Showing papers on "Withania somnifera published in 2014"
TL;DR: Cancer-protective role for WA has now been established using chemically-induced and oncogene-driven rodent cancer models, and key in vivo preclinical studies demonstrating anticancer effects of WA are summarized.
Abstract: The plants used in Ayurvedic medicine, which has been practiced in India for thousands of years for the treatment of a variety of disorders, are rich in chemicals potentially useful for prevention and treatment of cancer. Withania somnifera (commonly known as Ashwagandha in Ayurvedic medicine) is one such medicinal plant whose anticancer value was realized over four decades ago after isolation of a crystalline steroidal compound (withaferin A) from the leaves of this shrub. The root and leaf extracts of W. somnifera are shown to confer protection against chemically-induced cancers in experimental rodents, and retard tumor xenograft growth in athymic mice. Anticancer effect of W. somnifera is generally attributable to steroidal lactones collectively referred to as withanolides. Withaferin A (WA) appears most active against cancer among structurally divergent withanolides isolated from the root or leaf of W. somnifera. Cancer-protective role for WA has now been established using chemically-induced and oncogene-driven rodent cancer models. This review summarizes the key in vivo preclinical studies demonstrating anticancer effects of WA. Molecular targets and mechanisms likely contributing to the anticancer effects of WA are also discussed. Finally, challenges in clinical development of WA for the prevention and treatment of cancer are highlighted.
99 citations
TL;DR: Various effects and mechanisms of Ashwagandha extracts and related compounds on in vitro and in vivo models of neurodegenerative diseases such as Alzheimer's disease and spinal cord injury are summarized.
Abstract: Neurodegenerative diseases commonly induce irreversible destruction of central nervous system (CNS) neuronal networks, resulting in permanent functional impairments. Effective medications against neurodegenerative diseases are currently lacking. Ashwagandha (roots of Withania somnifera Dunal) is used in traditional Indian medicine (Ayurveda) for general debility, consumption, nervous exhaustion, insomnia, and loss of memory. In this review, we summarize various effects and mechanisms of Ashwagandha extracts and related compounds on in vitro and in vivo models of neurodegenerative diseases such as Alzheimer's disease and spinal cord injury.
96 citations
TL;DR: This optimized protocol can be utilized for commercial level production of withanolides from suspension culture using industrial bioreactors in a short culture period.
Abstract: The present study investigated the biosynthesis of major and minor withanolides of Withania somnifera in cell suspension culture using shake-flask culture and bioreactor by exploiting elicitation and precursor feeding strategies. Elicitors like cadmium chloride, aluminium chloride and chitosan, precursors such as cholesterol, mevalonic acid and squalene were examined. Maximum total withanolides detected [withanolide A (7606.75 mg), withanolide B (4826.05 mg), withaferin A (3732.81 mg), withanone (6538.65 mg), 12 deoxy withanstramonolide (3176.63 mg), withanoside IV (2623.21 mg) and withanoside V (2861.18 mg)] were achieved in the combined treatment of chitosan (100 mg/l) and squalene (6 mM) along with 1 mg/l picloram, 0.5 mg/l KN, 200 mg/l L-glutamine and 5% sucrose in culture at 4 h and 48 h exposure times respectively on 28th day of culture in bioreactor. We obtained higher concentrations of total withanolides in shake-flask culture (2.13-fold) as well as bioreactor (1.66-fold) when compared to control treatments. This optimized protocol can be utilized for commercial level production of withanolides from suspension culture using industrial bioreactors in a short culture period.
81 citations
TL;DR: All five studies concluded that WS intervention resulted in greater score improvements than placebo in outcomes on anxiety or stress scales, and current evidence is received with caution because of an assortment of study methods and cases of potential bias.
Abstract: Objective: To assess existing reported human trials of Withania somnifera (WS; common name, ashwagandha) for the treatment of anxiety. Design: Systematic review of the literature, with searches conducted in PubMed, SCOPUS, CINAHL, and Google Scholar by a medical librarian. Additionally, the reference lists of studies identified in these databases were searched by a research assistant, and queries were conducted in the AYUSH Research Portal. Search terms included “ashwagandha,” “Withania somnifera,” and terms related to anxiety and stress. Inclusion criteria were human randomized controlled trials with a treatment arm that included WS as a remedy for anxiety or stress. The study team members applied inclusion criteria while screening the records by abstract review. Intervention: Treatment with any regimen of WS. Outcome measures: Number and results of studies identified in the review. Results: Sixty-two abstracts were screened; five human trials met inclusion criteria. Three studies compared sever...
