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1Antileishmanial activity in Israeli plants.

El-On J, Ozer L, Gopas J, Sneir R, Enav H, Luft N, Davidov G, Golan-Goldhirsh A.

The Shraga Segal Department of Microbiology and Immunology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel; Laboratory of Parasitology, Soroka University Medical Center, Beer Sheva 84101, Israel.

Leishmaniasis is a vector-borne disease caused by flagellated protozoan parasites of the genus Leishmania, which affects both humans and other mammals. Most of the available drugs against the disease are toxic and parasite resistance to some of the drugs has already developed. In the present study, the leishmanicidal activities of methanolic extracts of some Israeli plants have been evaluated in vitro, against the free-living promastigotes and intracellular amastigotes of Leishmania major. Of the 41 extracts examined, those of two plants (Nuphar lutea>Withania somnifera) were highly effective (with a maximum inhibitory effect of >50%), those of three other species (Pteris vittata>Smyrnium olusatrum>Trifolium clypeatum) were moderately effective (25%-50%) and another four extracts (Erodium malacoides>Hyparrhenia hirta>Thymelaea hirsuta>Pulicaria crispa) showed a marginal effect (15%-22%) against the parasites. Extracts of nine plant species therefore showed antileishmanial activity but only the extract of N. lutea, used at 1.25 mug/ml, eliminated all the intracellular parasites within 3 days of treatment, with no detectable toxicity to the host macrophages. The mean (S.D.) values recorded for the median inhibitory concentrations of this extract (IC(50)) against the promastigotes [2.0 (0.12) mug/ml] and amastigotes [0.65 (0.023) mug/ml] and the median lethal concentration (LD(50)) against macrophages [2.1 (0.096) mug/ml] were encouraging, giving a therapeutic selectivity index [LD(50)/IC(50) for amastigotes)] of 3.23. The extract of N. lutea was, in fact, generally as effective as the paromomycin that was used as the 'gold standard' drug. These results indicate that N. lutea and probably also Withania somnifera might be potential sources of clinically useful, antileishmanial compounds.

PMID: 19508747 [PubMed - in process]


2.In vivo enhancement of natural killer cell activity through tea fortified with Ayurvedic herbs.

Bhat J, Damle A, Vaishnav PP, Albers R, Joshi M, Banerjee G.

Unilever Food and Health Research Institute, Unilever Research India, 64, Main Road, Whitefield, Bangalore 560066, India.

The effect of a tea fortified with five herbs selected from Indian traditional medicine (Ayurveda) for their putative immunoenhancing effect (Withania somnifera, Glycyrrhzia glabra, Zingiber officinale, Ocimum sanctum and Elettaria cardamomum) on innate immunity was investigated. Ex vivo natural killer (NK) cell activity was assessed after consumption of fortified tea compared with regular tea in two independent double-blind intervention studies. Both studies were conducted in India with healthy volunteers (age >/= 55 years) selected for a relatively low baseline NK cell activity and a history of recurrent coughs and colds. In a pilot study conducted with 32 volunteers, the consumption of Natural Care tea significantly improved the NK cell activity of the volunteers in comparison with a population consuming regular tea. These results were validated in an independent crossover study with 110 volunteers. Data from these two studies indicate that regular consumption of the tea fortified with Ayurvedic herbs enhanced NK cell activity, which is an important aspect of the (early) innate immune response to infections. Copyright (c) 2009 John Wiley & Sons, Ltd.

PMID: 19504465 [PubMed - as supplied by publisher]

3.Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males.

Ahmad MK, Mahdi AA, Shukla KK, Islam N, Rajender S, Madhukar D, Shankhwar SN, Ahmad S.

Departmentsof Biochemistry, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India.

