Ashwagandha Articles 4

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Monograph. Withania somnifera
            (2004) Download

Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress
         (Bhattacharya and Muruganandam, 2003) Download
Withania somnifera (WS) Dunal is classified in Ayurveda, the ancient Hindu system of medicine, as a rasayana, a group of plant-derived drugs reputed to promote physical and mental health, augment resistance of the body against disease and diverse adverse environmental factors, revitalise the body in debilitated conditions and increase longevity. These attributes are remarkably similar to the properties ascribed to adaptogens like Panax ginseng (PG) in contemporary medicine. As such, the adaptogenic activity of a standardised extract of WS roots was investigated against a rat model of chronic stress (CS). The stress procedure was mild, unpredictable footshock, administered once daily for 21 days to adult male Wistar rats. CS induced significant hyperglycaemia, glucose intolerance, increase in plasma corticosterone levels, gastric ulcerations, male sexual dysfunction, cognitive deficits, immunosuppression and mental depression. These CS induced perturbations were attenuated by WS (25 and 50 mg/kg po) and by PG (100 mg/kg po), administered 1 h before footshock for 21 days. The results indicate that WS, like PG, has significant antistress adaptogenic activity, confirming the clinical use of the plant in Ayurveda.

Immunomodulatory activity of Withania somnifera
            (Davis and Kuttan, 2000) Download
Administration of an extract from the powdered root of the plant Withania somnifera was found to stimulate immunological activity in Babl/c mice. Treatment with five doses of Withania root extract (20 mg/dose/animal; i.p.) was found to enhance the total WBC count (17125 cells/mm(3)) on 10th day. Bone marrow cellularity (27x10(6) cells/femur) as well as alpha-esterase positive cell number (1800/4000 cells) also increased significantly (P<0.001) after the administration of Withania extract. Treatment with Withania extract along with the antigen (SRBC) produced an enhancement in the circulating antibody titre and the number of plaque forming cells (PFC) in the spleen. Maximum number of PFC (985 PFC/10(6) spleen cells) was obtained on the fourth day. Withania extract inhibited delayed type hypersentivity reaction in mice (Mantoux test). Administration of Withania extract also showed an enhancement in phagocytic activity of peritoneal macrophages (76.5 pigmented cells/200) when compared to control (31.5/200 cells) in mice. These results confirm the immunomodulatory activity of W. somnifera extract, which is a known immunomodulator in indigenous medicine.

Inhibition of NFkappaB by the natural product Withaferin A in cellular models of Cystic Fibrosis inflammation
            (Maitra et al., 2009) Download
ABSTRACT: Cystic Fibrosis (CF) is one of the most common autosomal genetic disorders in humans. This disease is caused by mutations within a single gene, coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The phenotypic hallmark of CF is chronic lung infection and associated inflammation from opportunistic microbes such as Pseudomonas aeruginosa (PA), Haemophilus influenzae, and Staphylococcus aureus. This eventually leads to deterioration of lung function and death in most CF patients. Unfortunately, there is no approved therapy for correcting the genetic defect causal to the disease. Hence, controlling inflammation and infection in CF patients are critical to disease management. Accordingly, anti-inflammatory agents and antibiotics are used to manage chronic inflammation and infection in CF patients. However, most of the anti-inflammatory agents in CF have severe limitations due to adverse side effects, and resistance to antibiotics is becoming an even more prominent problem. Thus, new agents that can be used to control chronic inflammation in CF are needed in the absence of a cure for the disease. Activation of the transcription factor NFkappaB through Toll-like receptors (TLR) following bacterial infection is principally involved in regulating lung inflammation in CF. NFkappaB regulates the transcription of several genes that are involved in inflammation, anti-apoptosis and anti-microbial activity, and hyper-activation of this transcription factor leads to a potent inflammatory response. Thus, NFkappaB is a potential anti-inflammatory drug target in CF. Screening of several compounds from natural sources in an in vitro model of CF-related inflammation wherein NFkappaB is activated by filtrates of a clinically isolated strain of PA (PAF) led us to Withaferin A (WFA), a steroidal lactone from the plant Withania Somnifera L. Dunal. Our data demonstrate that WFA blocks PAF-induced activation of NFkappaB as determined using reporter assays, IL-8 measurements and high-content fluorescent imaging of NFkappaB subunit p65 translocation. Since the airways of CF patients can be specifically targeted for delivery of therapeutics, we propose that WFA should be further studied as an anti-inflammatory agent in models of CF related inflammation mediated by NFkappaB.

Steroidal lactones from Withania somnifera, an ancient plant for novel medicine
            (Mirjalili et al., 2009) Download
Withania somnifera, commonly known as Ashwagandha, is an important medicinal plant that has been used in Ayurvedic and indigenous medicine for over 3,000 years. In view of its varied therapeutic potential, it has also been the subject of considerable modern scientific attention. The major chemical constituents of the Withania genus, the withanolides, are a group of naturally occurring C28-steroidal lactone triterpenoids built on an intact or rearranged ergostane framework, in which C-22 and C-26 are appropriately oxidized to form a six-membered lactone ring. In recent years, numerous pharmacological investigations have been carried out into the components of W. somnifera extracts. We present here an overview of the chemical structures of triterpenoid components and their biological activity, focusing on two novel activities, tumor inhibition and antiangiogenic properties of withaferin A and the effects of withanolide A on Alzheimer's disease. The most recent attempts in biotechnological production of withanolides are also discussed.

Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review
            (Mishra et al., 2000) Download
OBJECTIVE: The objective of this paper is to review the literature regarding Withania somnifera (ashwagandha, WS) a commonly used herb in Ayurvedic medicine. Specifically, the literature was reviewed for articles pertaining to chemical properties, therapeutic benefits, and toxicity. DESIGN: This review is in a narrative format and consists of all publications relevant to ashwagandha that were identified by the authors through a systematic search of major computerized medical databases; no statistical pooling of results or evaluation of the quality of the studies was performed due to the widely different methods employed by each study. RESULTS: Studies indicate ashwagandha possesses anti-inflammatory, antitumor, antistress, antioxidant, immunomodulatory, hemopoietic, and rejuvenating properties. It also appears to exert a positive influence on the endocrine, cardiopulmonary, and central nervous systems. The mechanisms of action for these properties are not fully understood. Toxicity studies reveal that ashwagandha appears to be a safe compound. CONCLUSION: Preliminary studies have found various constituents of ashwagandha exhibit a variety of therapeutic effects with little or no associated toxicity. These results are very encouraging and indicate this herb should be studied more extensively to confirm these results and reveal other potential therapeutic effects. Clinical trials using ashwagandha for a variety of conditions should also be conducted.

Hypoglycaemic and hypolipidaemic effects of Withania somnifera root and leaf extracts on alloxan-induced diabetic rats
            (Udayakumar et al., 2009) Download
Withania somnifera is an important medicinal plant, which is used in traditional medicine to cure many diseases. Flavonoids were determined in the extracts of W. somnifera root (WSREt) and leaf (WSLEt). The amounts of total flavonoids found in WSREt and WSLEt were 530 and 520 mg/100 g dry weight (DW), respectively. Hypoglycaemic and hypolipidaemic effects of WSREt and WSLEt were also investigated in alloxan-induced diabetic rats. WSREt and WSLEt and the standard drug glibenclamide were orally administered daily to diabetic rats for eight weeks. After the treatment period, urine sugar, blood glucose, haemoglobin (Hb), glycosylated haemoglobin (HbA1C), liver glycogen, serum and tissues lipids, serum and tissues proteins, liver glucose-6-phosphatase (G6P) and serum enzymes like aspartate transaminase (AST), alanine transaminase (ALT), acid phosphatase (ACP) and alkaline phosphatase (ALP) levels were determined. The levels of urine sugar, blood glucose, HbA1C, G6P, AST, ALT, ACP, ALP, serum lipids except high density lipoprotein-bound cholesterol (HDL-c) and tissues like liver, kidney and heart lipids were significantly (p < 0.05) increased, however Hb, total protein, albumin, albumin:globulin (A:G) ratio, tissues protein and glycogen were significantly (p < 0.05) decreased in alloxan-induced diabetic rats. Treatment of the diabetic rats with WSREt, WSLEt and glibenclamide restored the changes of the above parameters to their normal level after eight weeks of treatment, indicating that WSREt and WSLEt possess hypoglycaemic and hypolipidaemic activities in alloxan-induced diabetes mellitus (DM) rats.

Hypocholesteremic and antioxidant effects of Withania somnifera (Dunal) in hypercholesteremic rats
            (Visavadiya and Narasimhacharya, 2007) Download
Hypocholesteremic and antioxidant effects of Withania somnifera (WS) Dunal (Solanaceae) were investigated in hypercholesteremic male albino rats. When the root powder of WS was added to the diet at 0.75 and 1.5 gm/rat/day, hypercholesteremic animals registered significant decreases in total lipids (-40.54%; -50.69%), cholesterol (-41.58%; -53.01%) and triglycerides (-31.25%; - 44.85%) in plasma. On the other hand, significant increases in plasma HDL-cholesterol levels (+15.10%; +17.71%), HMG-CoA reductase activity (+19.51%; +26.02%) and bile acid content (+24.64%; +30.52%) of liver were noted in these animals. A similar trend was also noted in bile acid (+22.43%;+28.52%), cholesterol (+14.21%; +17.68%) and neutral sterol (+12.40%; +18.85%) excretion in the hypercholesteremic animals with WS administration. Further, a significant decrease in lipid-peroxidation (-35.29%; -36.52%) occurred in WS administered hypercholesteremic animals when compared to their normal counterparts. However, it appeared that WS root powder is also effective in normal subjects for decreasing lipid profiles.

 


References

Bhattacharya, S. K. and A. V. Muruganandam (2003), ‘Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress’, Pharmacol Biochem Behav, 75 (3), 547-55. PubMedID: 12895672
Davis, L. and G. Kuttan (2000), ‘Immunomodulatory activity of Withania somnifera’, J Ethnopharmacol, 71 (1-2), 193-200. PubMedID: 10904163
Maitra, R., et al. (2009), ‘Inhibition of NFkappaB by the natural product Withaferin A in cellular models of Cystic Fibrosis inflammation’, J Inflamm (Lond), 6 15. PubMedID: 19439083
Mirjalili, M. H., et al. (2009), ‘Steroidal lactones from Withania somnifera, an ancient plant for novel medicine’, Molecules, 14 (7), 2373-93. PubMedID: 19633611
Mishra, L. C., B. B. Singh, and S. Dagenais (2000), ‘Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review’, Altern Med Rev, 5 (4), 334-46. PubMedID: 10956379
(2004), ‘Monograph. Withania somnifera’, Altern Med Rev, 9 (2), 211-14. PubMedID: 15253680
Udayakumar, R., et al. (2009), ‘Hypoglycaemic and hypolipidaemic effects of Withania somnifera root and leaf extracts on alloxan-induced diabetic rats’, Int J Mol Sci, 10 (5), 2367-82. PubMedID: 19564954
Visavadiya, N. P. and A. V. Narasimhacharya (2007), ‘Hypocholesteremic and antioxidant effects of Withania somnifera (Dunal) in hypercholesteremic rats’, Phytomedicine, 14 (2-3), 136-42. PubMedID: 16713218