77 citations
77 citations
TL;DR: Administration of W. somnifera root powder to the arthritic rats significantly decreased the severity of arthritis by effectively suppressing the symptoms of arthritis and improving the functional recovery of motor activity and radiological score.
Abstract: Context: Withania somnifera (Linn) Dunal (Solanaceae) has long been used as an herb in Ayurvedic and indigenous medicine and has received intense attention in recent years for its chemopreventive propertiesObjective: The present study focuses on the effect of W somnifera root powder on the behavioral and radiological changes in collagen-induced arthritic ratsMaterials and methods: The rats were randomly divided into five groups: normal control, arthritic control, arthritic rats treated with W somnifera root powder (at dose levels 600 and 800 mg kg−1) and arthritic rats treated with methotrexate (at dose level 03 mg kg−1) The treatment with W somnifera (daily) and methotrexate (weekly) was initiated from the 20th day post collagen immunization and continued up until the 45th day Arthritis was assessed macroscopically by measuring paw thickness, ankle size and body weight Arthritic pain was assessed by toe-spread and total print length of the affected paw Functional recovery due to the or
74 citations
TL;DR: It is suggested that Withania somnifera extract can improve cognitive and psychomotor performance and may, therefore, be a valuable adjunct in the treatment of diseases associated with cognitive impairment.
Abstract: Background: Withania somnifera is an herbal medicine that has been known to possess memory-enhancing properties. The current study involved an assessment of cognitive and psychomotor effects of Withania somnifera extract in healthy human participants. Materials and Methods : In this prospective, double-blind, multi-dose, placebo-controlled, crossover study, 20 healthy male participants were randomized to receive 250 mg two capsules twice daily of an encapsulated dried aqueous extract of roots and leaves of Withania somnifera or a matching placebo for a period of 14 days. Cognitive and psychomotor performance was assessed pre-dose (day 1) and at 3 hrs post-dose on day 15 using a battery of computerized psychometric tests. After a washout period of 14 days, the subjects crossed-over to receive the other treatment for a further period of 14 days as per prior randomization schedule. Same battery of test procedures were performed to assess cognitive and psychomotor performance. Results: Significant improvements were observed in reaction times with simple reaction, choice discrimination, digit symbol substitution, digit vigilance, and card sorting tests with Withania somnifera extract compared to placebo. However, no effect can be seen with the finger tapping test. Conclusion: These results suggest that Withania somnifera extract can improve cognitive and psychomotor performance and may, therefore, be a valuable adjunct in the treatment of diseases associated with cognitive impairment.
73 citations
01 Apr 2014
TL;DR: An approach for integration of the available information on several species of medicinal plants used as immunomodulators along with the metabolites responsible for the same has been made in this article.
Abstract: Immunomodulation is the alteration of immune response which may increase or decrease the immune responsiveness. Medicinal plants, since times immemorial, have been used virtually in all cultures as a source of medicine for altering the immune systems. Several medicinal plants have been investigated for immunomodulatory potentials and they are proved to have beneficial effect on alteration of immune system by diverse mechanisms in animals. The present review will provide an up to date knowledge about the medicinal plants used as immunomodulators and their phytoconstituents. This article highlights on the phytochemistry, pharmacology, therapeutic usage and related aspects of 55 medicinal plants, such as Allium sativum, Aloe vera, Andrographis paniculata, Azadirachta indica, Boerhaavia diffusa, Boswellia serrata, Curcuma longa, Centella asiatica, Carica papaya, Datura quercifolia, Emblica officinalis, Hydrastis Canadensis, Hypericum perforatum, Ocimum sanctum, Panax ginseng, Plantago major, Plantago asiatica, Piper longum, Tinospora cordifolia, Mangifera indica, Momordica charantia, Withania somnifera, etc. which have been investigated for their immunomodulatory potentials, and they are proved to acquire beneficial effect on alteration of immune system by diverse mechanisms. Thus an approach for integration of the available information on several species of medicinal plants used as immunomodulators along with the metabolites responsible for the same has been made in this article.
73 citations
TL;DR: Taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer.