OBJECTIVE: To investigate the impact of Withania somnifera roots on semen profile, oxidative biomarkers, and reproductive hormone levels of infertile men. DESIGN: Prospective study. SETTING: Departments of Biochemistry and Urology, Chhatrapati Shahuji Maharaj Medical University, Lucknow, India. PATIENT(S): Seventy-five normal healthy fertile men (control subjects) and 75 men undergoing infertility screening. INTERVENTION(S): High-performance liquid chromatography assay procedure for quantization of vitamin A and E in seminal plasma. Biochemical parameters in seminal plasma were estimated by standard spectrophotometric procedures. Estimation of T, LH, FSH, and PRL in blood serum by RIA methods. MAIN OUTCOME MEASURES(S): Before and after the treatment, seminal plasma biochemical parameters, antioxidant vitamins, and serum T, LH, FSH, and PRL levels were measured. RESULT(S): Withania somnifera inhibited lipid peroxidation and protein carbonyl content and improved sperm count and motility. Treatment of infertile men recovered the seminal plasma levels of antioxidant enzymes and vitamins A, C, and E and corrected fructose. Moreover, treatment also significantly increased serum T and LH and reduced the levels of FSH and PRL. CONCLUSION(S): The treatment with W. somnifera effectively reduced oxidative stress, as assessed by decreased levels of various oxidants and improved level of diverse antioxidants. Moreover, the levels of T, LH, FSH and PRL, good indicators of semen quality, were also reversed in infertile subjects after treatment with the herbal preparation.

PMID: 19501822 [PubMed - as supplied by publisher]


4. Glycowithanolides accumulation in in vitro shoot cultures of Indian ginseng (Withania somnifera Dunal).

Ahuja A, Kaur D, Sharada M, Kumar A, Suri KA, Dutt P.

Indian Institute of Integrative Medicine (CSIR), Jammu 180 001, India. ashoksahuja@rediffmail.com

Phytochemical investigations of multiple shoot cultures of selected accessions AGB002 and AGB025 of Withania somnifera established in vitro utilizing shoot tip apices cultured on Murashige and Skoog's medium supplemented with BAP (1 mg/L) have been carried out. This has lead to isolation of four glycowithanolides viz. Withanoside IV (WSG-3), Withanoside VI (WSG-3A), Physagulin D (WSG-P) and Withastraronolide (WSC-O). The structures of these have been confirmed on the basis of spectroscopic data. Multiple shoot cultures could be an alternative renewable resource for production of these biologically active molecules.

PMID: 19475989 [PubMed - in process]


5. Anticancer Properties of Highly Purified L: -Asparaginase from Withania somnifera L. against Acute Lymphoblastic Leukemia.

Oza VP, Parmar PP, Kumar S, Subramanian RB.

Department of Plant Biotechnology, BRD School of Biosciences, Sardar Patel University, Sardar Patel Maidan, Vadtal Road, Satellite Campus, Post Box No. 39, Vallabh Vidyanagar, 388 120, Gujarat, India.

Withania somnifera L. has been traditionally used as a sedative and hypnotic. The present study was carried out for the purification, characterization, and in vitro cytotoxicity of L: -asparaginase from W. somnifera L. L: -Asparaginase was purified from the fruits of W. somnifera L. up to 95% through chromatography. The purified L: -asparaginase was characterized by size exclusion chromatography, polyacrylamide gel electrophoresis (PAGE), and 2D PAGE. The antitumor and growth inhibition effect of the L: -asparaginase was assessed using [3-(4, 5-dimethyl-thiazol-2yl)-2, 5-diphenyl-tetrazolium bromide] (MTT) colorimetric dye reduction method. The purified enzyme is a homodimer, with a molecular mass of 72 +/- 0.5 kDa, and the pI value of the enzyme was around 5.1. This is the first report of the plant containing L: -asparaginase with antitumor activity. Data obtained from the MTT assay showed a LD(50) value of 1.45 +/- 0.05 IU/ml. W. somnifera L. proved to be an effective and a novel source of L: -asparaginase. Furthermore, it shows a lot of similarity with bacterial L: -asparaginases EC-2.

PMID: 19448978 [PubMed - as supplied by publisher]


6.Neuroprotective Effects of Withania somnifera Dunal.: A Possible Mechanism.

Bhatnagar M, Sharma D, Salvi M.

M.L. Sukhadia University, Udaipur, 313001, India, m.maheep@gmail.com.

