Showing papers on "Withania somnifera published in 2012"
TL;DR: The remarkable therapeutic effect of W. somnifera mediated through up-regulation of liver LRP indicates that targeting the periphery offers a unique mechanism for Aβ clearance and reverses the behavioral deficits and pathology seen in Alzheimer's disease models.
Abstract: A 30-d course of oral administration of a semipurified extract of the root of Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of beta-amyloid peptides (A beta) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer's disease transgenic mice. It was similarly effective in reversing behavioral deficits and plaque load in APPSwInd mice (line J20). The temporal sequence involved an increase in plasma A beta and a decrease in brain A beta monomer after 7 d, indicating increased transport of A beta from the brain to the periphery. Enhanced expression of low-density lipoprotein receptor-related protein (LRP) in brain microvessels and the A beta-degrading protease neprilysin (NEP) occurred 14-21 d after a substantial decrease in brain A beta levels. However, significant increase in liver LRP and NEP occurred much earlier, at 7 d, and were accompanied by a rise in plasma sLRP, a peripheral sink for brain A beta. In WT mice, the extract induced liver, but not brain, LRP and NEP and decreased plasma and brain A beta, indicating that increase in liver LRP and sLRP occurring independent of A beta concentration could result in clearance of A beta. Selective down-regulation of liver LRP, but not NEP, abrogated the therapeutic effects of the extract. The remarkable therapeutic effect of W. somnifera mediated through up-regulation of liver LRP indicates that targeting the periphery offers a unique mechanism for A beta clearance and reverses the behavioral deficits and pathology seen in Alzheimer's disease models.
297 citations
TL;DR: This review provides a decisive insight on the molecular basis of the health-promoting potential of Withaferin A.
182 citations
01 Jan 2012
TL;DR: An attempt has been made in this review paper to explore various dimensions of the drug including phytochemical and pharmacological studies carried out on this drug.
Abstract: Withania somnifera (L) Dunal is a well known Indian medicinal plant widely used in the treatment of many clinical conditions in India. It is an important drug commonly known as Asgand which has been used either single or in combination with other drugs in Unani as well as Ayurvedic system of medicine for centuries. It has been described by Dioscorides (78 AD) in his book “Kitab-ul-Hashaish”. Asgand consists of the roots of Withania somnifera which has various therapeutic actions such as anti-inflammatory (Muhallil-e-Warm), sedative (Musakkin), alterative (Muaddil) and aphrodisiac (Muqawwi-e-Bah). Keeping in view the medicinal properties of Withania somnifera Dunal (Asgand), an attempt has been made in this review paper to explore various dimensions of the drug including phytochemical and pharmacological studies carried out on this drug.
123 citations
TL;DR: In this article, a callus-derived adventitious root culture was used for the enhanced production of withanolides upon chitosan elicitation in a half-strength MS medium.
115 citations
TL;DR: In addition to its antioxidant properties, W. somnifer a exhibited significant antibacterial activities against Gram-negative bacteria, particularly S. typhi.
Abstract: Withania somnifera, also known as ashwagandha, is an important herb in ayurvedic and indigenous medical systems. The present study was designed to evaluate the antioxidant and antibacterial activities of an 80% aqueous methanolic extract of W. somnifera roots (WSREt), fruits (WSFEt) and leaves (WSLEt). Several assays were performed to determine the antioxidant properties of this herb including 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) scavenging activity, ferric reducing antioxidant power (FRAP), ferrous chelation and inhibition of β-carotene bleaching. The values for DPPH, FRAP, ferrous chelation and inhibition of β carotene bleaching for the three types of extracts ranged from 101.73-801.93 μg/ml, 2.26-3.29 mM Fe/kg, 0.22-0.65 mg/ml and 69.87-79.67%, respectively, indicating that W. somnifera, particularly the leaves, possesses significant antioxidant properties. The mean ascorbic acid content was 20.60-62.60 mg/100 g, and the mean anthocyanin content was 2.86-12.50 mg/100 g. Antibacterial activities were measured using the agar well diffusion method and five pathogenic Gram-negative bacteria: Escherichia coli, Salmonella typhi, Citrobacter freundii, Pseudomonas aeruginosa and Klebsiella pneumoniae. The leaf extracts displayed the highest activity against S. typhi (32.00 ± 0.75 mm zone of inhibition), whereas the lowest activity was against K. pneumoniae (19.00 ± 1.48 mm zone of inhibition). The lowest minimum inhibitory concentration value was 6.25 mg/ml, which was against S. typhi, followed by 12.5 mg/ml against E. coli. In addition to its antioxidant properties, W. somnifer a exhibited significant antibacterial activities against Gram-negative bacteria, particularly S. typhi.
