10(5):447-449. 35. Kulkarni SK, George B, Mathur R. Protective effect of Withania somnifera root extract on electrographic activity in a lithium-pilocarpine model of status epilepticus. Phytother Res. 1998;12(6):451-453. 36. Ahumada F, Trincado MA, Arellano JA, Hancke J, Wikman G. Effect of certain adaptogenic plant extracts on drug-induced narcosis in female and male mice. Phytother Res. 1991;5(1):29-31. 37. Kulkarni S, Ninan I. Inhibition of morphine tolerance and dependence by Withania somnifera in mice. J Ethnopharmacol. 1997;57(3):213-217. 38. Ramarao P, Rao KT, Srivastava RS, Ghosal S. Effects of glycowithanolides from Withania somnifera on morphine-induced inhibition of intestinal motility and tolerance to analgesia in mice. Phytother Res. 1995;9(1):66-68. 39. Bhattacharya SK, Kumar S, Ghosal S. Effects of glycowithanolides from Withania somnifera on an animal model of Alzheimer's disease and perturbed central cholinergic markers of cognition in rats. Phytother Res. 1995;9(2):110-113. 40. Manjunath NK, Telles S. Influence of Yoga and Ayurveda on self-rated sleep in a geriatric population. Indian J Med Res. 2005;121(5):683-690. 41. Sriranjini SJ, Pal PK, Devidas KV, Ganpathy S. Improvement of balance in progressive degenerative cerebellar ataxias after Ayurvedic therapy: a preliminary report. Neurol India. 2009;57(2):166-171. 42. Bähr V, Hänsel R. Immunomodulating properties of 5,20-alpha(R)-dihydroxy-6-alpha-7-alpha-epoxy-1-oxo-(5-alpha)-witha-2,24-dieno lide and solasodine. Planta Med. 1982;44(1):32-33. 43. Dhuley JN. Effect of some Indian herbs on macrophage functions in ochratoxin A treated mice. J Ethnopharmacol. 1997;58(1):15-20. 44. Ghosal S, Lal J, Srivastava R, et al. Immunomodulatory and CNS effects of sitoindosides IX and X, two new glycowithanolides from Withania somnifera. Phytother Res. 1989;3(5):201-206. 45. Anbalagan K, Sadique J. Withania somnifera (Ashwagandha), a rejuvenating herbal drug which controls a-2 macroglobulin synthesis during inflammation. Int J Crude Drug Res. 1985;23(4):177-183. 46. Ziauddin M, Phansalkar N, Patki P, Diwanay S, Patwardhan B. Studies on the immunomodulatory effects of Ashwagandha. J Ethnopharmacol. 1996;50(2):69-76. 47. Mikolai J, Erlandsen A, Murison A, et al. In vivo effects of Ashwagandha ( Withania somnifera ) extract on the activation of lymphocytes. J Altern Complement Med. 2009;15(4):423-430. 48. Rasool M, Varalakshmi P. Immunomodulatory role of Withania somnifera root powder on experimental induced inflammation: An in vivo and in vitro study. Vascul Pharmacol. 2006;44(6):406-410. 49. Singh N, Nath R, Lata A, Singh SP, Kohli RP, Bhargava KP. Withania somnifera (Ashwagandha), a rejuvenating herbal drug which enhances survival during stress (an adaptogen). Int J Crude Drug Res. 1982;20(1):29-35. 50. Bhattacharya SK, Goel RK, Kaur R, Ghosal S. Anti-stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera. Phytother Res. 1987;1(1):32-37. 51. Grandhi A, Mujumdar AM, Patwardhan B. A comparative pharmacological investigation of Ashwagandha and Ginseng. J Ethnopharmacol. 1994;44(3):131-135. 52. Dhuley JN. Effect of ashwagandha on lipid peroxidation in stress-induced animals. J Ethnopharmacol. 1998;60(2):173-178. 53. Archana R, Namasivayam A. Antistressor effect of Withania somnifera. J Ethnopharmacol. 1999;64(1):91-93. 54. Dhuley JN. Adaptogenic and cardioprotective action of ashwagandha in rats and frogs. J Ethnopharmacol. 2000;70(1):57-63. 55. Panda S, Kar A. Withania somnifera and Bauhinia purpurea in the regulation of circulating thyroid hormone concentrations in female mice. J Ethnopharmacol. 1999;67(2):233-239. 56. Singh A, Saxena E, Bhutani KK. Adrenocorticosterone alterations in male, albino mice treated with Trichopus zeylanicus. Withania somnifera. and Panax ginseng preparations. Phytother Res. 2000;14(2):122-125. 57. Bucci LR. Selected herbals and human exercise performance. Am J Clin Nutr. 2000;72(2 suppl):624S-636S. 58. Girish KS, Machiah KD, Ushanandini S, et al. Antimicrobial properties of a non-toxic glycoprotein (WSG) from Withania somnifera (Ashwagandha). J Basic Microbiol. 2006;46(5):365-374. 59. Machiah DK, Girish KS, Gowda TV. A glycoprotein from a folk medicinal plant, Withania somnifera. inhibits hyaluronidase activity of snake venoms. Comp Biochem Physiol C Toxicol Pharmacol. 2006;143(2):158-161. 60. Kulkarni RR, Patki PS, Jog VP, Gandage SC, Patwardhan B. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol. 1991;33(1-2):91-95. 61. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109(3):227-235. 62. Dasgupta A. Herbal supplements and therapeutic drug monitoring: focus on digoxin immunoassays and interactions with St. John's wort. Ther Drug Monit. 2008;30(2):212-217. 63. Dasgupta A, Tso G, Wells A. Effect of Asian ginseng, Siberian ginseng, and Indian ayurvedic medicine Ashwagandha on serum digoxin measurement by Digoxin III, a new digoxin immunoassay. J Clin Lab Anal. 2008;22(4):295-301. 64. Sharada AC, Solmon FE, Devi PU. Toxicity of Withania somnifera root extract in rats and mice. Int J Pharmacognosy. 1993;31(3):205-212.

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Ashwagandha uses, benefits - dosage - herbal database, asvagandha

Ashwagandha

Scientific Name(s): Withania somnifera (L.) Dunal, (synonym Physalis somnifera L.). Family: Solanaceae (nightshade)

Common Name(s): Withania. aswaganda. winter cherry. Indian ginseng. ajagandha. kanaje Hindi. samm al ferakh. asgand (Hindi), amukkirag (Tamil), amangura (Kannada), asvagandha (Bengali), ashvagandha (Sanskrit), asundha (Gujarati), kuthmithi

Uses

Ashwagandha has been used as an adaptogen, diuretic, and sedative and is available in the United States as a dietary supplement. Trials supporting its clinical use are limited; however, many in vitro and animal experiments suggest effects on the immune and CNS systems, as well as in the pathogenesis of cancer and inflammatory conditions.

