Showing papers on "Withania somnifera published in 2019"
TL;DR: A comprehensive review of the properties of WS extracts (WSE) containing complex mixtures of diverse components including WFA, which have shown inhibitory properties against many cancers, along with their mechanism of actions and pathways involved.
Abstract: Ashwagandha (Withania Somnifera, WS), belonging to the family Solanaceae, is an Ayurvedic herb known worldwide for its numerous beneficial health activities since ancient times. This medicinal plant provides benefits against many human illnesses such as epilepsy, depression, arthritis, diabetes, and palliative effects such as analgesic, rejuvenating, regenerating, and growth-promoting effects. Several clinical trials of the different parts of the herb have demonstrated safety in patients suffering from these diseases. In the last two decades, an active component of Withaferin A (WFA) has shown tremendous cytotoxic activity suggesting its potential as an anti-carcinogenic agent in treatment of several cancers. In spite of enormous progress, a thorough elaboration of the proposed mechanism and mode of action is absent. Herein, we provide a comprehensive review of the properties of WS extracts (WSE) containing complex mixtures of diverse components including WFA, which have shown inhibitory properties against many cancers, (breast, colon, prostate, colon, ovarian, lung, brain), along with their mechanism of actions and pathways involved.
95 citations
TL;DR: These findings suggest that ashwagandha's stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis, and further investigation utilizing larger sample sizes, diverse clinical and cultural populations, and varying treatment dosages are needed to substantiate these findings.
74 citations
TL;DR: It is suggested that Ws significantly ameliorates the level of BPA intoxicated oxidative stress thereby potentially treating cognitive dysfunction which acts as the primary symptom in a number of neurodegenerative diseases.
Abstract: Bisphenol A (BPA), a major endocrine disruptor and a xenobiotic compound is used abundantly in the production of polycarbonate plastics and epoxy resins. Human exposure to this compound is primarily via its leaching from the protective internal epoxy resin coatings of containers into the food and beverages. In addition, the plastics used in dental prostheses and sealants also contain considerable amount of BPA and have a high risk of human exposure. Since it is a well-known endocrine disruptor and closely mimics the molecular structure of human estrogen thereby impairing learning and memory. Withania somnifera (Ws), commonly known as Ashwagandha is known for its varied therapeutic uses in Ayurvedic system of medicine. The present study was undertaken to demonstrate the impairment induced by BPA on the spatial learning, working memory and its alleviation by Ws in Swiss albino mice. The study was conducted on thirty Swiss albino mice, randomly distributed among three groups: control, BPA and BPA + Ws. The behavioral recovery after treatment with Ws was investigated using the Y-maize and Morris water maize test. Whereas, for the estimation of recovery of NMDA receptor which is related to learning and memory in hippocampus region by western blot and immunohistochemistry. Furthermore, the oxidative stress and antioxidant level was assessed by biochemical tests like MDA, SOD and catalase. The study revealed that administration of Ws alleviated the behavioral deficits induced by BPA. Alongside, Ws treatment reinstated the number of NMDA receptors in hippocampus region and showed anti-oxidative property while ameliorating the endogenous anti-oxidant level in the brain. These findings suggest that Ws significantly ameliorates the level of BPA intoxicated oxidative stress thereby potentially treating cognitive dysfunction which acts as the primary symptom in a number of neurodegenerative diseases.
52 citations
TL;DR: Major role of proline and phenylpropanoid metabolism in providing the osmoticum and antioxidants to the plants under Cd stress is elucidated and may be helpful in developing stress resistant plants by targeting these pathways using conventional and molecular approaches.
Abstract: Cadmium (Cd) is considered as a non-essential heavy metal with substantial toxicity on environment. Withania somnifera, a reputed therapeutic herb exhibits vast pharmacological activities due to the presence of steroidal lactones-withanolides. The present study deals with reactive oxygen species (ROS) management through primary and secondary metabolism as adaptive response, on exogenous Cd exposure of W. somnifera. Increased invertase enzyme activity resulted in higher reducing sugars in plant under Cd stress to provide additional carbon source and NADH or NADPH. Higher activities of proline metabolic pathway enzymes such as ornithine aminotransferase (OAT) and pyrroline-5-corboxylate synthase (P5CS) resulted in elevated proline accumulation. The considerable participation of phenylpropanoid metabolism also found dominantly upregulated. Increased enzyme activities of phenylalanine ammonia lyase (PAL), shikimate dehydrogenase (SKDH), glucose-6-phosphate dehydrogenase (G6PDH), and cinnamyl alcohol dehydrogenase (CADH) resulted in phenolics and flavonoids accumulation under higher Cd stress. Upregulation of glutathione-S-transferase (GST) activity conferred its role in Cd chelation. In addition, glutamate oxaloacetate transaminase (GOT), amyl esterase (EST) and diaphorase (DIA) established their participation in Cd tolerance mechanism. Thus, present study elucidated major role of proline and phenylpropanoid metabolism in providing the osmoticum and antioxidants to the plants under Cd stress. The information may be helpful in developing stress resistant plants by targeting these pathways using conventional and molecular approaches.