Present study was carried out to understand the possible mechanism of neuroprotective action of the root extract of Withania somnifera Dunal (WS). The study is focused on WS mediated inhibition of nitric oxide production, which is known to mediate neurodegeneration during stress. Adult mice (28 +/- 5 g) were exposed to restraint stress for 30 days. Activity of NADPH diaphorase (NADPH-d) and factors (Acetylcholine, serotonin and corticosterone), which regulates NADPH-d activity were studied. Treatment with WS extract for 30 days during stress, significantly reversed the stress induced NADPH-d activation. Observations suggest that inhibition of NADPH-d by WS is not a direct effect of extract on NADPH-d, instead it inhibits via suppressing corticosterone release and activating cholineacetyltransferase, which in turn increase serotonin level in hippocampus to inhibit NADPH-d. Together, the main mechanism underlying the neuroprotective effects of WS can be attributed to its role in the down regulation of nNOS and neurochemical alterations of specific neurotransmitter systems. These observations thus suggest that WS root extract could be developed as a potential preventive or therapeutic drug for stress induced neurological disorders.

PMID: 19444606 [PubMed - as supplied by publisher]


7.Improvement of balance in progressive degenerative cerebellar ataxias after Ayurvedic therapy: A preliminary report.

Sriranjini SJ, Pal PK, Devidas KV, Ganpathy S.

Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, India. pal.pramod@rediffmail.com.

Background: The treatment options for improving the balance in degenerative cerebellar ataxias are very few. Ayurvedic texts have described diverse treatment regimens for this disease. Aims: To determine the change in balance indices, if any, by dynamic posturography (Biodex Balance System, USA) in progressive cerebellar ataxia following Ayurvedic treatment. Materials and Methods: We performed a preliminary open labelled study on ten patients diagnosed with progressive cerebellar ataxia. The patients were treated over a period of one month. Treatment consisted of Shirobasti (therapeutic retention of medicament over the scalp) in male patients and Shirodhara (pouring of a steady stream of medicament on the forehead) in female patients with Dhanvantaram tailam (medicated oil) for 45 minutes daily, followed by Abhyanga (methodical massage) with Dhanvantaram tailam and Bhashpa sweda (steam bath), for 14 days. In addition, the treatment also consisted Abhyantara aushadha (oral medicines) of Maharasnadi kashayam 15ml thrice daily, Dhanvantaram capsules 101 two capsules thrice daily, and Ashwagandha tablet 500 mg one tablet thrice daily, for one month. The patients were assessed on the Biodex balance system before and after the treatment. Results were analyzed using paired samples 't' test. Results: All patients tolerated the treatment well without any adverse events and reported subjective improvement in walking. There was a statistically significant improvement in the overall and anteroposterior balance indices of dynamic stability. Conclusions: Over the short period of the present study, Ayurvedic therapy was found to be safe and, showed improvement in the balance in patients with progressive degenerative cerebellar ataxia. Further randomized placebo-control double-blind studies are needed to validate the results.

PMID: 19439847 [PubMed - in process]


8. Inhibition of NFkappaB by the natural product Withaferin A in cellular models of Cystic Fibrosis inflammation.

Maitra R, Porter MA, Huang S, Gilmour BP.

Center for Organic and Medicinal Chemistry, The Research Triangle Institute, Research Triangle Park, NC 27709, USA. rmaitra@rti.org.

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.

PMID: 19439083 [PubMed - in process] PMCID: PMC2689213


9. Ethnopharmacological survey of wild medicinal plants in Showbak, Jordan.

Al-Qura'n S.

Mu'tah University, Faculty of Science, Department of Biology, P.O. Box 26, Mu'tah, Karak, Jordan. salquran2@yahoo.com