113 citations
TL;DR: It is demonstrated that Wi-A that binds strongly to the selected targets acts as a strong cytotoxic agent both for normal and cancer cells, and Wi-N, on the other hand, has a weak binding to the targets; it showed milder cytotoxicity towards cancer cells and was safe for normal cells.
Abstract: Background and Purpose: Withanolides are naturally occurring chemical compounds. They are secondary metabolites produced via oxidation of steroids and structurally consist of a steroid-backbone bound to a lactone or its derivatives. They are known to protect plants against herbivores and have medicinal value including anti-inflammation, anti-cancer, adaptogenic and anti-oxidant effects. Withaferin A (Wi-A) and Withanone (Wi-N) are two structurally similar withanolides isolated from Withania somnifera, also known as Ashwagandha in Indian Ayurvedic medicine. Ashwagandha alcoholic leaf extract (i-Extract), rich in Wi-N, was shown to kill cancer cells selectively. Furthermore, the two closely related purified phytochemicals, Wi-A and Wi-N, showed differential activity in normal and cancer human cells in vitro and in vivo. We had earlier identified several genes involved in cytotoxicity of i-Extract in human cancer cells by loss-of-function assays using either siRNA or randomized ribozyme library. Methodology/Principal Findings: In the present study, we have employed bioinformatics tools on four genes, i.e., mortalin, p53, p21 and Nrf2, identified by loss-of-function screenings. We examined the docking efficacy of Wi-N and Wi-A to each of the four targets and found that the two closely related phytochemicals have differential binding properties to the selected cellular targets that can potentially instigate differential molecular effects. We validated these findings by undertaking parallel experiments on specific gene responses to either Wi-N or Wi-A in human normal and cancer cells. We demonstrate that Wi-A that binds strongly to the selected targets acts as a strong cytotoxic agent both for normal and cancer cells. Wi-N, on the other hand, has a weak binding to the targets; it showed milder cytotoxicity towards cancer cells and was safe for normal cells. The present molecular docking analyses and experimental evidence revealed important insights to the use of Wi-A and Wi-N for cancer treatment and development of new anti-cancer phytochemical cocktails.
101 citations
TL;DR: This is the first report on the use of elicitation strategy on the significant improvement in withanolides production in the adventitious root cultures of W. somnifera.
Abstract: Adventitious root cultures derived from leaf derived callus of Withania somnifera (L.) Dunal were treated with methyl jasmonate and salicylic acid independently. Biomass accumulation, culture age, elicitation period, and culture duration were optimized for higher withanolides production in the two best-responding varieties collected from Kolli hills (Eastern Ghats) and Cumbum (Western Ghats) of Tamil Nadu, India. Between the two elicitors, salicylic acid (SA) improved the production of major withanolides (withanolide A, withanolide B, withaferin A, and withanone) as well as minor constituents (12-deoxy withastramonolide, withanoside V, and withanoside IV) in the Kolli hills variety. Treatment of root biomass (11.70 g FW) on 30-day-old adventitious root cultures with 150 μM SA for 4 h elicitor exposure period resulted in the production of 64.65 mg g−l dry weight (DW) withanolide A (48-fold), 33.74 mg g−l DW withanolide B (29-fold), 17.47 mg g−l DW withaferin A (20-fold), 42.88 mg g−l DW withanone (37-fold), 5.34 mg g−l DW 12-deoxy withastramonolide (nine fold), 7.23 mg g−l DW withanoside V (seven fold), and 9.45 mg g−l DW withanoside IV (nine fold) after 10 days of elicitation (40th day of culture) when compared to untreated cultures. This is the first report on the use of elicitation strategy on the significant improvement in withanolides production in the adventitious root cultures of W. somnifera.