Dosing

Dosing information is limited. W. somnifera root powder has generally been used at dosages of 450 mg to 2 g in combination with other preparations.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Abortifacient properties have been reported for ashwagandha. Avoid use.

Interactions

None well documented.

Adverse Reactions

Limited clinical trials are available and case reports are lacking.

Toxicology

Acute toxicity of W. somnifera is modest; at reasonable doses, ashwagandha is nontoxic.

Botany

W. somnifera is an erect, greyish, slightly hairy evergreen shrub that grows to about 1.5 m in height and has fairly long tuberous roots. It is widely cultivated in India and throughout the Middle East and is found in eastern Africa. The small and greenish-yellow flowers can be single or in clusters. The fruit is smooth, round, and fleshy, with many seeds; it is orange-red when ripe and enclosed in a membranous covering. 1

History

The root of W. somnifera is used to make the Ayurvedic tonic ashwagandha. which has been translated to “smells like a horse.” 2 Ashwagandha has been used as an adaptogen, diuretic, and sedative and is available in the United States as a dietary supplement. Other parts of the plant (eg, seeds, leaves) have been used as a pain reliever, to kill lice, and in making soap. The fresh berries have been used as an emetic. 2. 3

Chemistry

The principal bioactive compounds of W. somnifera are withanolides, which are triterpene lactones. More than 40 withanolides and approximately 12 alkaloids and several sitoindosides have been isolated and identified from W. somnifera. The withanolides are structurally related to the ginsenosides of Panax ginseng, hence the common name “Indian ginseng.” 3. 4 Chemical constituents for the roots, fruits, seeds, and stem include withanone; withaferin A; withanolides A, D, an G; and sitoindosides IX, X, VII, and VIII. High performance liquid chromatography techniques to quantify constituents have also been established. 2. 3. 4

Additional compounds, especially withanolides, have been described and evaluated, with variations dependent upon cultivation and varieties. 5. 6. 7 Large amounts of iron are also found in the plant. 4

Uses and Pharmacology

Well-designed clinical studies in which W. somnifera or its extracts are used as a single agent are lacking.

In vitro and animal experiments suggest W. somnifera may possess anti-inflammatory properties. Cultures of cartilage from patients with osteoarthritis and rheumatoid arthritis have been used to demonstrate W. somnifera 's protective effects on chondroplasts. 8. 9. 10. 11 Related effects on cytokines and transcription factors, and suppression of nitric oxide have also been demonstrated. 12 In experiments in rats with induced inflammation, decreased inflammation (paw volume), pain, and disability were noted, as well as an antipyretic effect after administration of W. somnifera root powder. The ulcerogenic effect of W. somnifera was lower than that of indomethacin. 4. 13. 14. 15. 16 A small clinical study evaluating a combination therapy that included ashwagandha demonstrated decreased pain and disability in arthritis, while no changes were observed in the erythrocyte sedimentation rate. 3. 4

Despite more than 30 years of research into a potential role for W. somnifera extracts in the treatment of cancer, clinical trials are lacking. In vitro and animal experiments have been conducted using whole plant extract, ethanol root extracts, aqueous and methanolic leaf extracts, individual withanolides, and withaferin A. Human cancer cell line investigations include HL-60 leukemic and myeloid leukemia cell lines, and bladder, breast, prostate, colon, kidney, gastric, and lung cancer cell lines. Mechanisms of action described include antiproliferative effects, apoptosis, radio-sensitization, mitotic arrest, antiangiogenesis, and enhancement of cell defense mechanisms. 4. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29 Limited studies suggest withanone, withaferin A, and withanolide A have protective effects on glioma cell lines, as well as human fibroblasts, and thereby slow senescence. 30. 31

Experiments in mice have demonstrated decreased lung adenoma tumor incidence with whole plant extract and complete regression of mouse sarcoma tumor with ethanol root extract, as well as radio-sensitizing of carcinomas and increased apoptosis of human breast cancer cells by withaferin A, a steroidal lactone of W. somnifera. 4. 24

Damage to the bladder by cyclophosphamide was ameliorated by W. somnifera extract, 32 as was leukopenia induced by cyclophosphamide. 33

In vitro studies and experiments in animals suggest CNS effects, including modulation of acetylcholinesterase and butyrylcholinesterase activity, inhibition of calcium ion influx, blockade of gamma-aminobutyric acid receptors, modulation of 5-HT 1 and 5-HT 2 receptors, antioxidant activity, and regeneration of neurites, 4. 6. 11 with some researchers suggesting potential applications in Alzheimer and Parkinson diseases. 3. 5. 6

Withania extract protected against pentylenetetrazol-induced seizures in a mouse anticonvulsant model when administered over a 9-week period. 34 The same research group found the extract active in a rat status epilepticus model. 35 A depressant effect on the CNS was indicated by potentiation of pentobarbital effects on the righting reflex in mice, 36 and a mild tranquilizing/relaxant effect in monkeys, cats, dogs, rats, and mice by a total alkaloid extract from the plant roots. 4

A further study of the extract found that it inhibited the development of tolerance to morphine in mice, while suppressing withdrawal symptoms precipitated by naloxone. 37 A withanolide-containing fraction reversed morphine-induced reduction in intestinal motility and confirmed the previous finding of inhibition of development of tolerance to morphine. 38 A role in the management of drug addiction has been suggested. 11

An experiment supported the traditional Ayurvedic medicinal claim that the plant's use could be attributed to effects on learning and memory. Ibotenic acid-induced lesions in intact rat brain that led to cognitive deficit, as measured by performance in a learning task, were reversed by treatment with a withanolide mixture. 39 Limited trials in elderly populations using traditional combination therapies showed mixed results. One study of 2 g of root extract twice daily (in combination) administered over 6 months made no difference in sleep onset times or duration. 40 In another study, increased balance was determined in elderly patients with long-term progressive degenerative ataxia. 41

Immune system effects

Withanolides inhibit murine spleen cell proliferation, 42 and an extract of W. somnifera reversed ochratoxin's suppressive effect on murine macrophage chemotaxis. 43 Withanolide glycosides activated murine macrophages and phagocytosis, and increased lysosomal enzymatic activity secreted by the macrophages, while also displaying antistress activity and positive effects on learning and memory in rats. 44 Alpha-2 macroglobulin synthesis stimulated by inflammation was reduced by W. somnifera extract. 45 Similarly, the extract prevented myelosuppression caused by cyclophosphamide, azathioprine, or prednisolone in mice. 46 In a clinical study, ashwagandha 6 mL root extract administered twice daily for 4 days resulted in increases in CD4 expression, as well as activation of natural killer cells. 47 Additional effects on cytokines and the complement system, lymphocyte proliferation, and humoral and cell-mediated responses have been discussed. 48

Animal experiments have been conducted to describe adaptogenic properties (increased swimming endurance and reduced stress response) of W. somnifera. Clinical trials are lacking. 49. 50. 51. 52. 53. 54. 55. 56. 57

Effects on aging have been promoted, based on claims regarding increased hemoglobin, red blood cell count, hair quality, and melanin levels in a non-peer-reviewed study conducted among healthy men. Serum cholesterol was also reduced and seated-stature improved in this study. 30

Antimicrobial effects 58 and antivenom activity via hyaluronidase inhibition have been described. 59

Dosage

Dosing information is limited.