45 citations
TL;DR: In conclusion, the intake of a standardized ashwagandha extract for 8 weeks was associated with increased levels of DHEA-S and testosterone, although no significant between-group differences were found in cortisol, estradiol, fatigue, vigor, or sexual well-being.
Abstract: Ashwagandha ( Withania somnifera) is a herb commonly used in Ayurvedic medicine to promote youthful vigor, enhance muscle strength and endurance, and improve overall health. In this 16-week, randomized, double-blind, placebo-controlled, crossover study, its effects on fatigue, vigor, and steroid hormones in aging men were investigated. Overweight men aged 40-70 years, with mild fatigue, were given a placebo or an ashwagandha extract (Shoden beads, delivering 21 mg of withanolide glycosides a day) for 8 weeks. Outcome measures included the Profile of Mood States, Short Form (POMS-SF), Aging Males' Symptoms (AMS) questionnaire, and salivary levels of DHEA-S, testosterone, cortisol, and estradiol. Fifty-seven participants were enrolled, with 50 people completing the first 8-week period of the trial and 43 completing all 16 weeks. Improvements in fatigue, vigor, and sexual and psychological well-being were reported over time, with no statistically significant between-group differences. Ashwagandha intake was associated with an 18% greater increase in DHEA-S ( p = .005) and 14.7% greater increase in testosterone ( p = .010) compared to the placebo. There were no significant between-group differences in cortisol and estradiol. In conclusion, the intake of a standardized ashwagandha extract (Shoden beads) for 8 weeks was associated with increased levels of DHEA-S and testosterone, although no significant between-group differences were found in cortisol, estradiol, fatigue, vigor, or sexual well-being. Further studies with larger sample sizes are required to substantiate the current findings.
36 citations
TL;DR: It can be concluded that the use of WSAq300 may be a valuable supplement which can improve human arthritis.
Abstract: Background Rheumatoid Arthritis (RA) is a devastating disease characterized by continual addition of leukocytes and T cells within the articular cavity causing inflammation and cartilage destruction. Withania somnifera is one of the most precious medicinal herbs, reported to have antioxidant, anti-inflammatory, and immunomodulatory properties. Objective The purpose of this study was to evaluate anti-inflammatory activity of aqueous extract of Withania somnifera roots (WSAq) in Collagen Induced Arthritic (CIA) rats. Methods To achieve this, we assessed the level of inflammatory cytokines such as Tumor Necrosis Factor (TNF)-α, IL-1β, IL-6 and IL-10 in CIA rats. Further, transcription factor, oxidative stress parameters and CD+8 expressions were also analyzed in CIA rats. Results Arthritic rats showed a greater increase in the levels of pro inflammatory cytokines such as TNF-α, IL-1β, IL-6, transcription factor NF-κB and a decrease in IL-10 concentration than controls rats. Oral administration of WSAq at a dose of 300mg/kg.wt. (WSAq300) appreciably attenuated the production of these pro inflammatory cytokines. This anti-inflammatory activity of WSAq300 might be partly mediated through an increase in the secretion of IL-10 and inhibition of NF-κB activity. Further, arthritic rats also show increased oxidative stress as compared to control rats. This increased oxidative stress in the arthritic rats appears to be the outcome of both an activated pro-oxidant and a poor antioxidant defense system. Treatment with WSAq300 strongly ameliorates all these ROS parameters significantly to near normal. Additional, metalloproteinase MMP-8 levels were also measured and found to be increased in CIA rats, which after treatment with WSAq300 came down to near normal. Conclusion From the above results, it can be concluded that the use of WSAq300 may be a valuable supplement which can improve human arthritis.
33 citations
TL;DR: Subcritical water extraction can provide effective extraction for ashwagandha withanosides and withanolides compared MAE, SE and MC to conventional methods, which could be used for extraction of pharmacologically active fractions with therapeutic applications.
29 citations
TL;DR: Chemical investigation of the MeOH extract of W. somnifera roots combined with LC/MS-based analysis resulted in the identification of six new withanolides, withasilolides A-F (1-6), as well as seven known compounds (7-13).
Abstract: Withania somnifera, commonly known as “Indian ginseng” or “ashwagandha”, is popular as a functional food because of its diverse purported therapeutic efficacies including invigorating, improvement of cognitive ability, and stress release activities. Chemical investigation of the MeOH extract of W. somnifera roots combined with LC/MS-based analysis resulted in the identification of six new withanolides, withasilolides A–F (1–6), as well as seven known compounds (7–13). The structures of the new compounds were established by application of spectroscopic methods, including 1D and 2D NMR, HRMS, and ECD measurements. The cytotoxicity of the isolated compounds was evaluated against four human cancer cell lines (A549, SK-OV-3, SK-MEL-2, and HCT-15). Compounds 1, 2, 4, 6, and withanone (11) each showed cytotoxicity for one or more of the four cancer cell lines used.