Two main research questions are framing this investigation: (1) the main taxa of the medicinal importance value altered the Showbak forest stand and species composition? (2) The most safe species and what are the toxic ones (unsafe). These two research questions are the vital ones to draw a clear image about the wild medicinal plants of this investigated area of Showbak region in Jordan. 79 wild medicinal plant species were investigated in this study which are used in traditional medication for the treatment of various diseases. Most of the locals interviewed dealt with well-known safe medicinal plants such as Aaronsohnia factorovskyi Warb. et Eig., Achillea santolina L., Adiantum capillus-veneris L., Artemisia herba-alba L., Ceratonia siliqua L., Clematis recta L., Herniaria hirsuta L., Malva neglecta Wallr., Rosmarinus officinalis L., Ruta chalepensis L., Salvia triloba L., Sarcopoterium spinosa (L.) Spach., Thymbra capitata (L.) Hof, and Urginea maritima Barker. Many of the wild medicinal plants investigated were toxic and needed to be practiced by practitioners and herbalists rather than the local healers. These plants include Calotropis procera Willd R.Br., Citrullus colocynthis (L.) Sch., Datura stramonium L., Digitalis purpurea L., Ecballium elaterium (L.) A.Rich., Euphorbia helioscopia L., Euphorbia tinctoria Boiss., Glaucium corniculatum (L.) Curt., Hyoscyamus aureus L., Mandragora officinarum L., Nerium oleander L., Ricinus communis L., Solanum nigrum L., Withania somnifera (L.) Dunel. The conservation of medicinal plants and natural resources is becoming increasingly important, so this research is trying to collect information from local population concerning the use of medicinal plants in Showbak; identify the most important specie; determine the relative importance value of the species and calculate the informant consensus factor (ICF) for the medicinal plants. Obtaining results is relied on the interviewee's personal information and the medicinal use of specific plants.

PMID: 19429338 [PubMed - in process]


10. Ashwagandha leaf extract: a potential agent in treating oxidative damage and physiological abnormalities seen in a mouse model of Parkinson's disease.

Rajasankar S, Manivasagam T, Surendran S.

Department of Anatomy, Melmaruvathur Adhi Parasakthi Institute of Medical Sciences, Tamil Nadu, India.

Parkinson's disease (PD) is a neurodegenerative disorder that leads to impairment of balance and coordination. Therapy for the disease is still under investigation. Withania somnifera (A-Extract), a herbal medicine, has been known for a spectrum of health-promoting effects including activation of immune, muscle and neuronal systems. Therefore effect of A-Extract in the mouse model of PD was examined. The midbrain and corpus striatum of PD mouse showed increased levels of superoxide dismutase, catalase and malondialdehyde; and reduced levels of glutathione and glutathione peroxidase compared to the control. Treatment with A-Extract 100mg/kg for 7 days significantly improved all these enzyme levels compared to A-Extract untreated PD mouse brain. In the PD mouse grooming, stride length, movement, rearing were found to be decreased compared to the control. In addition, narrow beam walk and foot slippery errors were increased. Treatment with A-Extract improved all these physiological abnormalities. These data suggests that A-Extract is a potential drug in treating oxidative damage and physiological abnormalities seen in the PD mouse, if documented also in patients with PD.

PMID: 19429045 [PubMed - in process]


11.Caffeine withdrawal retains anticataleptic activity but Withania somnifera withdrawal potentiates haloperidol-induced catalepsy in mice.

Kasture S, Barhate S, Mohan M, Ballero M, Sanna C, Maxia A.

Department of Pharmacology, Mahatma Gandhi Vidyamandir's Pharmacy Collge, Nashik, Maharashtra, India. kasture_sb@hotmail.com

The previous study showed that chronic treatment with Withania somnifera extract (WS) inhibited haloperidol-induced catalepsy. It is suggested that caffeine and WS may be useful adjuvants in pharmacotherapy of Parkinson's disease. There are no studies on the effect of haloperidol on mice withdrawn from caffeine or W. somnifera. We therefore studied the effect of a single administration of standardised WS containing 5.1% total withanolides (WS, 30 or 100 mg kg(-1) i.p.) and/or caffeine (3 mg kg(-1) i.p.) and withdrawal from 6 days treatment with WS and/or caffeine, on haloperidol-induced catalepsy in albino mice. Single administration of both WS and caffeine, used either alone or in combination, significantly inhibited catalepsy. Mice withdrawn from caffeine significantly inhibited haloperidol-induced catalepsy, but mice withdrawn from WS showed increased catalepsy. The study indicated that withdrawal from WS does not retain anticataleptic activity, and caffeine but not WS may be a good adjuvant in pharmacotherapy of Parkinson's disease.

PMID: 19418355 [PubMed - in process]


12. Genetic and withaferin A analysis of Iranian natural populations of Withania somnifera and W. coagulans by RAPD and HPTLC.

Mirjalili MH, Fakhr-Tabatabaei SM, Alizadeh H, Ghassempour A, Mirzajani F.