In a study in which a polyherbal mixture was used for arthritis, W. somnifera 450 mg root powder was administered 4 times per day. 60

In a sleep study with elderly subjects, Withania 2 g root powder was administered with other ingredients twice daily for up to 3 months. 40

In elderly patients with long-term progressive degenerative ataxia, ashwagandha 500 mg tablets were administered 3 times a day for 1 month (in combination). 41

Pregnancy/Lactation

Abortifacient properties have been reported for ashwagandha. Avoid use. 61

In animal experiments, no fetal abnormalities were found in mice fed Withania root extract for 4 weeks. The progeny of experiment animals had a higher birth weight than those of controls. 3 Because of the plant's antiangiogenic and cytotoxic properties, Withania should be avoided during pregnancy.

Interactions

Case reports are lacking. 3 Animal studies report potentiation of phenobarbital-induced sleep, 3 while interactions with some digoxin immunoassays have been demonstrated and are thought to be caused by similarity in chemical structure. 62. 63

Adverse Reactions

Limited clinical trials are available and case reports are lacking.

Toxicology

Acute toxicity of W. somnifera is modest; at reasonable doses ashwagandha is nontoxic. 3. 4

In mice, an oral median lethal dose was determined to be 1,750 mg/kg in 1 study 12 and 1,260 mg/kg by the intraperitoneal route. 64

Subacute intraperitoneal toxicity studies at 100 mg/kg/day for 30 days led to decreased spleen, thymus, and adrenal weights, but no mortality or hematological changes were noted. 64

A longer-term study (180 days) in rats at an oral dose of 100 mg/kg found no lethality, but did discover unfavorable increases in catecholamine content of the heart and decreases in the adrenal glands. 17 At higher dosages (200 mg/kg/day), increases in lung and liver weight were observed. 3. 4

In mice fed the extract of the entire plant as 25% of the total diet, microscopic lesions in the lung and liver were apparent, and vascular and tubular congestion were described. 3

