Pharmacognosy of Ashwagandhaa (Withania somnifera)



Pharmacognosy of Ashwagandhaa (Withania somnifera)
Dr. Hemant Vinze M. S.

Introduction

Ashwagandhaa (Withania somnifera) also known as Indian ginseng, a small tender perennial shrub of the Solanaceae family is found in warm climates. What is ginseng in Chinese medicine, Ashwagandhaa (Withania somnifera) is in Ayurvedic medicine. The odor of the fresh roots of the herb is said to be liken to that of the urine (pee) of horse; hence the epithet Ashwagandhaa (Withania somnifera). 

The Solanaceae is a family of flowering plants, many of which are edible; some are poisonous while some have both edible and toxic parts. Though the name of the family is derived from the Latin Solanum “the nightshade plant”, the further etymology of that word is unclear. It is likely, the name comes from the semblance that some of the flowers bear to the sun and its rays. In fact a species Solanum nigrum is known as the sunberry. Alternatively, it has been suggested the name is derived from the Latin verb solari, meaning “to soothe”. This presumably refers to alleged soothing pharmacological properties of some of the psychoactive species of the family.

According to Anne Van Arsdall, Withania somnifera was called apollinaris and glofwyrt in The Old English Herbarium, and had a legend that Apollo found it first and gave it to the healer Aesculapius.

The author of biography of Alexander the Great, Robin Lane Fox,    claims Withania somnifera has been used in wine in ancient times. [1], [2], [3]

Don’t confuse Ashwagandha (Withania somnifera ) with Physalis alkekengi as both are known as winter cherry. Also Ashwagandha (Withania somnifera) should not be confused with Withania coagulans. It is a different plant. [4], [5]
Other Names

Botanical: Withania somnifera.
Sanskrit: Ashwagandhaa, Waajeekaree, Waraahakarnee, Kaamarupinee, Waajinee, Turagee, Ashwarodhaa, Baladaa,
English: Indian ginseng, Winter cherry, Siberian ginseng, Strykhnos
Arabic: Hajarat el dib
Modern Arabic: Marjan
Bengali: Dhuppa
Gujarati: Asan, Ghodhaakun Ghoda ahan, Asod, Asun,
Hindi:  Ashgandh, Asaganda, Kanaje, Nagori asagandha, Rasbhari
Kannada: Keramaddinagaddi, Kanchuki
Malayalam: Amukkuram Ayamodakam, Trittayu
Marathi: Ashwagandhaa, Askandha, Ghoda, Tilli Dorgunj
Persian:  Meheman
Telugu: Penneru, Waajigandha
Tamil: Amukkara, Amukira, Asuragandi
Urdu: Asgandanagaori
Yemen: Ubad  [6]

Taxonomic  Classification    
    
Kingdom: Plantae
Unranked: Angiosperms
Unranked: Eudicots
Unranked: Asterids
Family: Solanaceae
Division: Magnoliphyta                                
Class: Magnolipsida
Order: Solanales

There are over 20 species of Withania that occur in the dry parts of India, North Africa, Middle East and Mediterranean. These include Withania coagulens and Withania simonii, the roots of which are sometimes used interchangeably with those of Withania somnifera. Of these Withania somnifera has been extensively domesticated from the wild form. [7]

Geographical Distribution

Ashwagandhaa (Withania somnifera) grows prolifically in India, Pakistan, and Sri Lanka. It is commercially cultivated in Madhya Pradesh a state in India. It is also found in Congo, South Africa, Egypt, Morocco, Jordan and Afghanistan. In India, at least five different cultivars have been developed for increased root size and adaptation to different climates.

This tender herb is grown as an annual small shrub in the north.

Its propagation occurs with a heel (in abundance, uninhibited) by seed sown in spring or by greenwood cuttings. It can grow equally well on dry, stony soil in bright sun shine and dapple shade. [8]

Plant Morphology



                            Ashwagandha (Withania somnifera) Plant


Ashwagandha grows as a stout shrub that reaches a height of 2 to 5 feet.



                              Ashwagandha (Withania somnifera) Root

The Root is more or less tuberous, straight, unbranched, conical, buff in color with longitudinal wrinkles. It is grayish from outside and white from inside and 1 to 1.5 feet long. Its odor and flavor is due to some steroidal lactones or Withanolides.


                                 Ashwagandha (Withania somnifera) Stem 

The Stem is small, woody, erect and well branched.