Abstract: Withaferin A (WA) isolated from Withania somnifera (Ashwagandha) has recently become an attractive phytochemical under investigation in various preclinical studies for treatment of different cancer types. In the present study, a comparative pathway-based transcriptome analysis was applied in epithelial-like MCF-7 and triple negative mesenchymal MDA-MB-231 breast cancer cells exposed to different concentrations of WA which can be detected systemically in in vivo experiments. Whereas WA treatment demonstrated attenuation of multiple cancer hallmarks, the withanolide analogue Withanone (WN) did not exert any of the described effects at comparable concentrations. Pathway enrichment analysis revealed that WA targets specific cancer processes related to cell death, cell cycle and proliferation, which could be functionally validated by flow cytometry and real-time cell proliferation assays. WA also strongly decreased MDA-MB-231 invasion as determined by single-cell collagen invasion assay. This was further supported by decreased gene expression of extracellular matrix-degrading proteases (uPA, PLAT, ADAM8), cell adhesion molecules (integrins, laminins), pro-inflammatory mediators of the metastasis-promoting tumor microenvironment (TNFSF12, IL6, ANGPTL2, CSF1R) and concomitant increased expression of the validated breast cancer metastasis suppressor gene (BRMS1). In line with the transcriptional changes, nanomolar concentrations of WA significantly decreased protein levels and corresponding activity of uPA in MDA-MB-231 cell supernatant, further supporting its anti-metastatic properties. Finally, hierarchical clustering analysis of 84 chromatin writer-reader-eraser enzymes revealed that WA treatment of invasive mesenchymal MDA-MB-231 cells reprogrammed their transcription levels more similarly towards the pattern observed in non-invasive MCF-7 cells. In conclusion, taking into account that sub-cytotoxic concentrations of WA target multiple metastatic effectors in therapy-resistant triple negative breast cancer, WA-based therapeutic strategies targeting the uPA pathway hold promise for further (pre)clinical development to defeat aggressive metastatic breast cancer.
72 citations
TL;DR: It is suggested that Ws treatment provides nigrostriatal dopaminergic neuroprotection against MB–PQ induced Parkinsonism by the modulation of oxidative stress and apoptotic machinery possibly accounting for the behavioural effects.
Abstract: Maneb (MB) and paraquat (PQ) are environmental toxins that have been experimentally used to induce selective damage of dopaminergic neurons leading to the development of Parkinson’s disease (PD). Although the mechanism of this selective neuronal toxicity in not fully understood, oxidative stress has been linked to the pathogenesis of PD. The present study investigates the mechanisms of neuroprotection elicited by Withania somnifera (Ws), a herb traditionally recognized by the Indian system of medicine, Ayurveda. An ethanolic root extract of Ws was co-treated with the MB–PQ induced mouse model of PD and was shown to significantly rescue canonical indicators of PD including compromised locomotor activity, reduced dopamine in the substantia nigra and various aspects of oxidative damage. In particular, Ws reduced the expression of iNOS, a measure of oxidative stress. Ws also significantly improved the MB + PQ mediated induction of a pro-apoptotic state by reducing Bax and inducing Bcl-2 protein expression, respectively. Finally, Ws reduced expression of the pro-inflammatory marker of astrocyte activation, GFAP. Altogether, the present study suggests that Ws treatment provides nigrostriatal dopaminergic neuroprotection against MB–PQ induced Parkinsonism by the modulation of oxidative stress and apoptotic machinery possibly accounting for the behavioural effects.
70 citations
TL;DR: In vitro shoots could markedly accumulate Cd in a concentration-dependent manner and interplay of enzymatic as well as nonenzymatic responses constituted a system endeavor of tolerance of Cd accumulation and an efficient scavenging strategy of its stress implications.
Abstract: Withania somnifera is one of the most important medicinal plant and is credited with various pharmacological activities. In this study, in vitro multiple shoot cultures were exposed to different concentrations (5–300 μM) of cadmium (Cd) as cadmium sulphate to explore its ability to accumulate the heavy metal ion and its impact on the metabolic status and adaptive responses. The results showed that supplemental exposure to Cd interfered with N, P, and K uptake creating N, P, and K deficiency at higher doses of Cd that also caused stunting of growth, chlorosis, and necrosis. The study showed that in vitro shoots could markedly accumulate Cd in a concentration-dependent manner. Enzymatic activities and isozymic pattern of catalase, ascorbate peroxidase, guaiacol peroxidase, peroxidase, glutathione-S-transferase, glutathione peroxidase, monodehydroascorbate reductase, and dehydroascorbate reductase were altered substantially under Cd exposure. Sugar metabolism was also markedly modulated under Cd stress. Various other parameters including contents of photosynthetic pigments, phenolics, tocopherol, flavonoids, reduced glutathione, nonprotein thiol, ascorbate, and proline displayed major inductive responses reflecting their protective role. The results showed that interplay of enzymatic as well as nonenzymatic responses constituted a system endeavor of tolerance of Cd accumulation and an efficient scavenging strategy of its stress implications.