Department of Horticultural Sciences, Faculty of Agriculture, University of Tehran, Karaj, Iran. mirjalili@ut.ac.ir

For successful conservation and breeding of a medicinal species, it is important to evaluate its genetic diversity as well as its content of phytochemical compounds. The aim of the present study was to investigate the genetic variation of Iranian natural populations of W. somnifera and W. coagulans, using the RAPD (random amplified polymorphic DNA) markers, and their withaferin A content. Using 16 RAPD primers, a total of 282 RAPD bands were achieved. The highest and lowest percentages of polymorphism were observed with primers OPAD-15 (100.0%) and OPC-06 (75.0%), respectively. Cluster analysis of the genotypes was performed based on data from polymorphic RAPD bands, using Dice's similarity coefficient and the UPGMA clustering method. Variations in the RAPD results were found to reflect geographical distribution and genetic factors of the plant populations. The HPTLC analysis of the studied samples revealed the presence of withaferin A in W. coagulans and W. somnifera. Moreover, the concentration of withaferin A had a range from 2.2 to 32.5 microg/g DW and was higher in the aerial part than in the root in all used samples. The results of the present study show that there is a high level of variation in the Iranian natural population of Withania, which is significant for conservation and breeding programs to improve production of withaferin A.

PMID: 19413110 [PubMed - indexed for MEDLINE]


13. In vivo effects of Ashwagandha (Withania somnifera) extract on the activation of lymphocytes.

Mikolai J, Erlandsen A, Murison A, Brown KA, Gregory WL, Raman-Caplan P, Zwickey HL.

Helfgott Research Institute, National College of Natural Medicine, Portland, OR 97239, USA.

OBJECTIVE: This study investigated the immunologic effects of Ashwagandha (Withania somnifera) on four types of immune cells in a human sample to determine the immunologic mechanism. DESIGN: Five (5) participants consumed 6 mL of an Ashwagandha root extract twice daily for 96 hours. Ashwagandha was administered with anupana (whole milk). Peripheral blood samples were collected at 0, 24, and 96 hours and compared for differences in cell surface expression of CD4, CD8, CD19, CD56, and CD69 receptors by flow cytometry. RESULTS: Significant increases were observed in the expression of CD4 on CD3+ T cells after 96 hours. CD56+ NK cells were also activated after 96 hours as evidenced by expression of the CD69 receptor. At 96 hours of use, mean values of receptor expression for all measured receptor types were increased over baseline, indicating that a major change in immune cell activation occurred across the sample. CONCLUSIONS: Effects on immune cell activation with use of Ashwagandha warrant further study.

PMID: 19388865 [PubMed - in process]

14.Immune modulation and apoptosis induction: Two sides of antitumoural activity of a standardised herbal formulation of Withania somnifera.

Malik F, Kumar A, Bhushan S, Mondhe DM, Pal HC, Sharma R, Khajuria A, Singh S, Singh G, Saxena AK, Suri KA, Qazi GN, Singh J.

Division of Pharmacology, Indian Institute of Integrative Medicine (Council of Scientific and Industrial Research), Canal Road, Jammu 180001, India.

Deregulated apoptosis and suppressed tumour reactive immunity render tumour cells to grow amok in the host body. Traditionally used botanicals may offer potential anticancer chemo-immunotherapeutic leads. We report in this study a chemically standardised herbal formulation (WSF) of Withania somnifera possessing anticancer and Th1 immune up-regulatory activities. WSF produced cytotoxicity in a panel of human cancer cell lines in vitro. The molecular mechanism of cell cytotoxicity, IC(50) 48h approximately 20mug/ml, was investigated in HL-60, where it induced apoptosis by activating both intrinsic and extrinsic signalling pathways. It induced early generation of reactive nitrogen and oxygen species (RNOS), thus producing oxidative stress mediated mitochondrial membrane potential (MMP) loss leading to the release of cytochrome c, the translocation of Bax to mitochondria and apoptosis-inducing factor to the nuclei. These events paralleled the activation of caspase-9, -3 and PARP cleavage. WSF also activated caspase-8 through enhanced expression of TNF-R1 and DR-4, suggesting also the involvement of extrinsic pathway of apoptosis. WSF at 150mg/kg, i.p., inhibited >50% tumour growth in the mouse tumour models. In tumour-bearing mice, WSF inhibited the expression of pStat-3, with a selective stimulation of Th1 immunity as evidenced by enhanced secretion of IFN-gamma and IL-2. In parallel, it enhanced the proliferation of CD4(+)/CD8(+) and NK cells along with an increased expression of CD40/CD40L/CD80. In addition, WSF also enhanced T cell activation in camptothecin treated tumour-bearing mice. WSF being safe when given orally up to 1500mg/kg to rats for 6 months may be found useful in the management of malignancy by targeting at multiple pathways.