                               Ashwagandha (Withania somnifera) Flowers

The Flowers are sessile, axillary, greenish or lurid yellow flowers. They are hermaphrodite.


                              Ashwagandha (Withania somnifera) Fruits

The Fruit is red, berry-like in size and shape, smooth and in clusters produced at base.


                             Ashwagandha (Withania somnifera) Seeds

The seeds are yellow and scurfy.  [9]

Parts used

Leaves, roots, whole plant.
All parts of the plant are used in herbal medicine.
In Ayurveda, the fresh roots are sometimes boiled in milk, prior to drying, in order to leach out undesirable constituents.

Phytochemistry

All chemicals listed below pertain to the root unless otherwise specified, as the root is the part most commonly used.

The main constituents of Ashwagandhaa (Withania somnifera) are alkaloids and steroidal lactones. Among the various alkaloids, withanine is the main constituent. The other alkaloids are somniferine, somnine, somniferinine, withananine, pseudo-withanine, tropine, pseudo-tropine, 3-a-gloyloxytropane, cuscohygrine, isopelletierine, anaferine and anahydrine.

Two acyl steryl glucoside viz. sitoindoside VII and sitoindoside VIII have been isolated from root.

The leaves contain steroidal lactones, which are commonly called withanolides. The withanolides have C28 steroidal nucleus with C9 side chain, having six membered lactone ring.

The herb also contains monohydric alcohols viz.somnotol and somnorol; a phytosterol and ipuranol and a mixture of fatty acids containing ceroic acid, oleic acid, palmitic acid and stearic acid. 

It is rich in iron and minerals. It also contains withanic acid, choline; beta-sisterol, chlorogenic acid (in leaf only) and cysteine (in fruit).  [10], [11]

Properties and Pharmacology

According to Ayurveda it is Tikta (bitter), Katu (acrid) and general tonic.

It is adaptogen (Rasaayana), aphrodisiac, antiinflammatory, antiviral, hepatoprotective, immunomodulator and antioxidant. It has antitumor, antistress effects. It is nootropic (Medhya=improves intellectual function, memory etc.); lowers high blood pressure.

It is often touted as the Indian version of ginseng because, like ginseng, Ashwagandhaa (Withania somnifera) is revered as an adaptogen that is used alone or as an ingredient in various formulations to treat a variety of conditions.

The plant acts as a libido booster (Wrushya). Withanolides found in Ashwagandhaa (Withania somnifera), appear to have a hormone like effect. They increase activity of hormones like testosterone and progesterone. This could be what is behind Ashwagandhaa (Withania somnifera)'s purported aphrodisiac effects (Waajeekara).

Anti-anxiety, mild sedative and hypnotic action of Ashwagandhaa (Withania somnifera) appears to be due to gamma-amino-butytric acid (GABA) agonist chemicals it contains. As with other herbs, it takes 2 to 4 weeks before you begin to feel its beneficial effects.

The very term Somnifera, suggests Ashwagandhaa (Withania somnifera) produces sedation. Because it balances serotonin levels in the brain (which contribute to the sensitivity of pain receptors in the body), the herb has been shown to relieve pain, including headache.

Ashwagandhaa (Withania somnifera) is reported to have anti-carcinogenic effects in animals and in cell cultures by decreasing the expression of nuclear factor-kappa B, suppressing intercellular tumor necrosis factor, and potentiating apoptotic signaling in cancerous cell lines.

Study of anti tumor and radiosensitizing properties of Ashwagandhaa (Withania somnifera) yielded encouraging results. The alcoholic extract of the dried roots of the plant as well as the active component withaferin- A isolated from the extract showed significant antitumor and radiosensitizing effects in experimental tumors in vivo, without any noticeable systemic toxicity. Though the mechanism of action of this compound is not clearly understood, the studies so far conducted indicate that Ashwagandhaa (Withania somnifera) could prove to be a good natural source of a potent and relatively safe radiosensitizer/chemotherapeutic agent. Further studies in clinical research are needed to explore the potential of this plant for cancer therapy.

Elevation of lipid peroxidation (LPO) was observed in rabbits and mice after intravenous administration of 0.2 μg/kg of lipopolysaccharide (LPS) from Klebsiella pneumoniae and 100 μg/kg of peptidoglycan (PGN) from Staphylococcus aureus, respectively by Jayant N. Dhuley. Simultaneous oral administration of Ashwagandhaa (Withania somnifera) (100 mg/kg) prevented the rise in LPO in rabbits and mice.