Bibliography

1. Withania somnifera (L.) USDA, NRCS. 2007. The PLANTS Database ( http://plants. usda. gov. 8 April 2010). National Plant Data Center, Baton Rouge, LA 70874-4490 USA. 2. Ganzera M, Choudhary MI, Khan IA. Quantitative HPLC analysis of withanolides in Withania somnifera. Fitoterapia. 2003;74(1-2):68-76. 3. Kulkarni SK, Dhir A. Withania somnifera. an Indian ginseng. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(5):1093-1105. 4. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev. 2000;5(4):334-346. 5. Zhao J, Nakamura N, Hattori M, Kuboyama T, Tohda C, Komatsu K. Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities. Chem Pharm Bull (Tokyo). 2002;50(6):760-765. 6. Choudhary MI, Nawaz SA, ul-Haq Z, et al. Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties. Biochem Biophys Res Commun. 2005;334(1):276-287. 7. Xu YM, Marron MT, Seddon E, et al. 2,3-Dihydrowithaferin A-3beta-O-sulfate, a new potential prodrug of withaferin A from aeroponically grown Withania somnifera. Bioorg Med Chem. 2009;17(6):2210-2214. 8. Sumantran VN, Chandwaskar R, Joshi AK, et al. The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro. Phytother Res. 2008;22(10):1342-1348. 9. Sumantran VN, Kulkarni A, Boddul S, et al. Chondroprotective potential of root extracts of Withania somnifera in osteoarthritis. J Biosci. 2007;32(2):299-307. 10. Singh RH, Narsimhamurthy K, Singh G. Neuronutrient impact of Ayurvedic Rasayana therapy in brain aging. Biogerontology. 2008;9(6):369-374. 11. Lu L, Liu Y, Zhu W, et al. Traditional medicine in the treatment of drug addiction. Am J Drug Alcohol Abuse. 2009;35(1):1-11. 12. Kaileh M, Vanden Berghe W, Heyerick A, et al. Withaferin a strongly elicits IkappaB kinase beta hyperphosphorylation concomitant with potent inhibition of its kinase activity. J Biol Chem. 2007;282(7):4253-4264. 13. Rasool M, Varalakshmi P. Suppressive effect of Withania somnifera root powder on experimental gouty arthritis: An in vivo and in vitro study. Chem Biol Interact. 2006;164(3):174-180. 14. Khanna D, Sethi G, Ahn KS, et al. Natural products as a gold mine for arthritis treatment. Curr Opin Pharmacol. 2007;7(3):344-351. 15. Al-Hindawi MK, Al-Deen IH, Nabi MH, Ismail MA. Anti-inflammatory activity of some Iraqi plants using intact rats. J Ethnopharmacol. 1989;26(2):163-168. 16. Agarwal R, Diwanay S, Patki P, Patwardhan B. Studies on immunomodulatory activity of Withania somnifera (Ashwagandha) extracts in experimental immune inflammation. J Ethnopharmacol. 1999;67(1):27-35. 17. Senthil V, Ramadevi S, Venkatakrishnan V, et al Withanolide induces apoptosis in HL-60 leukemia cells via mitochondria mediated cytochrome c release and caspase activation. Chem Biol Interact. 2007;167(1):19-30. 18. Al-Fatimi M, Friedrich U, Jenett-Siems K. Cytotoxicity of plants used in traditional medicine in Yemen. Fitoterapia. 2005;76(3-4):355-358. 19. Kaur K, Rani G, Widodo N, et al. Evaluation of the anti-proliferative and anti-oxidative activities of leaf extract from in vivo and in vitro raised Ashwagandha. Food Chem Toxicol. 2004;42(12):2015-2020. 20. Niture SK, Rao US, Srivenugopal KS. Chemopreventative strategies targeting the MGMT repair protein: augmented expression in human lymphocytes and tumor cells by ethanolic and aqueous extracts of several Indian medicinal plants. Int J Oncol. 2006;29(5):1269-1278. 21. Mathur R, Gupta SK, Singh N, Mathur S, Kochupillai V, Velpandian T. Evaluation of the effect of Withania somnifera root extracts on cell cycle and angiogenesis. J Ethnopharmacol. 2006;105(3):336-341. 22. Ichikawa H, Takada Y, Shishodia S, Jayaprakasam B, Nair MG, Aggarwal BB. Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB-regulated gene expression. Mol Cancer Ther. 2006;5(6):1434-1445. 23. Stan SD, Hahm ER, Warin R, Singh SV. Withaferin A causes FOXO3a - and Bim-dependent apoptosis and inhibits growth of human breast cancer cells in vivo. Cancer Res. 2008;68(18):7661-7669. 24. Stan SD, Zeng Y, Singh SV. Ayurvedic medicine constituent withaferin a causes G2 and M phase cell cycle arrest in human breast cancer cells. Nutr Cancer. 2008;60(suppl 1):51-60. 25. Mulabagal V, Subbaraju GV, Rao CV, et al. Withanolide sulfoxide from Aswagandha roots inhibits nuclear transcription factor-kappa-B, cyclooxygenase and tumor cell proliferation. Phytother Res. 2009;23(7):987-992. 26. Malik F, Kumar A, Bhushan S, et al. Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL-60 cells by a dietary compound withaferin A with concomitant protection by N-acetyl cysteine. Apoptosis. 2007;12(11):2115-2133. 27. Oh JH, Lee TJ, Kim SH, et al. Induction of apoptosis by withaferin A in human leukemia U937 cells through down-regulation of Akt phosphorylation. Apoptosis. 2008;13(12):1494-1504. 28. Mohan R, Hammers HJ, Bargagna-Mohan P, et al. Withaferin A is a potent inhibitor of angiogenesis. Angiogenesis. 2004;7(2):115-122. 29. Srinivasan S, Ranga RS, Burikhanov R, Han SS, Chendil D. Par-4-dependent apoptosis by the dietary compound withaferin A in prostate cancer cells. Cancer Res. 2007;67(1):246-253. 30. Widodo N, Shah N, Priyandoko D, Ishii T, Kaul SC, Wadhwa R. Deceleration of senescence in normal human fibroblasts by withanone extracted from ashwagandha leaves. J Gerontol A Biol Sci Med Sci. 2009;64(10):1031-1038. 31. Shah N, Kataria H, Kaul SC, et al. Effect of the alcoholic extract of Ashwagandha leaves and its components on proliferation, migration, and differentiation of glioblastoma cells: combinational approach for enhanced differentiation. Cancer Sci. 2009;100(9):1740-1747. 32. Davis L, Kuttan G. Effect of Withania somnifera on cyclophosphamide-induced urotoxicity. Cancer Lett. 2000;148(1):9-17. 33. Davis L, Kuttan G. Suppressive effect of cyclophosphamide-induced toxicity by Withania somnifera extract in mice. J Ethnopharmacol. 1998;62(3):209-214. 34. Kulkarni SK, George B. Anticonvulsant action of Withania somnifera (Ashwaganda) root extract against pentylenetetrazol-induced kindling in mice. Phytother Res. 1996;10(5):447-449. 35. Kulkarni SK, George B, Mathur R. Protective effect of Withania somnifera root extract on electrographic activity in a lithium-pilocarpine model of status epilepticus. Phytother Res. 1998;12(6):451-453. 36. Ahumada F, Trincado MA, Arellano JA, Hancke J, Wikman G. Effect of certain adaptogenic plant extracts on drug-induced narcosis in female and male mice. Phytother Res. 1991;5(1):29-31. 37. Kulkarni S, Ninan I. Inhibition of morphine tolerance and dependence by Withania somnifera in mice. J Ethnopharmacol. 1997;57(3):213-217. 38. Ramarao P, Rao KT, Srivastava RS, Ghosal S. Effects of glycowithanolides from Withania somnifera on morphine-induced inhibition of intestinal motility and tolerance to analgesia in mice. Phytother Res. 1995;9(1):66-68. 39. Bhattacharya SK, Kumar S, Ghosal S. Effects of glycowithanolides from Withania somnifera on an animal model of Alzheimer's disease and perturbed central cholinergic markers of cognition in rats. Phytother Res. 1995;9(2):110-113. 40. Manjunath NK, Telles S. Influence of Yoga and Ayurveda on self-rated sleep in a geriatric population. Indian J Med Res. 2005;121(5):683-690. 41. Sriranjini SJ, Pal PK, Devidas KV, Ganpathy S. Improvement of balance in progressive degenerative cerebellar ataxias after Ayurvedic therapy: a preliminary report. Neurol India. 2009;57(2):166-171. 42. Bähr V, Hänsel R. Immunomodulating properties of 5,20-alpha(R)-dihydroxy-6-alpha-7-alpha-epoxy-1-oxo-(5-alpha)-witha-2,24-dieno lide and solasodine. Planta Med. 1982;44(1):32-33. 43. Dhuley JN. Effect of some Indian herbs on macrophage functions in ochratoxin A treated mice. J Ethnopharmacol. 1997;58(1):15-20. 44. Ghosal S, Lal J, Srivastava R, et al. Immunomodulatory and CNS effects of sitoindosides IX and X, two new glycowithanolides from Withania somnifera. Phytother Res. 1989;3(5):201-206. 45. Anbalagan K, Sadique J. Withania somnifera (Ashwagandha), a rejuvenating herbal drug which controls a-2 macroglobulin synthesis during inflammation. Int J Crude Drug Res. 1985;23(4):177-183. 46. Ziauddin M, Phansalkar N, Patki P, Diwanay S, Patwardhan B. Studies on the immunomodulatory effects of Ashwagandha. J Ethnopharmacol. 1996;50(2):69-76. 47. Mikolai J, Erlandsen A, Murison A, et al. In vivo effects of Ashwagandha ( Withania somnifera ) extract on the activation of lymphocytes. J Altern Complement Med. 2009;15(4):423-430. 48. Rasool M, Varalakshmi P. Immunomodulatory role of Withania somnifera root powder on experimental induced inflammation: An in vivo and in vitro study. Vascul Pharmacol. 2006;44(6):406-410. 49. Singh N, Nath R, Lata A, Singh SP, Kohli RP, Bhargava KP. Withania somnifera (Ashwagandha), a rejuvenating herbal drug which enhances survival during stress (an adaptogen). Int J Crude Drug Res. 1982;20(1):29-35. 50. Bhattacharya SK, Goel RK, Kaur R, Ghosal S. Anti-stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera. Phytother Res. 1987;1(1):32-37. 51. Grandhi A, Mujumdar AM, Patwardhan B. A comparative pharmacological investigation of Ashwagandha and Ginseng. J Ethnopharmacol. 1994;44(3):131-135. 52. Dhuley JN. Effect of ashwagandha on lipid peroxidation in stress-induced animals. J Ethnopharmacol. 1998;60(2):173-178. 53. Archana R, Namasivayam A. Antistressor effect of Withania somnifera. J Ethnopharmacol. 1999;64(1):91-93. 54. Dhuley JN. Adaptogenic and cardioprotective action of ashwagandha in rats and frogs. J Ethnopharmacol. 2000;70(1):57-63. 55. Panda S, Kar A. Withania somnifera and Bauhinia purpurea in the regulation of circulating thyroid hormone concentrations in female mice. J Ethnopharmacol. 1999;67(2):233-239. 56. Singh A, Saxena E, Bhutani KK. Adrenocorticosterone alterations in male, albino mice treated with Trichopus zeylanicus. Withania somnifera. and Panax ginseng preparations. Phytother Res. 2000;14(2):122-125. 57. Bucci LR. Selected herbals and human exercise performance. Am J Clin Nutr. 2000;72(2 suppl):624S-636S. 58. Girish KS, Machiah KD, Ushanandini S, et al. Antimicrobial properties of a non-toxic glycoprotein (WSG) from Withania somnifera (Ashwagandha). J Basic Microbiol. 2006;46(5):365-374. 59. Machiah DK, Girish KS, Gowda TV. A glycoprotein from a folk medicinal plant, Withania somnifera. inhibits hyaluronidase activity of snake venoms. Comp Biochem Physiol C Toxicol Pharmacol. 2006;143(2):158-161. 60. Kulkarni RR, Patki PS, Jog VP, Gandage SC, Patwardhan B. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol. 1991;33(1-2):91-95. 61. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109(3):227-235. 62. Dasgupta A. Herbal supplements and therapeutic drug monitoring: focus on digoxin immunoassays and interactions with St. John's wort. Ther Drug Monit. 2008;30(2):212-217. 63. Dasgupta A, Tso G, Wells A. Effect of Asian ginseng, Siberian ginseng, and Indian ayurvedic medicine Ashwagandha on serum digoxin measurement by Digoxin III, a new digoxin immunoassay. J Clin Lab Anal. 2008;22(4):295-301. 64. Sharada AC, Solmon FE, Devi PU. Toxicity of Withania somnifera root extract in rats and mice. Int J Pharmacognosy. 1993;31(3):205-212.