PMID: 19269163 [PubMed - indexed for MEDLINE]


15. Ultrastructure of platelets and fibrin networks of asthmatic mice exposed to selenium and Withania somnifera.

Pretorius E, Oberholzer HM, Vieira WA, Smit E.

Department of Anatomy, University of Pretoria, PO Box 2034, Pretoria, 0001, Gauteng, South Africa, resia.pretorius@up.ac.za.

Platelets and fibrin play an important role in allergic processes, including allergic asthma. The asthmatic BALB/c mouse model was used to induce asthma, and asthmatic mice were treated with the anti-inflammatory plant Withania somnifera, separately and in combination with the antioxidant selenium. Selenium is an important supplement in asthma, because asthmatics may have a selenium deficiency. Hydrocortisone was used as positive control. Results indicate control mice possess major thick fibers, minor thin fibers, and tight round activated platelets with typical pseudopodia formation. Minor fibers of asthmatic mice have a netlike appearance covering the major fibers whereas the platelets form loosely connected, granular aggregates. Hydrocortisone made the fibrin more fragile and platelet morphology changes from a tight activated platelet to a more granular activated platelet, not closely fused to each other. The plant extracts, separately and in combination with selenium did not affect the fragility of the fibrin and reversed the formation of the dense minor netlike layer over the major fibers, and the platelets formed a dense aggregate. Asthmatic mice treated with selenium showed a dense minor fibrin layer; however, the platelets formed a dense aggregate. We conclude that the anti-inflammatory products affect the stability of fibrin networks but not platelet stability (seen with hydrocortisone). Selenium does not affect the stability of the fibrin networks, but affects platelet stability. These results suggests that asthmatic patients should indeed use an antioxidant supplement, e.g. selenium, because it stabilizes activated platelets, together with anti-inflammatory products.

PMID: 19214657 [PubMed - as supplied by publisher]


16. Withania somnifera (Ashwagandha): a novel source of L-asparaginase.

Oza VP, Trivedi SD, Parmar PP, Subramanian RB.

BRD School of Biosciences, Sardar Patel University, V V Nagar (Gujarat), India.

Different parts of plant species belonging to Solanaceae and Fabaceae families were screened for L-asparaginase enzyme (E.C. Among 34 plant species screened for L-asparaginase enzyme, Withania somnifera L. was identified as a potential source of the enzyme on the basis of high specific activity of the enzyme. The enzyme was purified and characterized from W. somnifera, a popular medicinal plant in South East Asia and Southern Europe. Purification was carried out by a combination of protein precipitation with ammonium sulfate as well as Sephadex-gel filtration. The purified enzyme is a homodimer, with a molecular mass of 72 +/- 0.5 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and size exclusion chromatography. The enzyme has a pH optimum of 8.5 and an optimum temperature of 37 degrees C. The Km value for the enzyme is 6.1 x 10(-2) mmol/L. This is the first report for L-asparaginase from W. somnifera, a traditionally used Indian medicinal plant.

PMID: 19200159 [PubMed - indexed for MEDLINE]


17. Effect of Withaferin A on the development and decay of thermotolerance in B16F1 melanoma: a preliminary study.

Kalthur G, Mutalik S, Pathirissery UD.