TL;DR: It is concluded that s-UV-B is a potent factor in increasing the concentrations of secondary metabolites and their biosynthetic pathway enzymes in W. somnifera.
Abstract: The present study aims to investigate the effects of supplemental ultraviolet B (3.6 kJ m(-2)day(-1) above ambient) radiation on secondary metabolites and phenylpropanoid pathway enzymes of Withania somnifera under field conditions at 40, 70, and 100 days after transplantation. Secondary metabolites' (alkaloids, anthocyanins, carotenoids, flavonoids, lignin, phytosterols, saponins, and tannins) concentrations were analysed at the end of the treatments. Activities of phenylalanine ammonia lyase (PAL), cinnamyl alcohol dehydrogenase (CAD), 4-coumarate-CoA ligase (4CL), chalcone-flavanone isomerase (CHI), and dihydroflavonol reductase (DFR) were also determined. In treated plants, secondary metabolite-concentrations generally increased (higher concentrations being recorded in roots compared to leaves). Anomalies were recorded for lycopene in roots and phytosterols in leaves (all sampling ages); β-carotene declined in leaves at third sampling age. s-UV-B-treated plants depicted decrease in withanolide A content with concomitant increase in withaferin A (two major alkaloids analysed by HPLC) compared to their respective controls. Phenylpropanoid pathway enzyme-activities increased in leaves and roots under s-UV-B treatment, the latter showing greater increase. The study concludes that s-UV-B is a potent factor in increasing the concentrations of secondary metabolites and their biosynthetic pathway enzymes in W. somnifera.
TL;DR: Members of OSC superfamily from Withania somnifera, a medicinal plant of immense repute known to synthesize a large array of biologically active steroidal lactone triterpenoids called withanolides, were characterized and negative regulator channelizes substrate pool toward cycloartenol synthase at subdividing junction leading to enhanced withanolide production.
TL;DR: It is hypothesized that Withaferin A kills cancer cells by delaying the mitotic exit followed by inducing chromosome instability.
TL;DR: In this paper, a MTS assay-based antiproliferative evaluation of 95 withanolides was performed on solanaceous species (Datura wrightii, Jaborosa caulescens, Physalis hispida and Physalis longifolia) and revealed that a Δ(2)-1-oxo functionality in ring A, in conjunction with either a 5β, 6β-epoxy or 5α-chloro-6β-hydroxy moiety in ring B, is the minimum structural requirement for withanolide to produce potent cyt
TL;DR: The results indicate that the antimicrobial property of W. somnifera leaf supports the traditional use of the plant in therapeutic use against microbial infections.
Abstract: Background: Withania somnifera is an important medicinal plant that has been used in Ayurvedic and indigenous medicine since ancient times. In the view of its varied therapeutic potential, it has also been the subject of considerable modern scientific attention. Attention has been drawn to antibacterial activity of the plant and its metabolites due to the challenge on growing antibacterial resistant pathogens. Aim: To examine the antimicrobial potential of leaf extract of W. somnifera against Gram-positive cocci. Materials and Methods: In this study, leaf extract of W. somnifera was used to examine their antimicrobial potential against Gram-positive cocci (n = 20) from pus samples of patients admitted in Government Medical College, Haldwani. Agar well diffusion method was used by taking methanolic leaf extract of W. somnifera. Results: It was observed that the methanolic leaf extract of W. somnifera was very effective in inhibiting the test pathogens including methicillin resistant Staphylococcus aureus and Enterococcus spp., with an average zone of inhibition of 20.6 mm and 19.4 mm at 2 mg/ml (100 μl) concentration, respectively. Conclusion: These results indicate that the antimicrobial property of W. somnifera leaf supports the traditional use of the plant in therapeutic use against microbial infections.
TL;DR: In this article, the effects of long term supplemental UV-B (3.6 kJ m−2 d−1) on biomass production, accumulation of reactive oxygen species, lipid peroxidation, and enzymatic antioxidants in leaves and roots of Withania somnifera (an indigenous medicinal plant).
Abstract: The present study was aimed at understanding the effects of long term supplemental UV-B (3.6 kJ m−2 d−1) on biomass production, accumulation of reactive oxygen species, lipid peroxidation, and enzymatic antioxidants in leaves and roots of Withania somnifera (an indigenous medicinal plant). Under the UV-B treatment, a reduction in biomass and an increased malondialdehyde content (a characteristic of lipid peroxidation) were observed in both the shoots and roots. Amongst ROS, H2O2 content increased under UV-B in the leaves, whereas it decreased in the roots, and superoxide radical production rate decreased in both the plant parts. The activities of all enzymatic antioxidants tested (ascorbate peroxidase, catalase, glutathione reductase, peroxidase, polyphenol oxidase, and superoxide dismutase) increased under the UV-B treatment, the increase being greater in the roots.