Copyright © 2009 Wolters Kluwer Health

More about ashwaganda

Yosprala Yosprala (aspirin and omeprazole) is a platelet aggregation inhibitor and proton pump inhibitor.

Cuvitru Cuvitru (immune globulin subcutaneous (human)) is indicated as replacement therapy in the treatment.

Erelzi Erelzi (etanercept-szzs) is a tumor necrosis factor (TNF) blocker biosimilar to Enbrel indicated.

Troxyca ER Troxyca ER (oxycodone hydrochloride and naltrexone hydrochloride) is an extended-release.

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Ashwaganda uses, benefits - dosage - herbal database, amukkirag

Ashwagandha

Scientific Name(s): Withania somnifera (L.) Dunal, (synonym Physalis somnifera L.). Family: Solanaceae (nightshade)

Common Name(s): Withania. aswaganda. winter cherry. Indian ginseng. ajagandha. kanaje Hindi. samm al ferakh. asgand (Hindi), amukkirag (Tamil), amangura (Kannada), asvagandha (Bengali), ashvagandha (Sanskrit), asundha (Gujarati), kuthmithi

Uses of Ashwagandha

Ashwagandha has been used as an adaptogen, diuretic, and sedative and is available in the United States as a dietary supplement. Trials supporting its clinical use are limited; however, many in vitro and animal experiments suggest effects on the immune and CNS systems, as well as in the pathogenesis of cancer and inflammatory conditions.

Ashwagandha Dosing

Dosing information is limited. W. somnifera root powder has generally been used at dosages of 450 mg to 2 g in combination with other preparations.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Abortifacient properties have been reported for ashwagandha. Avoid use.

Ashwagandha Interactions

None well documented.

Ashwagandha Adverse Reactions

Limited clinical trials are available and case reports are lacking.

Toxicology

Acute toxicity of W. somnifera is modest; at reasonable doses, ashwagandha is nontoxic.

Botany

W. somnifera is an erect, greyish, slightly hairy evergreen shrub that grows to about 1.5 m in height and has fairly long tuberous roots. It is widely cultivated in India and throughout the Middle East and is found in eastern Africa. The small and greenish-yellow flowers can be single or in clusters. The fruit is smooth, round, and fleshy, with many seeds; it is orange-red when ripe and enclosed in a membranous covering. 1

History

The root of W. somnifera is used to make the Ayurvedic tonic ashwagandha. which has been translated to “smells like a horse.” 2 Ashwagandha has been used as an adaptogen, diuretic, and sedative and is available in the United States as a dietary supplement. Other parts of the plant (eg, seeds, leaves) have been used as a pain reliever, to kill lice, and in making soap. The fresh berries have been used as an emetic. 2. 3

Chemistry

The principal bioactive compounds of W. somnifera are withanolides, which are triterpene lactones. More than 40 withanolides and approximately 12 alkaloids and several sitoindosides have been isolated and identified from W. somnifera. The withanolides are structurally related to the ginsenosides of Panax ginseng, hence the common name “Indian ginseng.” 3. 4 Chemical constituents for the roots, fruits, seeds, and stem include withanone; withaferin A; withanolides A, D, an G; and sitoindosides IX, X, VII, and VIII. High performance liquid chromatography techniques to quantify constituents have also been established. 2. 3. 4

Additional compounds, especially withanolides, have been described and evaluated, with variations dependent upon cultivation and varieties. 5. 6. 7 Large amounts of iron are also found in the plant. 4

Ashwagandha Uses and Pharmacology

Well-designed clinical studies in which W. somnifera or its extracts are used as a single agent are lacking.