Ashwagandhaa (Withania somnifera) was shown to increase swimming time i.e. physical working capacity in rats. In Ashwagandhaa (Withania somnifera) treated group a significant increase in glycogen content in myocardium and liver was observed. Ashwagandhaa (Withania somnifera) (100 mg/kg) counters the toxic action of strophanthin-K. Ashwagandhaa (Withania somnifera) results in significant increase in coagulation time which attains normalcy 7 days after cessation of treatment.

Ashwagandhaa (Withania somnifera) possesses no toxicity up to a dose of (100 mg/kg for 180 days) and does not cause significant changes in biochemical parameters in the blood serum of rats.

Increase in catecholamine content in the heart and aortic tissues and their decrease in adrenal glands are unfavorable effects of high doses of Ashwagandhaa (Withania somnifera). On the basis of these observations, it was concluded that Ashwagandhaa (Withania somnifera) possesses adaptogenic, cardiotropic, cardioprotective and anticoagulant properties.

Ashwagandhaa (Withania somnifera) also relaxes peripheral blood vessels and stimulates circulation.

Pretreatment with Ashwagandhaa (Withania somnifera) prevented gastric ulceration induced chemically or by stress in rats. It prevented increase in adrenal weight and decrease in ascorbic acid and cortisol content of adrenals during stress. It appears to induce a state of non-specifically increased resistance (SNIR) during stress.

Antimicrobial activity

Both aqueous as well as alcoholic extracts of the root as well as leaves were found to possess strong antibacterial activity against a range of bacteria including Salmonella typhimurium. Moreover, in contrast to chloramphenicol, these extracts did not induce lysis on incubation with human erythrocytes, advocating their safety to the living cells.

Extract of the leaves shows activity against Staphylococcus aureus and Ranikhet virus.

A Potent Adaptogen

Having adopted western life style we in east live in a state of stress. Stress is now accepted as a part of lifestyle world over. Stress exerts its profound adverse effects on both our physical body and mental state. To counter and combat stress is a daunting challenge for medical fraternity. Research has been ongoing for decades to counter the ill effects of stress on humans and to discover compounds that will negative its adverse effects and restore physical and mental harmony.

Ashwagandhaa (Withania somnifera) obliges mankind by offering a guerdon of anti- stressor chemicals and potent adaptogens. Ashwagandhaa (Withania somnifera) is widely used in Ayurvedic and Western herbal formulae as an adaptogen.

Worldwide practitioners now believe that adaptogenic herbs and supplements are an important addition to any daily lifestyle modification and dietary supplementation program.

Additional information on Adaptogen

The word adaptogen (wikipedia) is used by herbalists to refer to a natural herb product that increases the body's resistance to stresses such as trauma, anxiety and bodily fatigue. In the past they have been called rejuvenating and disease combating herbs, qi tonics, rasaayanas, or restoratives. All adaptogens contain antioxidants, but antioxidants are not necessarily adaptogens and that is probably not their primary mode of action.

 Wisdom about use of adaptogens in clinical practice dates back thousands of years to ancient India and China. However modern medicine turned Nelson’s eye until the late 1940s. In 1947, Dr. Nikolai Lazarev defined an adaptogen as an agent that allows the body to counter adverse physical, chemical, or biological stressors by raising nonspecific resistance toward such stresses, thus allowing the organism to “adapt” to the stressful circumstances.

Israel I. Brekhman and I. V. Dardymov formally described adaptogens as follows:

1. An adaptogen is nontoxic to the recipient.

2. An adaptogen arouses a nonspecific response in the body and increase resistance against a single or multiple stressors such as physical, chemical or biological agents.

3. An adaptogen has a normalizing influence on physiology, irrespective of the direction of change from physiological norms caused by the stressor.

In simple words adaptogens are nontoxic in normal doses, produce a nonspecific defensive response to stress, and have a normalizing influence on the body. They normalize the hypothalamo- hypophysio-adrenocortical axis (HPA axis). Technically adaptogens constitute a new class of natural, homeostatic metabolic regulators.

It is claimed that adaptogenic herbs act through Psycho-Neuro- Immune (PNI) system and balance the endocrine system and the immune system so as to maintain optimal homeostasis. [12]

Actions on Endocrine System

Adaptogens like Ashwagandhaa (Withania somnifera) exert their actions through endocrine glands like pituitary, thyroid, reproductive glands etc. They balance hormones in the body. 