TL;DR: The transformations of the epoxide group in withanolides of the withaferin A type showed moderate reduction in their cytotoxicity whereas the almost inactive withanones have shown some improvements in their alcohol derivatives.
TL;DR: These herbs were tested for their potential ability to improve climbing ability of a fruit fly in a PD model based on loss of function of phosphatase and tensin‐induced putative kinase 1 (PINK1).
Abstract: Current conventional treatments for Parkinson's disease (PD) are aimed at symptom management, as there is currently no known cure or treatment that can slow down its progression. Ayurveda, the ancient medical system of India, uses a combination of herbs to combat the disease. Herbs commonly used for this purpose are Zandopa (containing Mucuna pruriens), Withania somnifera, Centella asiatica, Sida cordifolia and Bacopa monnieri. In this study, these herbs were tested for their potential ability to improve climbing ability of a fruit fly (Drosophila melanogaster) PD model based on loss of function of phosphatase and tensin-induced putative kinase 1 (PINK1). Fruit flies were cultured on food containing individual herbs or herbal formulations, a combination of all five herbs, levodopa (positive control) or no treatment (negative control). Tests were performed in both PINK1 mutant flies and healthy wild-type (WT) flies. A significant improvement in climbing ability was observed in flies treated with B. monnieri compared with untreated PINK1 mutant flies. However, a significant decrease in climbing ability was observed in WT flies for the same herb. Centella asiatica also significantly decreased climbing ability in WT flies. No significant effects were observed with any of the other herbs in either PINK1 or WT flies compared with untreated flies. Copyright © 2014 John Wiley & Sons, Ltd.
TL;DR: The observed anti-inflammatory activity of TLC separated portion of the supernatant of W. somnifera might be due to rich phenolic acids and flavonoids.
TL;DR: It is suggested that Ashwagandha water extract may have the potential therapeutic implication against lead poisoning.
Abstract: Withania somnifera (Ashwagandha), also known as Indian Ginseng, is a well-known Indian medicinal plant due to its antioxidative, antistress, antigenotoxic, and immunomodulatory properties. The present study was designed to assess and establish the cytoprotective potential of Ashwagandha leaf aqueous extract against lead induced toxicity. Pretreatment of C6 cells with 0.1% Ashwagandha extract showed cytoprotection against 25 μM to 400 μM concentration of lead nitrate. Further pretreatment with Ashwagandha extract to lead nitrate exposed cells (200 μM) resulted in normalization of glial fibrillary acidic protein (GFAP) expression as well as heat shock protein (HSP70), mortalin, and neural cell adhesion molecule (NCAM) expression. Further, the cytoprotective efficacy of Ashwagandha extract was studied in vivo. Administration of Ashwagandha extract provided significant protection to lead induced altered antioxidant defense that may significantly compromise normal cellular function. Ashwagandha also provided a significant protection to lipid peroxidation (LPx) levels, catalase, and superoxide dismutase (SOD) but not reduced glutathione (GSH) contents in brain tissue as well as peripheral organs, liver and kidney, suggesting its ability to act as a free radical scavenger protecting cells against toxic insult. These results, thus, suggest that Ashwagandha water extract may have the potential therapeutic implication against lead poisoning.
TL;DR: The results of the current study indicate that extracts of C. winterianus, V. negundo, and W. somnifera can be used for the control of SP resistant ticks.
Abstract: Detection of resistance levels against cypermethrin and deltamethrin, the most commonly used synthetic pyrethroids (SPs) against Rhipicephalus (Boophilus) microplus collected from Moga, Punjab (India) was carried out using larval packet test. Results indicated the presence of resistance of level I and III against cypermethrin (resistance factors (RF) = 4.67) and deltamethrin (RF = 34.2), respectively. Adult immersion test was used to assess the acaricidal activity of aqueous and ethanolic extracts of leaves of Cymbopogon winterianus, Vitex negundo, and Withania somnifera along with roots of V. negundo against the SP resistant engorged females of R. (B.) microplus. The efficacy of various extracts was assessed by estimation of percent adult mortality, reproductive index (RI), percent inhibition of oviposition (%IO), and hatching rate. A concentration dependent increase in tick mortality was recorded which was more marked with various ethanolic extracts, and highest mortality was recorded in ticks treated with ethanolic extract of leaves of C. winterianus. The LC50 values were determined by applying regression equation analysis to the probit transformed data of mortality for various aqueous and ethanolic extracts. Acaricidal property was recorded to be higher in ethanolic extracts, and high activity was found with the ethanolic extract of leaves of C. winterianus with LC50 (95 % CL) values of 0.46 % (0.35–0.59 %), followed by W. somnifera as 5.21 % (4.45–6.09 %) and V. negundo as 7.02 % (4.58–10.74 %). The egg mass weight of the live ticks treated with different concentrations of the various extract was significantly (p < 0.01) lower than that of control ticks; consequently, the RI and the %IO value of the treated ticks were reduced. Further, complete inhibition of hatching was recorded in eggs laid by ticks treated with ethanolic extracts of leaves of V. negundo and aqueous extracts of leaves of W. somnifera. The results of the current study indicate that extracts of C. winterianus, V. negundo, and W. somnifera can be used for the control of SP resistant ticks.