Division of Reproductive Medicine, Kasturba Medical College, Manipal, India. guru.kalthur@manipal.edu

Protein synthesis inhibitors can suppress the development of thermotolerance in tumor tissues on repeated heating. Withaferin A (WA), isolated from Withania somnifera has cytotoxic and inhibitory action on protein synthesis. In the present investigation, effect of WA on development and decay of thermotolerance in B16F1 melanoma was studied in C57BL mice. Tumors of 10010 mm3 size were subjected to repeated hyperthermia (HT) at 43 degrees C for 30 minutes. WA was injected after first hyperthermia treatment. The tumor response was assessed by calculating the tumor growth delay (GD). The GD increased with increase in time gap between two hyperthermia treatments and was significantly higher (p < 0.05 to p < 0.001) in WA treated groups at all the respective time gaps (except at 0h and 120h) compared to hyperthermia alone group. WA increases the tumor response during repeated hyperthermia by reducing the magnitude of thermotolerance developed and by decreasing the recovery time from thermotolerance.

PMID: 19190033 [PubMed - indexed for MEDLINE]


18.Amelioration of metformin-induced hypothyroidism by Withania somnifera and Bauhinia purpurea extracts in Type 2 diabetic mice.

Jatwa R, Kar A.

Endocrine Research Unit, School of Life Sciences, Devi Ahilya University, Indore, M.P., India-452001.

An investigation was carried out to reveal the possible ameliorative role of two plant extracts on an antidiabetic drug-induced hypothyroidism in Type 2 diabetic animals. Dexamethasone (1.0 mg/kg, i.m.) administration caused hyperglycemia with a parallel increase in renal lipid peroxidation (LPO), relative risk ratio (RR), and the concentrations of serum insulin; total cholesterol (TC); low-density lipoprotein cholesterol (LDL-C); very low-density lipoprotein cholesterol (VLDL-C) and triglycerides (TG). It decreased serum triiodothyronine (T(3)), thyroxine (T(4)) and high-density lipoprotein cholesterol (HDL-C) levels as well as renal superoxide dismutase (SOD); catalase (CAT) and reduced glutathione (GSH) content. Administration with metformin (150 mg/kg, orally) to diabetic animals further reduced circulating T(4) level and caused severe hypothyroidism. It also reduced renal LPO, RR, serum concentrations of insulin; glucose and LDL-C with a parallel increase in cellular antioxidants. While oral administration with either Withania somnifera (1.4 g/kg) or Bauhinia purpurea (2.5 mg/kg) extract along with dexamethasone and metformin elevated the concentrations of circulating T(3) and T(4) to euthyroid level. The plant extracts also corrected RR ratio and serum concentration of lipids. The findings of the present study, for the first time, reveal that the evaluated plant extracts have a potential to ameliorate metformin-induced hypothyroidism in Type 2 diabetic subjects. Copyright (c) 2009 John Wiley & Sons, Ltd.

PMID: 19170137 [PubMed - as supplied by publisher]


19.Withanolide sulfoxide from Aswagandha roots inhibits nuclear transcription factor-kappa-B, cyclooxygenase and tumor cell proliferation.

Mulabagal V, Subbaraju GV, Rao CV, Sivaramakrishna C, Dewitt DL, Holmes D, Sung B, Aggarwal BB, Tsay HS, Nair MG.

Bioactive Natural Products and Phytoceuticals, Department of Horticulture and National Food, Safety and Toxicology Center, Michigan State University, East Lansing, Michigan, USA.

Investigation of the methanol extract of Aswagandha (Withania somnifera) roots for bioactive constituents yielded a novel withanolide sulfoxide compound (1) along with a known withanolide dimer ashwagandhanolide (2) with an S-linkage. The structure of compound 1 was established by extensive NMR and MS experiments. Compound 1 was highly selective in inhibiting cyclooxygenase-2 (COX-2) enzyme by 60% at 100 microm with no activity against COX-1 enzyme. The IC(50) values of compound 1 against human gastric (AGS), breast (MCF-7), central nervous system (SF-268) and colon (HCT-116) cancer cell lines were in the range 0.74-3.63 microm. Both S-containing dimeric withanolides, 1 and 2, completely suppressed TNF-induced NF-kappaB activation when tested at 100 microm. The isolation of a withanolide sulfoxide from W. somnifera roots and its ability to inhibit COX-2 enzyme and to suppress human tumor cell proliferation are reported here for the first time. In addition, this is the first report on the abrogation of TNF-induced NF-kappaB activation for compounds 1 and 2. Copyright (c) 2009 John Wiley & Sons, Ltd.



          PMID: 19152372 [PubMed - as supplied by publisher]


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