In vitro and animal experiments suggest W. somnifera may possess anti-inflammatory properties. Cultures of cartilage from patients with osteoarthritis and rheumatoid arthritis have been used to demonstrate W. somnifera 's protective effects on chondroplasts. 8. 9. 10. 11 Related effects on cytokines and transcription factors, and suppression of nitric oxide have also been demonstrated. 12 In experiments in rats with induced inflammation, decreased inflammation (paw volume), pain, and disability were noted, as well as an antipyretic effect after administration of W. somnifera root powder. The ulcerogenic effect of W. somnifera was lower than that of indomethacin. 4. 13. 14. 15. 16 A small clinical study evaluating a combination therapy that included ashwagandha demonstrated decreased pain and disability in arthritis, while no changes were observed in the erythrocyte sedimentation rate. 3. 4

Despite more than 30 years of research into a potential role for W. somnifera extracts in the treatment of cancer, clinical trials are lacking. In vitro and animal experiments have been conducted using whole plant extract, ethanol root extracts, aqueous and methanolic leaf extracts, individual withanolides, and withaferin A. Human cancer cell line investigations include HL-60 leukemic and myeloid leukemia cell lines, and bladder, breast, prostate, colon, kidney, gastric, and lung cancer cell lines. Mechanisms of action described include antiproliferative effects, apoptosis, radio-sensitization, mitotic arrest, antiangiogenesis, and enhancement of cell defense mechanisms. 4. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29 Limited studies suggest withanone, withaferin A, and withanolide A have protective effects on glioma cell lines, as well as human fibroblasts, and thereby slow senescence. 30. 31

Experiments in mice have demonstrated decreased lung adenoma tumor incidence with whole plant extract and complete regression of mouse sarcoma tumor with ethanol root extract, as well as radio-sensitizing of carcinomas and increased apoptosis of human breast cancer cells by withaferin A, a steroidal lactone of W. somnifera. 4. 24

Damage to the bladder by cyclophosphamide was ameliorated by W. somnifera extract, 32 as was leukopenia induced by cyclophosphamide. 33

In vitro studies and experiments in animals suggest CNS effects, including modulation of acetylcholinesterase and butyrylcholinesterase activity, inhibition of calcium ion influx, blockade of gamma-aminobutyric acid receptors, modulation of 5-HT 1 and 5-HT 2 receptors, antioxidant activity, and regeneration of neurites, 4. 6. 11 with some researchers suggesting potential applications in Alzheimer and Parkinson diseases. 3. 5. 6

Withania extract protected against pentylenetetrazol-induced seizures in a mouse anticonvulsant model when administered over a 9-week period. 34 The same research group found the extract active in a rat status epilepticus model. 35 A depressant effect on the CNS was indicated by potentiation of pentobarbital effects on the righting reflex in mice, 36 and a mild tranquilizing/relaxant effect in monkeys, cats, dogs, rats, and mice by a total alkaloid extract from the plant roots. 4

A further study of the extract found that it inhibited the development of tolerance to morphine in mice, while suppressing withdrawal symptoms precipitated by naloxone. 37 A withanolide-containing fraction reversed morphine-induced reduction in intestinal motility and confirmed the previous finding of inhibition of development of tolerance to morphine. 38 A role in the management of drug addiction has been suggested. 11

An experiment supported the traditional Ayurvedic medicinal claim that the plant's use could be attributed to effects on learning and memory. Ibotenic acid-induced lesions in intact rat brain that led to cognitive deficit, as measured by performance in a learning task, were reversed by treatment with a withanolide mixture. 39 Limited trials in elderly populations using traditional combination therapies showed mixed results. One study of 2 g of root extract twice daily (in combination) administered over 6 months made no difference in sleep onset times or duration. 40 In another study, increased balance was determined in elderly patients with long-term progressive degenerative ataxia. 41

Immune system effects

Withanolides inhibit murine spleen cell proliferation, 42 and an extract of W. somnifera reversed ochratoxin's suppressive effect on murine macrophage chemotaxis. 43 Withanolide glycosides activated murine macrophages and phagocytosis, and increased lysosomal enzymatic activity secreted by the macrophages, while also displaying antistress activity and positive effects on learning and memory in rats. 44 Alpha-2 macroglobulin synthesis stimulated by inflammation was reduced by W. somnifera extract. 45 Similarly, the extract prevented myelosuppression caused by cyclophosphamide, azathioprine, or prednisolone in mice. 46 In a clinical study, ashwagandha 6 mL root extract administered twice daily for 4 days resulted in increases in CD4 expression, as well as activation of natural killer cells. 47 Additional effects on cytokines and the complement system, lymphocyte proliferation, and humoral and cell-mediated responses have been discussed. 48

Animal experiments have been conducted to describe adaptogenic properties (increased swimming endurance and reduced stress response) of W. somnifera. Clinical trials are lacking. 49. 50. 51. 52. 53. 54. 55. 56. 57

Effects on aging have been promoted, based on claims regarding increased hemoglobin, red blood cell count, hair quality, and melanin levels in a non-peer-reviewed study conducted among healthy men. Serum cholesterol was also reduced and seated-stature improved in this study. 30

Antimicrobial effects 58 and antivenom activity via hyaluronidase inhibition have been described. 59

Dosage

Dosing information is limited.

In a study in which a polyherbal mixture was used for arthritis, W. somnifera 450 mg root powder was administered 4 times per day. 60

In a sleep study with elderly subjects, Withania 2 g root powder was administered with other ingredients twice daily for up to 3 months. 40

In elderly patients with long-term progressive degenerative ataxia, ashwagandha 500 mg tablets were administered 3 times a day for 1 month (in combination). 41

Pregnancy/Lactation

Abortifacient properties have been reported for ashwagandha. Avoid use. 61

In animal experiments, no fetal abnormalities were found in mice fed Withania root extract for 4 weeks. The progeny of experiment animals had a higher birth weight than those of controls. 3 Because of the plant's antiangiogenic and cytotoxic properties, Withania should be avoided during pregnancy.

Interactions

Case reports are lacking. 3 Animal studies report potentiation of phenobarbital-induced sleep, 3 while interactions with some digoxin immunoassays have been demonstrated and are thought to be caused by similarity in chemical structure. 62. 63

Adverse Reactions

Limited clinical trials are available and case reports are lacking.

Toxicology

Acute toxicity of W. somnifera is modest; at reasonable doses ashwagandha is nontoxic. 3. 4

In mice, an oral median lethal dose was determined to be 1,750 mg/kg in 1 study 12 and 1,260 mg/kg by the intraperitoneal route. 64

Subacute intraperitoneal toxicity studies at 100 mg/kg/day for 30 days led to decreased spleen, thymus, and adrenal weights, but no mortality or hematological changes were noted. 64

A longer-term study (180 days) in rats at an oral dose of 100 mg/kg found no lethality, but did discover unfavorable increases in catecholamine content of the heart and decreases in the adrenal glands. 17 At higher dosages (200 mg/kg/day), increases in lung and liver weight were observed. 3. 4

In mice fed the extract of the entire plant as 25% of the total diet, microscopic lesions in the lung and liver were apparent, and vascular and tubular congestion were described. 3