TL;DR: It is demonstrated that higher glycosylation of sterols and enhanced antioxidant system caused by expression of WsSGTL1 gene confers specific functions in plants to adapt under different environmental challenges.
Abstract: Glycosylation of sterols, catalysed by sterol glycosyltransferases (SGTs), improves the sterol solubility, chemical stability and compartmentalization, and helps plants to adapt to environmental changes. The SGTs in medicinal plants are of particular interest for their role in the biosynthesis of pharmacologically active substances. WsSGTL1, a SGT isolated from Withania somnifera, was expressed and functionally characterized in transgenic tobacco plants. Transgenic WsSGTL1-Nt lines showed an adaptive mechanism through demonstrating late germination, stunted growth, yellowish-green leaves and enhanced antioxidant system. The reduced chlorophyll content and chlorophyll fluorescence with decreased photosynthetic parameters were observed in WsSGTL1-Nt plants. These changes could be due to the enhanced glycosylation by WsSGTL1, as no modulation in chlorophyll biogenesis-related genes was observed in transgenic lines as compared to wildtype (WT) plants. Enhanced accumulation of main sterols like, campesterol, stigmasterol and sitosterol in glycosylated form was observed in WsSGTL1-Nt plants. Apart from these, other secondary metabolites related to plant’s antioxidant system along with activities of antioxidant enzymes (SOD, CAT; two to fourfold) were enhanced in WsSGTL1-Nt as compared to WT. WsSGTL1-Nt plants showed significant resistance towards Spodoptera litura (biotic stress) with up to 27 % reduced larval weight as well as salt stress (abiotic stress) with improved survival capacity of leaf discs. The present study demonstrates that higher glycosylation of sterols and enhanced antioxidant system caused by expression of WsSGTL1 gene confers specific functions in plants to adapt under different environmental challenges.
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Abstract: Glycosylation of sterols, catalysed by sterol glycosyltransferases (SGTs), improves the sterol solubility, chemical stability and compartmentalization, and helps plants to adapt to environmental changes. The SGTs in medicinal plants are of particular interest for their role in the biosynthesis of pharmacologically active substances. WsSGTL1, a SGT isolated from Withania somnifera, was expressed and functionally characterized in transgenic tobacco plants. Transgenic WsSGTL1-Nt lines showed an adaptive mechanism through demonstrating late germination, stunted growth, yellowish-green leaves and enhanced antioxidant system. The reduced chlorophyll content and chlorophyll fluorescence with decreased photosynthetic parameters were observed in WsSGTL1-Nt plants. These changes could be due to the enhanced glycosylation by WsSGTL1, as no modulation in chlorophyll biogenesis-related genes was observed in transgenic lines as compared to wildtype (WT) plants. Enhanced accumulation of main sterols like, campesterol, stigmasterol and sitosterol in glycosylated form was observed in WsSGTL1-Nt plants. Apart from these, other secondary metabolites related to plant’s antioxidant system along with activities of antioxidant enzymes (SOD, CAT; two to fourfold) were enhanced in WsSGTL1-Nt as compared to WT. WsSGTL1-Nt plants showed significant resistance towards Spodoptera litura (biotic stress) with up to 27 % reduced larval weight as well as salt stress (abiotic stress) with improved survival capacity of leaf discs. The present study demonstrates that higher glycosylation of sterols and enhanced antioxidant system caused by expression of WsSGTL1 gene confers specific functions in plants to adapt under different environmental challenges.
TL;DR: This is the first report on expression patterns of PR genes during salicylic acid signaling in W. somnifera.