91 citations
TL;DR: A new conceptual line of biosynthetic load-driven model of relative recruitment of DOXP and MVA pathways for biosynthesis of isoprenoids has been proposed and elucidates significant contribution of DO XP pathway to withanolide biosynthesis.
Abstract: Withanolides are pharmaceutically important C28-phytochemicals produced in most prodigal amounts and diversified forms by Withania somnifera. Metabolic origin of withanolides from triterpenoid pathway intermediates implies that isoprenogenesis could significantly govern withanolide production. In plants, isoprenogenesis occurs via two routes: mevalonate (MVA) pathway in cytosol and non-mevalonate or DOXP/MEP pathway in plastids. We have investigated relative carbon contribution of MVA and DOXP pathways to withanolide biosynthesis in W. somnifera. The quantitative NMR-based biosynthetic study involved tracing of 13C label from 13C1-d-glucose to withaferin A in withanolide producing in vitro microshoot cultures of the plant. Enrichment of 13C abundance at each carbon of withaferin A from 13C1-glucose-fed cultures was monitored by normalization and integration of NMR signal intensities. The pattern of carbon position-specific 13C enrichment of withaferin A was analyzed by a retro-biosynthetic approach using a squalene-intermediated metabolic model of withanolide (withaferin A) biosynthesis. The pattern suggested that both DOXP and MVA pathways of isoprenogenesis were significantly involved in withanolide biosynthesis with their relative contribution on the ratio of 25:75, respectively. The results have been discussed in a new conceptual line of biosynthetic load-driven model of relative recruitment of DOXP and MVA pathways for biosynthesis of isoprenoids.
91 citations
TL;DR: Evidence is provided that down-regulation of the STAT3 signaling pathway mediates withaferin A-induced apoptosis and is associated with a reduction in Janus-activated kinase 2 (JAK2) activity.
79 citations
TL;DR: The structure–activity relationship analysis (SARA) confirmed the importance of the presence of a ∆2-1-oxo-functionality in ring A, a 5β, 6β-epoxy or 5α-chloro-6β-hydroxy grouping in ring B, and nine-carbon side chain with a lactone moiety for cytotoxic activity.
Abstract: As part of our search for bioactive compounds from plant biodiversity, 29 with- anolides were recently isolated from three members of the Solanaceae: Physalis longifolia, Vassobia breviflora, and Withania somnifera. Six derivatives were prepared from these natu- rally occurring withanolides. All compounds were evaluated for in vitro antiproliferative activity against an array of cell lines (melanoma cell lines (B16F10, SKMEL28); human head and neck squamous cell carcinomas (HNSCC) cell lines (JMAR, MDA1986, DR081-1); breast cancer cell line (Hs578T), and non-malignant human cell line (MRC5)). This led to the discovery of 15 withanolides, with IC 50 values in the range of 0.067−17.4 μM, including withaferin A, withaferin A 4,27-diacetate, 27-O-glucopyranosylwithaferin A, withalongolide H, withalongolide C, withalongolide A, withalongolide A 4,27-diacetate, withalongolide A 4,19,27-triacetate, withalongolide B, withalongolide B 4-acetate, withalongolide B 4,19-diacetate, withalongolide D, withalongolide E, withalongolide G, and 2,3-dihydrowith- aferin A 3-O-sulfate. In order to update the growing literature on withanolides and their activ- ities, we summarized the distribution, structural types, and antiproliferative activities for all published withanolides to date. The structure-activity relationship analysis (SARA) con- firmed the importance of the presence of a Δ 2 -1-oxo-functionality in ring A, a 5β,6β-epoxy or 5α-chloro-6β-hydroxy grouping in ring B, and nine-carbon side chain with a lactone moi- ety for cytotoxic activity. Conversely, the SARA indicated that the -OH or -OR groups at C-4, 7, 11, 12, 14, 15, 16, 17, 18, 19, 20, 23, 24, 27, and 28 were not contributors to the observed antiproliferative activity within the systems analyzed.
78 citations
TL;DR: The methanolic extracts of forty species of plants traditionally used in Saudi Arabia for the treatment of a variety of diseases were tested in vitro for their potential anticancer activity on different human cancer cell lines.