Ashwagandhaa (Withania somnifera) improves thyroid function especially in hypothyroid subjects. Ashwagandhaa (Withania somnifera) has been shown to correct Hashimoto’s disease and Grave’s disease [13]

Ashwagandhaa (Withania somnifera) has been shown to increase the serum level of DHEA (Dehydroepiandrosterone) sulphate. Ashwagandhaa (Withania somnifera) also increases testosterone level in the blood especially in subfertile males.

An increase in levels of luteinizing hormone has also been observed with Ashwagandhaa (Withania somnifera) supplementation. [14]

Anti-Stressor Activity

In several animal and human studies, Ashwagandhaa (Withania somnifera) has been shown to increase resistance against stress, improve memory-related performance and protect against stress induced adverse responses such as anxiety, and physiological imbalances.

In a comparative study of the anxiolytic and antidepressive actions of Ashwagandhaa (Withania somnifera) with that of benzodiazepine in mice Ashwagandhaa (Withania somnifera) exhibited strong anxiolytic and antidepressive effects.

In another study utilizing rats, the effects of extracts of Ashwagandhaa (Withania somnifera) were compared with those of Asian ginseng (Panax ginseng). Both reduced the number and severity of chronic stress–induced ulcers, reversed the chronic stress–induced inhibition of male sexual behavior, and inhibited the adverse effects of chronic stress.

Sitoindoside VII and sitoindoside VIII have been shown to possess anti-stress activity. [15]

Anti-Aging effects

In a double-blind clinical trial, 101 healthy men aged  between 50 and 59 years received a daily dosage of 3 grams Ashwagandhaa (Withania somnifera)  for 1 year. Significant improvements in hemoglobin, red blood cell counts and hair melanin concentrations, levels of hemoglobin and serum cholesterol concentrations were observed. It was concluded that Ashwagandhaa (Withania somnifera) exhibits anti-aging effects. [16]

Actions on Nervous System

Ashwagandhaa (Withania somnifera) helps calm brain.

In a trial on stressed adult female albino rats were treated with powder of the roots of Ashwagandhaa (Withania somnifera). It significantly reduced (80%) the number of degenerating cells in the hippocampus. It was concluded that Ashwagandhaa (Withania somnifera) has neuroprotective effects. [17], [18]

Modulation of immune response

In a variety of laboratory animals receiving Ashwagandhaa (Withania somnifera) a significant increase of antibody titers to various microbial challenges was observed. The test material also offers direct therapeutic benefits resulting in reduced morbidity and mortality of experimental animals. The study indicates that Ashwagandhaa (Withania somnifera) is a potent immunomodulating agent with possible applications in immunochemical industry. [19]

On Male Reproductive System

Ashwagandhaa (Withania somnifera) improves all parameters in seminal fluid i. e. improves sperm count and sperm motility.

Supplementation of 2g of Ashwagandhaa (Withania somnifera) thrice a day exerts beneficial effect in men with psychogenic ED (erectile dysfunction. [20]

Anti Cancer Activity

 M. S. Cohen, X. Zhang, R. Mukerji, A. K. Samadi; Department of Surgery, University of Kansas Medical Center, Kansas City, studied the effect of WA (Withaferin A) on breast cancer apoptosis through inhibition of estrogen receptor-alpha expression and stimulation of p53 expression. They observed that WA induces breast cancer apoptosis through inhibition of estrogen receptor alpha and induction of p53 expression in vitro. Further studies will evaluate this effect in vivo to validate WA as a promising novel therapeutic agent for breast cancer.

Culinary uses

Seeds used as rennet to coagulate milk.
The berries are used as a substitute for rennet, to coagulate milk in making cheese.
 Ashwagandha Coagulans is a related species and occasional adulterant. The inside kernel of the seed capsule containing "withanin" is similar to rennet and is used to curdle milk.[21]

Medicinal Action and Usages

 It is recommended as a major general tonic for overall good health, to build up and maintain stamina.

In clinical practice Ashwagandhaa (Withania somnifera) has been used to rejuvenate the body, combat illnesses and counter the ravages of ageing. 

As an antitussive, the herb alleviates coughs; as an antiseptic, it fights infection; and as an antispasmodic, it relieves involuntary muscle spasms. The last is particularly valuable when it relives spasms of the lungs, providing relief for bronchitis, asthma and emphysema.

Ashwagandhaa (Withania somnifera) is used to treat insomnia and to produce sedation. It is used as a mild sedative, being especially helpful for those who suffer from insomnia and anxiety. The herb has been shown to relieve pain, including headache.