Abstract: Withania somnifera (L.) Dunal is a valued medicinal plant with pharmaceutical applications. The present study was undertaken to analyze the salicylic acid induced leaf transcriptome of W. somnifera. A total of 45.6 million reads were generated and the de novo assembly yielded 73,523 transcript contig with average transcript contig length of 1620 bp. A total of 71,062 transcripts were annotated and 53,424 of them were assigned GO terms. Mapping of transcript contigs to biological pathways revealed presence of 182 pathways. Seventeen genes representing 12 pathogenesis-related (PR) families were mined from the transcriptome data and their pattern of expression post 17 and 36 hours of salicylic acid treatment was documented. The analysis revealed significant up-regulation of all families of PR genes by 36 hours post treatment except WsPR10. The relative fold expression of transcripts ranged from 1 fold to 6,532 fold. The two families of peroxidases including the lignin-forming anionic peroxidase (WsL-PRX) and suberization-associated anionic peroxidase (WsS-PRX) recorded maximum expression of 377 fold and 6532 fold respectively, while the expression of WsPR10 was down-regulated by 14 fold. Additionally, the most stable reference gene for normalization of qRT-PCR data was also identified. The effect of SA on the accumulation of major secondary metabolites of W. somnifera including withanoside V, withaferin A and withanolide A was also analyzed and an increase in content of all the three metabolites were detected. This is the first report on expression patterns of PR genes during salicylic acid signaling in W. somnifera.
TL;DR: Testing the neuroprotective effects of Methanol: Chloroform (3:1) extract of ASH and its constituent Withanolide A (WA) against Aβ induced toxicity, HIV-1Ba-L (clade B) infection and the effects of drugs of abuse suggests that ASH could be a potential novel drug to reduce the brain amyloid burden and/or improve the HIV- 1 associated neurocognitive impairments.
Abstract: Alzheimer's disease (AD) is characterized by progressive dysfunction of memory and higher cognitive functions with abnormal accumulation of extracellular amyloid plaques and intracellular neurofibrillary tangles throughout cortical and limbic brain regions. Withania somnifera (WS) also known as ‘ashwagandha’ (ASH) is used widely in Ayurvedic medicine as a nerve tonic and memory enhancer. However, there is paucity of data on potential neuroprotective effects of ASH against β-Amyloid (1–42) (Aβ) induced neuropathogenesis. In the present study, we have tested the neuroprotective effects of Methanol: Chloroform (3:1) extract of ASH and its constituent Withanolide A (WA) against Aβ induced toxicity, HIV-1Ba-L (clade B) infection and the effects of drugs of abuse using a human neuronal SK-N-MC cell line. Aβ when tested individually, induced cytotoxic effects in SK-N-MC cells as shown by increased trypan blue stained cells. However, when ASH was added to Aβ treated cells the toxic effects were neutralized. This observation was supported by cellular localization of Aβ, MTT formazan exocytosis, and the levels of acetylcholinesterase activity, confirming the chemopreventive or protective effects of ASH against Aβ induced toxicity. Further, the levels of MAP2 were significantly increased in cells infected with HIV-1Ba-L (clade B) as well as in cells treated with Cocaine (COC) and Methamphetamine (METH) compared with control cells. In ASH treated cells the MAP2 levels were significantly less compared to controls. Similar results were observed in combination experiments. Also, WA, a purified constituent of ASH, showed same pattern using MTT assay as a parameter. These results suggests that neuroprotective properties of ASH observed in the present study may provide some explanation for the ethnopharmacological uses of ASH in traditional medicine for cognitive and other HIV associated neurodegenerative disorders and further ASH could be a potential novel drug to reduce the brain amyloid burden and/or improve the HIV-1 associated neurocognitive impairments
01 Jan 2014
TL;DR: A detailed survey on various traditional uses, phytochemical composition and pharmacological properties of Withania somnifera is presented, considered as similar to Panax ginseng in Chinese medicine.
Abstract: Withania somnifera belongs to the Solanaceae family, commonly known as Ashwagandha, Indian ginseng or Winter cherry. It is an important commercial medicinal crop, considered as similar to Panax ginseng in Chinese medicine. Different parts of this plant are used in traditional medicine for the treatment of various ailments. It provides defense against diseases, adverse environmental factors and helps to retard the aging process. Ashwagandha exhibits a wide range of therapeutic properties by tuning the endocrine, cardiopulmonary, central nervous system and sexual behavior without any toxicity. The root has been used most frequently for therapeutic uses and is a constituent of over 200 formulations in Ayurveda, Siddha and Unani medicines. There are several reports to establish its immunomodulatory, anti-inflammatory, antistress, memory enhancing, antiparkinsonian, hypolipidemic, antibacterial, cardiovascular, antioxidant, antitumor and adaptogenic properties. These properties stem from the characteristic bioactive phytochemicals such as alkaloids and phytosterols present in the plant. This review presents a detailed survey on various traditional uses, phytochemical composition and pharmacological properties of Withania somnifera. INTRODUCTION: Nature is a treasure chest of large diversity of medicinal plants. The search for drugs in nature by man dates from the far past, and this search resulted the evolution of different modern medicinal systems.