Abstract: Many natural products from plants have been identified to exert anticancer activity. It might be expected to be a challenge to look at the Saudi plants in order to discover new sources for new molecules which may have anticancer activity. The methanolic extracts of forty species of plants traditionally used in Saudi Arabia for the treatment of a variety of diseases were tested in vitro for their potential anticancer activity on different human cancer cell lines. The cytotoxic activity of the methanolic extracts of the tested plants were determined using three human cancer cell lines, namely, breast cancer (MCF7), hepatocellular carcinoma (HEPG2), and cervix cancer (HELA) cells. In addition, human normal melanocyte (HFB4) was used as normal nonmalignant cells. Sulforhodamine B colorimetric assay was used to evaluate the in vitro cytotoxic activity of the different extracts. The growth inhibition of 50% (IC(50)) for each extract was calculated from the optical density of treated and untreated cells. Doxorubicin, a broad-spectrum anticancer drug, was used as the positive control. Nine plant extracts were chosen for further fractionation based on their activity and availability. Interesting cytotoxic activity was observed for Hypoestes forskaolii, Withania somnifera, Solanum glabratum, Adenium obesum, Pistacia vera oleoresin, Caralluma quadrangula, Eulophia petersii, Phragmanthera austroarabica, and Asparagus officinalis. Other extracts showed poor activity.
TL;DR: Quantitative RT-PCR analysis showed that squalene synthase (WsSQS) expressed in all tested tissues including roots, stem and leaves with the highest level of expression in leaves, and up-regulated by different signalling components including methyl-jasmonate, salicylic acid and 2, 4-D, which was consistent with the predicted results of WsS QS promoter region.
TL;DR: In this paper, the authors deal with optimization of parameters of hairy root culture of W. somnifera for the production of biomass and withanolide A. (Indian ginseng) is an important medicinal plant which yields pharmaceutically active compounds called withanolides.
TL;DR: It is demonstrated that RA-differentiated C6 and IMR-32 cells, when exposed to glutamate, undergo loss of neural network and cell death that was accompanied by increase in the stress protein HSP70, and analysis on the neuronal plasticity marker NCAM revealed that ASH-WEX has therapeutic potential for prevention of neurodegeneration associated with glutamate-induced excitotoxicty.
Abstract: Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple sclerosis and neurodegenerative disorders. Search for herbal remedies that may possibly act as therapeutic agents is an active area of research to combat these diseases. The present study was designed to investigate the neuroprotective role of Withania somnifera (Ashwagandha), also known as Indian ginseng, against glutamate induced toxicity in the retinoic acid differentiated rat glioma (C6) and human neuroblastoma (IMR-32) cells. The neuroprotective activity of the Ashwagandha leaves derived water extract (ASH-WEX) was evaluated. Cell viability and the expression of glial and neuronal cell differentiation markers was examined in glutamate challenged differentiated cells with and without the presence of ASH-WEX. We demonstrate that RA-differentiated C6 and IMR-32 cells, when exposed to glutamate, undergo loss of neural network and cell death that was accompanied by increase in the stress protein HSP70. ASH-WEX pre-treatment inhibited glutamate-induced cell death and was able to revert glutamate-induced changes in HSP70 to a large extent. Furthermore, the analysis on the neuronal plasticity marker NCAM (Neural cell adhesion molecule) and its polysialylated form, PSA-NCAM revealed that ASH-WEX has therapeutic potential for prevention of neurodegeneration associated with glutamate-induced excitotoxicty.
Journal Article•
TL;DR: Diseases like TB, chronic upper respiratory diseases and HIV have been added to the list of Ashwagandha due to its strong immunostimulatory activity, and it is recognized as a blood tonic, especially in gynecological disorders including anemia and irregular menstruation.