Bibliography

1. Withania somnifera (L.) USDA, NRCS. 2007. The PLANTS Database ( http://plants. usda. gov. 8 April 2010). National Plant Data Center, Baton Rouge, LA 70874-4490 USA. 2. Ganzera M, Choudhary MI, Khan IA. Quantitative HPLC analysis of withanolides in Withania somnifera. Fitoterapia. 2003;74(1-2):68-76. 3. Kulkarni SK, Dhir A. Withania somnifera. an Indian ginseng. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(5):1093-1105. 4. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev. 2000;5(4):334-346. 5. Zhao J, Nakamura N, Hattori M, Kuboyama T, Tohda C, Komatsu K. Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities. Chem Pharm Bull (Tokyo). 2002;50(6):760-765. 6. Choudhary MI, Nawaz SA, ul-Haq Z, et al. Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties. Biochem Biophys Res Commun. 2005;334(1):276-287. 7. Xu YM, Marron MT, Seddon E, et al. 2,3-Dihydrowithaferin A-3beta-O-sulfate, a new potential prodrug of withaferin A from aeroponically grown Withania somnifera. Bioorg Med Chem. 2009;17(6):2210-2214. 8. Sumantran VN, Chandwaskar R, Joshi AK, et al. The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro. Phytother Res. 2008;22(10):1342-1348. 9. Sumantran VN, Kulkarni A, Boddul S, et al. Chondroprotective potential of root extracts of Withania somnifera in osteoarthritis. J Biosci. 2007;32(2):299-307. 10. Singh RH, Narsimhamurthy K, Singh G. Neuronutrient impact of Ayurvedic Rasayana therapy in brain aging. Biogerontology. 2008;9(6):369-374. 11. Lu L, Liu Y, Zhu W, et al. Traditional medicine in the treatment of drug addiction. Am J Drug Alcohol Abuse. 2009;35(1):1-11. 12. Kaileh M, Vanden Berghe W, Heyerick A, et al. Withaferin a strongly elicits IkappaB kinase beta hyperphosphorylation concomitant with potent inhibition of its kinase activity. J Biol Chem. 2007;282(7):4253-4264. 13. Rasool M, Varalakshmi P. Suppressive effect of Withania somnifera root powder on experimental gouty arthritis: An in vivo and in vitro study. Chem Biol Interact. 2006;164(3):174-180. 14. Khanna D, Sethi G, Ahn KS, et al. Natural products as a gold mine for arthritis treatment. Curr Opin Pharmacol. 2007;7(3):344-351. 15. Al-Hindawi MK, Al-Deen IH, Nabi MH, Ismail MA. Anti-inflammatory activity of some Iraqi plants using intact rats. J Ethnopharmacol. 1989;26(2):163-168. 16. Agarwal R, Diwanay S, Patki P, Patwardhan B. Studies on immunomodulatory activity of Withania somnifera (Ashwagandha) extracts in experimental immune inflammation. J Ethnopharmacol. 1999;67(1):27-35. 17. Senthil V, Ramadevi S, Venkatakrishnan V, et al Withanolide induces apoptosis in HL-60 leukemia cells via mitochondria mediated cytochrome c release and caspase activation. Chem Biol Interact. 2007;167(1):19-30. 18. Al-Fatimi M, Friedrich U, Jenett-Siems K. Cytotoxicity of plants used in traditional medicine in Yemen. Fitoterapia. 2005;76(3-4):355-358. 19. Kaur K, Rani G, Widodo N, et al. Evaluation of the anti-proliferative and anti-oxidative activities of leaf extract from in vivo and in vitro raised Ashwagandha. Food Chem Toxicol. 2004;42(12):2015-2020. 20. Niture SK, Rao US, Srivenugopal KS. Chemopreventative strategies targeting the MGMT repair protein: augmented expression in human lymphocytes and tumor cells by ethanolic and aqueous extracts of several Indian medicinal plants. Int J Oncol. 2006;29(5):1269-1278. 21. Mathur R, Gupta SK, Singh N, Mathur S, Kochupillai V, Velpandian T. Evaluation of the effect of Withania somnifera root extracts on cell cycle and angiogenesis. J Ethnopharmacol. 2006;105(3):336-341. 22. Ichikawa H, Takada Y, Shishodia S, Jayaprakasam B, Nair MG, Aggarwal BB. Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB-regulated gene expression. Mol Cancer Ther. 2006;5(6):1434-1445. 23. Stan SD, Hahm ER, Warin R, Singh SV. Withaferin A causes FOXO3a - and Bim-dependent apoptosis and inhibits growth of human breast cancer cells in vivo. Cancer Res. 2008;68(18):7661-7669. 24. Stan SD, Zeng Y, Singh SV. Ayurvedic medicine constituent withaferin a causes G2 and M phase cell cycle arrest in human breast cancer cells. Nutr Cancer. 2008;60(suppl 1):51-60. 25. Mulabagal V, Subbaraju GV, Rao CV, et al. Withanolide sulfoxide from Aswagandha roots inhibits nuclear transcription factor-kappa-B, cyclooxygenase and tumor cell proliferation. Phytother Res. 2009;23(7):987-992. 26. Malik F, Kumar A, Bhushan S, et al. Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL-60 cells by a dietary compound withaferin A with concomitant protection by N-acetyl cysteine. Apoptosis. 2007;12(11):2115-2133. 27. Oh JH, Lee TJ, Kim SH, et al. Induction of apoptosis by withaferin A in human leukemia U937 cells through down-regulation of Akt phosphorylation. Apoptosis. 2008;13(12):1494-1504. 28. Mohan R, Hammers HJ, Bargagna-Mohan P, et al. Withaferin A is a potent inhibitor of angiogenesis. Angiogenesis. 2004;7(2):115-122. 29. Srinivasan S, Ranga RS, Burikhanov R, Han SS, Chendil D. Par-4-dependent apoptosis by the dietary compound withaferin A in prostate cancer cells. Cancer Res. 2007;67(1):246-253. 30. Widodo N, Shah N, Priyandoko D, Ishii T, Kaul SC, Wadhwa R. Deceleration of senescence in normal human fibroblasts by withanone extracted from ashwagandha leaves. J Gerontol A Biol Sci Med Sci. 2009;64(10):1031-1038. 31. Shah N, Kataria H, Kaul SC, et al. Effect of the alcoholic extract of Ashwagandha leaves and its components on proliferation, migration, and differentiation of glioblastoma cells: combinational approach for enhanced differentiation. Cancer Sci. 2009;100(9):1740-1747. 32. Davis L, Kuttan G. Effect of Withania somnifera on cyclophosphamide-induced urotoxicity. Cancer Lett. 2000;148(1):9-17. 33. Davis L, Kuttan G. Suppressive effect of cyclophosphamide-induced toxicity by Withania somnifera extract in mice. J Ethnopharmacol. 