TL;DR: The empirical findings suggest that elicitors possibly incite defence or stress responses of the plant by triggering higher accumulation of withanolides in response to elicitations.
Abstract: Pharmacological investigations position withanolides as important bioactive molecules demanding their enhanced production. Therefore, one of the pivotal aims has been to gain knowledge about complete biosynthesis of withanolides in terms of enzymatic and regulatory genes of the pathway. However, the pathway remains elusive at the molecular level. P450s monooxygenases play a crucial role in secondary metabolism and predominantly help in functionalizing molecule core structures including withanolides. In an endeavor towards identification and characterization of different P450s, we here describe molecular cloning, characterization and expression analysis of two A-type P450s, WsCYP98A and WsCYP76A from Withania somnifera. Full length cDNAs of WsCYP98A and WsCYP76A have open reading frames of 1536 and 1545 bp encoding 511 (58.0 kDa) and 515 (58.7 kDa) amino acid residues, respectively. Entire coding sequences of WsCYP98A and WsCYP76A cDNAs were expressed in Escherichia coli BL21 (DE3) using pGEX4T-2 expression vector. Quantitative real-time PCR analysis indicated that both genes express widely in leaves, stalks, roots, flowers and berries with higher expression levels of WsCYP98A in stalks while WsCYP76A transcript levels were more obvious in roots. Further, transcript profiling after methyl jasmonate, salicylic acid, and gibberellic acid elicitations displayed differential transcriptional regulation of WsCYP98A and WsCYP76A. Copious transcript levels of both P450s correlated positively with the higher production of withanolides. Two A-types P450 WsCYP98A and WsCYP76A were isolated, sequenced and heterologously expressed in E. coli. Both P450s are spatially regulated at transcript level showing differential tissue specificity. Exogenous elicitors acted as both positive and negative regulators of mRNA transcripts. Methyl jasmonate and salicylic acid resulted in copious expression of WsCYP98A and WsCYP76A. Enhanced mRNA levels also corroborated well with the increased accumulation of withanolides in response to elicitations. The empirical findings suggest that elicitors possibly incite defence or stress responses of the plant by triggering higher accumulation of withanolides.
TL;DR: In this article, the authors investigated the possible protective role of Withania somnifera (Linn.) Dunal (Solanaceae) root powder against bromobenzene-induced oxidative damage in rat liver mitochondria.
Abstract: The present study investigated the possible protective role of Withania somnifera (Linn.) Dunal (Solanaceae) root powder against bromobenzene-induced oxidative damage in rat liver mitochondria. Administration of bromobenzene (10 mmol/kg body weight) to rats resulted in increased levels of liver marker enzymes, lipid peroxidation, TNF-α, IL-1β and VEGF. There was also marked depletion in the levels of mitochondrial enzymes and antioxidant activity. Pre-treatment with W. somnifera significantly decreased the levels of liver marker enzymes, TNF-α, IL-1β, VEGF and ameliorated histopathological manifestations in bromobenzene-treated rats. The molecular docking analysis predicted that the pro-inflammatory mediator NF-κB showed significant interaction with selected various active components of W. somnifera (withaferin A, withanolide D and withanolide E). This study demonstrates a good protective effect of W. somnifera against bromobenzene-induced oxidative stress.
01 Jan 2014
TL;DR: This chapter provides a glimpse on major secondary metabolites from Ashwagandha, their distribution, occurrence, biosynthesis, genomics, and biotechnology.
Abstract: Ashwagandha is an important traditional medical plant and has been used for more than 3,000 years in Ayurveda and traditional medicine. Ashwagandha is used extensively for pharmacological and medical purposes. Therefore, the plant has attracted scientific attention worldwide. The medicinal properties of Ashwagandha are attributed to specific secondary metabolites such as alkaloids and withsteroids–withanolides. Withanolides are C28 steroidal structures built on an ergostane framework with oxidation at C22 and C26 to form a lactone ring. Withanolides are biosynthesised through the triterpenoid source pathway, and during recent years, tremendous progress in understanding withanolide biosynthesis and genomics has been achieved. This chapter provides a glimpse on major secondary metabolites from Ashwagandha, their distribution, occurrence, biosynthesis, genomics, and biotechnology.