Abstract: Ashwgandha has long been considered as an excellent rejuvenator, a general health tonic and a cure for a number of health complaints. It is a sedative, diuretic, anti-inflammatory and generally respected for increasing energy, endurance, and acts as an-adaptogen that exerts a strong immunostimulatory and ananti-stress agent. Ashwagandha is taken for treating cold and coughs, ulcers, emaciation, diabetes, conjunctivitis, epilepsy, insomnia, senile dementia, leprosy, Parkinson’s disease, nervous disorders, rheumatism, arthritis, intestinal infections, bronchitis, asthma, impotence and a suppressant in HIV/AIDS patients. According to Indian Herbal System (Ayurveda), Ashwagandha is considered one of the most important herbs and the best adaptogenic. It contains constituents like cuseohygrine, anahygrine, tropine, and anaferine, glycosides, withenolide with starches and amino acid. Withanolide consists of steroidal molecules which is said to fight inflammation.Ashwagandha stimulates the immune system, combats inflammation, increases memory, and helps maintain general health and wellness. Ashwagandha is known to increase the production of bone marrow, semen, and acts anti-aging. Ashwagandha anti-tumor and antiinflammatory agents are approved in several studies. Its steroidal is much higher than that of hydrocortisone which is a common treatment in cancer cases. Diseases like TB, chronic upper respiratory diseases and HIV have been added to the list of Ashwagandha due to its strong immunostimulatory activity, and it is recognized as a blood tonic, especially in gynecological disorders including anemia and irregular menstruation. Patients with anxiety can also benefit from Ashwagandha Keyword: Ashwgandha, Sedative, Diuretic, Cognitive and Neurological Disorders
TL;DR: High-resolution MS and MS/MS experiments provide an extremely effective approach to derive the structures of plant secondary metabolites including isomeric compounds.
Abstract: RATIONALE
Withania somnifera is a rich source of biologically active secondary metabolites. Our earlier investigations on the fruits of this plant have yielded novel compounds, withanamides, with potent antioxidant activity and protective effect on β-amyloid-induced cytotoxicity in vitro. However, several minor compounds present in the fruits have not been characterized previously which may contribute to the observed biological activities.
METHODS
Liquid chromatography (LC) coupled with high-resolution mass spectrometry (HRMS) with data-dependent and targeted MS/MS experiments were conducted to elucidate the structure of observed metabolites.
RESULTS
A total of 62 metabolites identified included 32 withanamides, 22 withanolides, 3 steroidal saponins, 2 lignanamides, feruloyl tyramine, methoxy feruloyl tyramine and a diglucoside of hydroxyl palmitic acid. The structures of these compounds were proposed based on accurate masses of the molecular and fragment ions. Several of these new compounds identified from the profile were derived from withanamides with variations in aliphatic and/or glycosyl moieties. In addition, six new withanolides, a new hydroxy fatty acid diglucoside and several known compounds in the extract were identified.
CONCLUSIONS
The current study revealed the presence of several new and known compounds in Withania somnifera fruits. High-resolution MS and MS/MS experiments provide an extremely effective approach to derive the structures of plant secondary metabolites including isomeric compounds. Copyright © 2012 John Wiley & Sons, Ltd.
TL;DR: It is indicated that WA treatment activates Notch2 and Notch4, which impede inhibitory effect of WA on breast cancer cell migration, and WA-mediated activation of Notch was associated with induction of γ-secretase complex components presenilin1 and/or nicastrin.
Abstract: Ayurvedic medicine plants continue to draw attention for the discovery of novel anticancer agents. Withaferin A (WA) is one such small-molecule constituent of the ayurvedic medicine plant Withania somnifera with efficacy against cultured and xenografted human breast cancer cells. However, the mechanism underlying anticancer effect of WA is not fully understood. This study was undertaken to determine the role of Notch signaling in anticancer effects of WA using human breast cancer cells as a model. Notably, Notch signaling is often hyperactive in human breast cancers. Exposure of MDA-MB-231 and MCF-7 human breast cancer cells to pharmacological concentrations of WA resulted in cleavage (activation) of Notch2 as well as Notch4, which was accompanied by transcriptional activation of Notch as evidenced by RBP-Jk, HES-1A/B, and HEY-1 luciferase reporter assays. On the other hand, WA treatment caused a decrease in levels of both transmembrane and cleaved Notch1. The WA-mediated activation of Notch was associated with induction of γ-secretase complex components presenilin1 and/or nicastrin. Inhibition of MDA-MB-231 and MDA-MB-468 cell migration resulting from WA exposure was significantly augmented by knockdown of Notch2 as well as Notch4 protein. Activation of Notch2 was not observed in cells treated with withanone or withanolide A, which are structural analogs of WA. The results of this study indicate that WA treatment activates Notch2 and Notch4, which impede inhibitory effect of WA on breast cancer cell migration.