1998;62(3):209-214. 34. Kulkarni SK, George B. Anticonvulsant action of Withania somnifera (Ashwaganda) root extract against pentylenetetrazol-induced kindling in mice. Phytother Res. 1996;10(5):447-449. 35. Kulkarni SK, George B, Mathur R. Protective effect of Withania somnifera root extract on electrographic activity in a lithium-pilocarpine model of status epilepticus. Phytother Res. 1998;12(6):451-453. 36. Ahumada F, Trincado MA, Arellano JA, Hancke J, Wikman G. Effect of certain adaptogenic plant extracts on drug-induced narcosis in female and male mice. Phytother Res. 1991;5(1):29-31. 37. Kulkarni S, Ninan I. Inhibition of morphine tolerance and dependence by Withania somnifera in mice. J Ethnopharmacol. 1997;57(3):213-217. 38. Ramarao P, Rao KT, Srivastava RS, Ghosal S. Effects of glycowithanolides from Withania somnifera on morphine-induced inhibition of intestinal motility and tolerance to analgesia in mice. Phytother Res. 1995;9(1):66-68. 39. Bhattacharya SK, Kumar S, Ghosal S. Effects of glycowithanolides from Withania somnifera on an animal model of Alzheimer's disease and perturbed central cholinergic markers of cognition in rats. Phytother Res. 1995;9(2):110-113. 40. Manjunath NK, Telles S. Influence of Yoga and Ayurveda on self-rated sleep in a geriatric population. Indian J Med Res. 2005;121(5):683-690. 41. Sriranjini SJ, Pal PK, Devidas KV, Ganpathy S. Improvement of balance in progressive degenerative cerebellar ataxias after Ayurvedic therapy: a preliminary report. Neurol India. 2009;57(2):166-171. 42. Bähr V, Hänsel R. Immunomodulating properties of 5,20-alpha(R)-dihydroxy-6-alpha-7-alpha-epoxy-1-oxo-(5-alpha)-witha-2,24-dieno lide and solasodine. Planta Med. 1982;44(1):32-33. 43. Dhuley JN. Effect of some Indian herbs on macrophage functions in ochratoxin A treated mice. J Ethnopharmacol. 1997;58(1):15-20. 44. Ghosal S, Lal J, Srivastava R, et al. Immunomodulatory and CNS effects of sitoindosides IX and X, two new glycowithanolides from Withania somnifera. Phytother Res. 1989;3(5):201-206. 45. Anbalagan K, Sadique J. Withania somnifera (Ashwagandha), a rejuvenating herbal drug which controls a-2 macroglobulin synthesis during inflammation. Int J Crude Drug Res. 1985;23(4):177-183. 46. Ziauddin M, Phansalkar N, Patki P, Diwanay S, Patwardhan B. Studies on the immunomodulatory effects of Ashwagandha. J Ethnopharmacol. 1996;50(2):69-76. 47. Mikolai J, Erlandsen A, Murison A, et al. In vivo effects of Ashwagandha ( Withania somnifera ) extract on the activation of lymphocytes. J Altern Complement Med. 2009;15(4):423-430. 48. Rasool M, Varalakshmi P. Immunomodulatory role of Withania somnifera root powder on experimental induced inflammation: An in vivo and in vitro study. Vascul Pharmacol. 2006;44(6):406-410. 49. Singh N, Nath R, Lata A, Singh SP, Kohli RP, Bhargava KP. Withania somnifera (Ashwagandha), a rejuvenating herbal drug which enhances survival during stress (an adaptogen). Int J Crude Drug Res. 1982;20(1):29-35. 50. Bhattacharya SK, Goel RK, Kaur R, Ghosal S. Anti-stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera. Phytother Res. 1987;1(1):32-37. 51. Grandhi A, Mujumdar AM, Patwardhan B. A comparative pharmacological investigation of Ashwagandha and Ginseng. J Ethnopharmacol. 1994;44(3):131-135. 52. Dhuley JN. Effect of ashwagandha on lipid peroxidation in stress-induced animals. J Ethnopharmacol. 1998;60(2):173-178. 53. Archana R, Namasivayam A. Antistressor effect of Withania somnifera. J Ethnopharmacol. 1999;64(1):91-93. 54. Dhuley JN. Adaptogenic and cardioprotective action of ashwagandha in rats and frogs. J Ethnopharmacol. 2000;70(1):57-63. 55. Panda S, Kar A. Withania somnifera and Bauhinia purpurea in the regulation of circulating thyroid hormone concentrations in female mice. J Ethnopharmacol. 1999;67(2):233-239. 56. Singh A, Saxena E, Bhutani KK. Adrenocorticosterone alterations in male, albino mice treated with Trichopus zeylanicus. Withania somnifera. and Panax ginseng preparations. Phytother Res. 2000;14(2):122-125. 57. Bucci LR. Selected herbals and human exercise performance. Am J Clin Nutr. 2000;72(2 suppl):624S-636S. 58. Girish KS, Machiah KD, Ushanandini S, et al. Antimicrobial properties of a non-toxic glycoprotein (WSG) from Withania somnifera (Ashwagandha). J Basic Microbiol. 2006;46(5):365-374. 59. Machiah DK, Girish KS, Gowda TV. A glycoprotein from a folk medicinal plant, Withania somnifera. inhibits hyaluronidase activity of snake venoms. Comp Biochem Physiol C Toxicol Pharmacol. 2006;143(2):158-161. 60. Kulkarni RR, Patki PS, Jog VP, Gandage SC, Patwardhan B. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol. 1991;33(1-2):91-95. 61. Ernst E. Herbal medicinal products during pregnancy: are they safe? BJOG. 2002;109(3):227-235. 62. Dasgupta A. Herbal supplements and therapeutic drug monitoring: focus on digoxin immunoassays and interactions with St. John's wort. Ther Drug Monit. 2008;30(2):212-217. 63. Dasgupta A, Tso G, Wells A. Effect of Asian ginseng, Siberian ginseng, and Indian ayurvedic medicine Ashwagandha on serum digoxin measurement by Digoxin III, a new digoxin immunoassay. J Clin Lab Anal. 2008;22(4):295-301. 64. Sharada AC, Solmon FE, Devi PU. Toxicity of Withania somnifera root extract in rats and mice. Int J Pharmacognosy. 1993;31(3):205-212.

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Drugs. com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Data sources include Micromedex® (updated Sep 2nd, 2016), Cerner Multum™ (updated Sep 5th, 2016), Wolters Kluwer™ (updated Aug 8th, 2016) and others. To view content sources and attributions, please refer to our editorial policy .

We comply with the HONcode standard for trustworthy health information - verify here

Copyright © 2000-2016 Drugs. com. All rights reserved.