It has been used to improve cerebral function, including learning ability, memory retention and senile dementia. 

It is used as an aphrodisiac and to treat erectile dysfunction in males.  It is also employed to stimulate sexual capacity and enhance reproductive function in both men and women. It is considered a sexual "grounding" herb which has been used to reduce frequency of premature ejaculation and increase sexual stamina. Its active principles, alkaloids and withanoloids, impart longevity-enhancing and sexually-stimulating properties. Their cumulative sexual effects usually take hold after about a week of daily use.
It is employed to help the body adapt to emotional and physical stress and reinstate the metabolic balance after stressful situations and help the body return to a sense of well-being. 

Ashwagandhaa (Withania somnifera) is considered very useful in treating rheumatoid arthritis. The plant's high steroid content when treated with the herb was found to be a benevolent factor.

Ashwagandhaa (Withania somnifera) is a “bitter” which stimulates the appetite.  When administered to malnourished children as a supplement, increases body weight significantly.

Traditionally, Ashwagandhaa (Withania somnifera) was recommended for indigestion, heart disease, arthritis, lumbar pain, fevers; also used internally for debility, anxiety,  insomnia, improve memory, nervous exhaustion, geriatric complaints, wasting diseases, fibromyalgia, convalescence, joint and nerve pains, multiple sclerosis, rheumatism, sores, boils, senile debility, asthma and  allergic disorders.

Ashwagandhaa (Withania somnifera) is used for hyperacidity, hiccup and chronic liver disorders.
Ashwagandhaa (Withania somnifera) is used to treat impotence and infertility in males and increase sexual desire in men and women.
Ashwagandhaa (Withania somnifera) is used to treat ‘failure to thrive’ in children [22], [23]
                                                                 
Toxicity

CAUTION! Toxic if eaten. Not to be used often.
DRUG INTERACTION: Not to be taken in combination with barbiturates.
CONTRAINDICATED: Not to be used during pregnancy.
It can produce slight nausea. 
Its use can impair sight

Contraindications:
Do not use Ashwagandhaa (Withania somnifera) if you are taking anxiolytics or anti-convulsants. Ashwagandhaa (Withania somnifera) may potentiate the sedative effect of barbiturates. 

Pregnancy, lactation are contraindications for the use of Ashwagandhaa (Withania somnifera).

Ashwagandhaa (Withania somnifera) is contraindicated in leukemia and if the patients are being treated with cyclophosphamide.

Preparations and dosages

Traditional Ayurvedic preparations are: Ashwagandhaa (Withania somnifera)rishta, Ashwagandhaa (Withania somnifera)ghruta, Narayanataila, Balaarishta, saaraswataarishta, Sukumaarghruta.

Recommended Dosage: 100 mg/kg of body weight or up to 3 grams per day taken 2 times daily in boiled warm milk.

Standardized Extract:
One capsule, twice each day at mealtimes.

Botanical Extract: Two capsules, twice a day at mealtimes.
The product called "Ashwagandhaa oil" is a combination of Ashwagandhaa (Withania somnifera) with almond oil and rose water designed to be used as a facial toner, for external use only and hence should not be consumed.  

Infusion: Taken as a tea by simmering 1 part root in 10 parts water for 30 minutes and taken twice daily about 15 to 30 ml at a time.

How to take:

Ashwagandhaa (Withania somnifera) should be taken with meals. If taken in large single dose, once day it should be taken with reakfast

The lowest effective dose for acute usage of Ashwagandhaa (Withania somnifera) is 300-500mg. In special situations it can be administered at a dose of 2g thrice a day. As immunomodulator and anxiolytic agent 50-100 can be effective. [24]


References:

2. https://examine.com/supplements/ashwagandha/
3. www.rxlist.com/ashwagandha/supplements.htm
5. https://examine.com/supplements/ashwagandha/
8. http://archive.allayurveda.com/herb_month_august2011.asp
9. https://en.wikipedia.org/wiki/Withania_somnifera
10. https://en.wikipedia.org/wiki/Withania_somnifera
14. https://examine.com/supplements/ashwagandha/
18. http://www.webmd.com/vitamins-supplements/ingredientmono-953-ashwagandha.aspx?activeingredientid=953
22. https://en.wikipedia.org/wiki/Withania_somnifera
23.http://www.webmd.com/vitamins-supplements/ingredientmono-953-ashwagandha.aspx?activeingredientid=953
24. https://examine.com/supplements/ashwagandha/

 



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