TL;DR: It can be concluded that ashwagandha possessed marked anti-inflammatory effect against denaturation of protein in vitro, plausibly due to the alkaloid and withanolide contents of ashwageandha.
TL;DR: Toxicity studies reveal that W. somnifera can be used without side effects, and this herb should be studied more extensively to confirm these results and to reveal other potential therapeutic effects.
Abstract: Withania somnifera (L.) Dunal (Solanaceae), also known as ashwagandha, is an important medicinal plant that is widely used as a home remedy for several diseases in the Indian subcontinent and other parts of the world. W. somnifera is a dietary supplement composed of various nutrients, polyphenols and alkaloids that have free radical scavenging capacity, as well as other chemical constituents that possess anti-inflammatory, antitumor, anti-stress, antioxidant, immunomodulatory, and rejuvenating properties. The mechanism of action for these properties are not fully understood. W. somnifera also appears to influence the endocrine, cardiopulmonary and central nervous systems. Toxicity studies reveal that W. somnifera can be used without side effects. The findings presented in this review are very encouraging and indicate that this herb should be studied more extensively to confirm these results and to reveal other potential therapeutic effects.
TL;DR: This review presents a consolidated account of the phytochemistry, pharmacology and biotechnology involving in vitro propagation, genetic transformation and metabolite profiling in W. somnifera and W. coagulans.
Abstract: Withania (Family: Solanaceae) is a highly acclaimed genus in the Indian Ayurvedic system of medicine. In Ayurveda, Withania is known to promote physical and mental health and used to treat almost all the disorders that affect human health. Withania somnifera andWithania coagulans are the two most esteemed species of this genus having high medicinal significance. These species are natural source of withanolides (steroidal lactones) which are used as ingredients in many formulations prescribed for a variety of diseases. Many pharmacological studies have been conducted to investigate the properties of Withania as a multi-purpose medicinal agent. Advances in biotechnology, especially in vitro culture techniques, molecular biology and metabolite profiling provided new insights for conservation and management of plant genetic resources and better harvesting of drugs from medicinal plants. This review presents a consolidated account of the phytochemistry, pharmacology and biotechnology involving in vitro propagation, genetic transformation and metabolite profiling in W. somnifera and W. coagulans.
Key words: Withania, phytochemistry, pharmacology, withanolides, micropropagation, metabolite profiling.
01 Sep 2012
TL;DR: Botany, chemistry and pharmacology of the plant besides its traditional and folkloric uses are covered, finding it appropriate to develop them as a medicine and make them more potent by chemical modifications and biotransformation.
Abstract: Withania somnifera (L.) Dunal is a well known and important medicinal plant widely used in several indigenous systems of medicine for the treatment of various ailments, viz. asthma, bronchitis, inflammatory diseases, ulcer and stomach problems. Steroidal lactones have been reported as the major phytoconstituents of this species. Different pharmacological experiments in a number of in vitro and in vivo models have convincingly demonstrated the ability of W. somnifera to exhibit anti-inflammatory, anti-oxidative, antimicrobial, anti-anxiety, aphrodisiac, immunomodulation, anti-diabettic, anti-ulcer, anticancer, central nervous system depressant and hepatoprotective activities, lending support to the rationale behind several of its traditional uses. The species is also used to treat some neurological disorders like Parkinson's and Alzheimer's. The molecules such as withaferinA, withanolide A and withanolide D isolated from this plant are potential bioactive molecules. Due to the remarkable biological activity of W. somnifera and its constituents, it will be appropriate to develop them as a medicine and make them more potent by chemical modifications and biotransformation. This review has covered botany, chemistry and pharmacology of the plant besides its traditional and folkloric uses.
01 Jan 2012
TL;DR: In this article, a study was performed to evaluate the phytochemicals and in vitro antioxidant activity of 70% methanolic extract of W. somnifera roots.
Abstract: Withania somnifera, also 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 present study was performed to evaluate the phytochemicals and in vitro antioxidant activity of 70% methanolic extract of W. somnifera roots. The extract was used to determine the antioxidant potential using different tests including total antioxidant activity; efficiencies for scavenging of hydroxyl, superoxide, nitric oxide, singlet oxygen radicals, hypochlorous acid and inhibition of lipid peroxidation. The results obtained indicate that although W. somnifera has been widely used for centuries as immunostimulants in different ailments including neurodegenerative disorders, the 70% methanolic extract of the same also has possibility as an antioxidant and free radical scavenging agent.
TL;DR: An efficient, rapid and improved in vitro plant regeneration protocol has been established for Withania somnifera L. using shoot tip and nodal explants, excised from 15 days old aseptic seedlings with 95 % survival rate.
Abstract: An efficient, rapid and improved in vitro plant regeneration protocol has been established for Withania somnifera L using shoot tip and nodal explants, excised from 15 days old aseptic seedlings A range of cytokinins were investigated for multiple shoot regeneration Of the three cytokinins, 6-benzyladenine (BA), Kinetin (Kin) and 2-isopentenyl adenine (2-iP) evaluated as supplement to Murashige and Skoog (MS) medium, BA at an optimal concentration of 25 μM was most effective in proliferating apical and axillary buds The highest regeneration frequency (95 %) and number of shoots (361 ± 033) were obtained on MS medium fortified with BA (25 μM) and NAA (05 μM) from nodal segments High frequency of rooting (100 %) was obtained in in vitro raised shoots when transferred to half-strength MS medium supplemented with NAA (05 μM) Histological sections revealed that additional shoot bud primordia were differentiated within the explants just underneath the suberized cells which appeared to be arrested in their development The presence of additional bud primordia within the explants is thereby helpful to maximize the potential of this system The regenerated plantlets with well developed shoots and roots were hardened successfully, established in earthen pots containing garden soil and maintained in greenhouse with 95 % survival rate
TL;DR: For W. somnifera the presence of excess calcium in the growing medium is most deleterious compared to other salts, and results suggest that the nonenzymatic and enzymatic antioxidant systems of both the tissues played a primary role in combating the imposed salt stress.
Abstract: In vitro-grown shoots and calli of Withania somnifera, an important medicinal plant, were exposed to various types of salts under in vitro culture conditions. Membrane permeability, lipid peroxidation, and the antioxidant system increased in shoots as well as in unorganized callus tissues under all the three concentrations of KCl, NaCl, KNO3, NaNO3, and CaCl2. The growth responses of shoots and callus cultures under various salt treatments revealed that the tissue could grow better under NaCl and KNO3 compared to other salts and the in vitro shoots appeared healthy at 50 mM concentration of NaCl and KNO3. The activity of antioxidant enzymes such as catalase (CAT), ascorbate peroxidase, guaiacol peroxidase, lipoxygenase, polyphenol oxidase, and glutathione reductase increased under salt treatments, especially at higher concentrations. The greatest activity increase was recorded for peroxidases, whereas CAT was the least responsive. Only two isoforms, Mn-superoxide dismutase (Mn-SOD) and Fe-SOD, could be visualized in callus tissue while Cu/Zn-SOD was absent. Diaphorase 4 was totally missing in callus tissue and was detected only in shoots. Phenolics accumulated at all the concentrations of the salts tested as an induced protective response. The higher concentration of CaCl2 produced maximum increases in antioxidants and enzymatic activities compared to other salts. Thus, for W. somnifera the presence of excess calcium in the growing medium is most deleterious compared to other salts. Results also suggest that the nonenzymatic and enzymatic antioxidant systems of both the tissues played a primary role in combating the imposed salt stress.
TL;DR: In this article, the antimicrobial activity of Withania somnifera and Cenchrus setigerus extracts was investigated in order to use it as a possible source for new antimicrobial substances against important human pathogens.
TL;DR: The tertiary structure of LPKC was modelled and refined using computational methods such as homology modelling and molecular dynamics simulations to reveal mode of inhibition of two previous experimentally reported natural compounds from Withania somnifera.
Abstract: Leishmaniasis is caused by several species of leishmania protozoan and is one of the major vector-born diseases after malaria and sleeping sickness. Toxicity of available drugs and drug resistance development by protozoa in recent years has made Leishmaniasis cure difficult and challenging. This urges the need to discover new antileishmanial-drug targets and antileishmanial-drug development. Tertiary structure of leishmanial protein kinase C was predicted and found stable with a RMSD of 5.8A during MD simulations. Natural compound withaferin A inhibited the predicted protein at its active site with -28.47 kcal/mol binding free energy. Withanone was also found to inhibit LPKC with good binding affinity of -22.57 kcal/mol. Both withaferin A and withanone were found stable within the binding pocket of predicted protein when MD simulations of ligand-bound protein complexes were carried out to examine the consistency of interactions between the two. Leishmanial protein kinase C (LPKC) has been identified as a potential target to develop drugs against Leishmaniasis. We modelled and refined the tertiary structure of LPKC using computational methods such as homology modelling and molecular dynamics simulations. This structure of LPKC was used to reveal mode of inhibition of two previous experimentally reported natural compounds from Withania somnifera - withaferin A and withanone.
TL;DR: Results strongly suggested that administration of W. somnifera through supplementation diet positively enhances the innate immune system and enhanced survival rate in M. rosenbergii against A. hydrophila infection.
TL;DR: The level of expression increased in heat and cold stress indicating the role of sterol modifications in abiotic stress and 3 members of SGT gene family are identified through RACE (Rapid Amplification of cDNA Ends) in addition to sgtl1 reported earlier.
Abstract: Sterol glycosyltransferases (SGTs) catalyze the transfer of sugar molecules to diverse sterol molecules, leading to a change in their participation in cellular metabolism. Withania somnifera is a medicinal plant rich in sterols, sterol glycosides and steroidal lactones. Sterols and their modified counterparts are medicinally important and play a role in adaptation of the plant to stress conditions. We have identified 3 members of SGT gene family through RACE (Rapid Amplification of cDNA Ends) in addition to sgtl1 reported earlier. The amino acid sequence deduced from the ORF's showed homology (45-67 %) to the reported plant SGTs. The expression of the genes was differentially modulated in different organs in W. somnifera and in response to external stimuli. Salicylic acid and methyl jasmonate treatments showed up to 10 fold increase in the expression of sgt genes suggesting their role in defense. The level of expression increased in heat and cold stress indicating the role of sterol modifications in abiotic stress. One of the members, was expressed in E. coli and the enzyme assay showed that the crude enzyme glycosylated stigmasterol. W. somnifera expresses a family of sgt genes and there is a functional recruitment of these genes under stress conditions. The genes which are involved in sterol modification are important in view of medicinal value and understanding stress.
TL;DR: Observations suggest that WS could be developed as a potential preventive drug for ionizing irradiation induced hepatotoxicity disorders via enhancing the antioxidant activity and induction of HO-1.
Journal Article•
TL;DR: Hairy root cultures were induced from leaf explants using Agrobacterium rhizogenes and the transgenic nature of hairy roots was confirmed by partial isolation and sequencing of rolB gene, which could not be amplified in untransformed plant parts.
Abstract: Leaves of Withania somnifera contained more withaferin A and withanolide A than roots indicating that these compounds mainly accumulate in leaves. With an increase in age of the plant, withaferin A was enhanced with a corresponding decrease in withanolide A. Hairy root cultures were induced from leaf explants using Agrobacterium rhizogenes and the transgenic nature of hairy roots was confirmed by partial isolation and sequencing of rolB gene, which could not be amplified in untransformed plant parts. In hairy roots, withaferin A accumulated at 2, 3 and 4% but not at 6% sucrose, the highest amount being 1733 microg/g dry weight at 4% level. High and equal amounts of withaferin A and withanolide A accumulated (890 and 886 microg/g dry tissue respectively) only at 3% sucrose. Increasing concentrations of glucose enhanced withaferin A and it peaked at 5% level (3866 microg/g dry tissue). This amount is 2842 and 34% higher compared to untransformed roots and leaves (collected from 210-day-old plants) respectively. Withanolide A was detected at 5% glucose but not at other concentrations. While chitosan and nitric oxide increased withaferin A, jasmonic acid decreased it. Acetyl salicylic acid stimulated accumulation of both withaferin A and withanolide A at higher concentrations. Triadimefon, a fungicide, enhanced withaferin A by 1626 and 3061% (not detected earlier) compared to hairy and intact roots respectively.