28 citations
TL;DR: This study identified muscarinic receptor as a key target of i-Extract, providing mechanistic evidence for its clinical application in neurodegenerative cognitive disorders.
Abstract: Memory loss is one of the most tragic symptoms of Alzheimer’s disease. Our laboratory has recently demonstrated that ‘i-Extract’ of Ashwagandha (Withania somnifera) restores memory loss in scopolamine (SC)-induced mice. The prime target of i-Extract is obscure. We hypothesize that i-Extract may primarily target muscarinic subtype acetylcholine receptors that regulate memory processes. The present study elucidates key target(s) of i-Extract via cellular, biochemical, and molecular techniques in a relevant amnesia mouse model and primary hippocampal neuronal cultures. Wild type Swiss albino mice were fed i-Extract, and hippocampal cells from naive mice were treated with i-Extract, followed by muscarinic antagonist (dicyclomine) and agonist (pilocarpine) treatments. We measured dendritic formation and growth by immunocytochemistry, kallikrein 8 (KLK8) mRNA by reverse transcription polymerase chain reaction (RT-PCR), and levels of KLK8 and microtubule-associated protein 2, c isoform (MAP2c) proteins by western blotting. We performed muscarinic receptor radioligand binding. i-Extract stimulated an increase in dendrite growth markers, KLK8 and MAP2. Scopolamine-mediated reduction was significantly reversed by i-Extract in mouse cerebral cortex and hippocampus. Our study identified muscarinic receptor as a key target of i-Extract, providing mechanistic evidence for its clinical application in neurodegenerative cognitive disorders.
27 citations
TL;DR: PB125 is a phytochemical dietary supplement comprised of extracts of three ingredients, Rosmarinus officinalis, Withania somnifera, and Sophora japonica, with specified levels of carnosol/carnosic acid, withaferin A, and luteolin, respectively, which leads to upregulation of cytoprotective genes and protection of cells against oxidative stress and supports the use of PB125 as a dietary supplement to promote healthy aging.
Abstract: Bioactive phytochemicals in Rosmarinus officinalis, Withania somnifera, and Sophora japonica have a long history of human use to promote health. In this study we examined the cellular effects of a combination of extracts from these plant sources based on specified levels of their carnosol/carnosic acid, withaferin A, and luteolin levels, respectively. Individually, these bioactive compounds have previously been shown to activate the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, which binds to the antioxidant response element (ARE) and regulates the expression of a wide variety of cytoprotective genes. We found that combinations of these three plant extracts act synergistically to activate the Nrf2 pathway, and we identified an optimized combination of the three agents which we named PB125 for use as a dietary supplement. Using microarray, quantitative reverse transcription-PCR, and RNA-seq technologies, we examined the gene expression induced by PB125 in HepG2 (hepatocellular carcinoma) cells, including canonical Nrf2-regulated genes, noncanonical Nrf2-regulated genes, and genes which appear to be regulated by non-Nrf2 mechanisms. Ingenuity Pathway Analysis identified Nrf2 as the primary pathway for gene expression changes by PB125. Pretreatment with PB125 protected cultured HepG2 cells against an oxidative stress challenge caused by cumene hydroperoxide exposure, by both cell viability and cell injury measurements. In summary, PB125 is a phytochemical dietary supplement comprised of extracts of three ingredients, Rosmarinus officinalis, Withania somnifera, and Sophora japonica, with specified levels of carnosol/carnosic acid, withaferin A, and luteolin, respectively. Each ingredient contributes to the activation of the Nrf2 pathway in unique ways, which leads to upregulation of cytoprotective genes and protection of cells against oxidative stress and supports the use of PB125 as a dietary supplement to promote healthy aging.
26 citations
TL;DR: This extensive study provides first ever pre-clinical evidence that ASH-WEX can be used as a promising natural therapeutic remedial for the prevention of neurodegeneration and cognitive impairments associated with peripheral inflammation and neuroinflammation.
Abstract: Systemic inflammation driven neuroinflammation is an event which correlates with pathogenesis of several neurodegenerative diseases. Therefore, targeting peripheral and central inflammation simultaneously could be a promising approach for the management of these diseases. Nowadays, herbal medicines are emerging as potent therapeutics against various brain pathologies. Therefore, in this contemporary study, the neuroprotective activity of Ashwagandha (Withania somnifera) was elucidated against the inflammation associated neurodegeneration and cognitive impairments induced by systemic LPS administration using in vivo rat model system. To achieve this aim, young adult wistar strain male albino rats were randomized into four groups: (i) Control, (ii) LPS alone, (iii) LPS + ASH-WEX, (iv) ASH-WEX alone. Post regimen, the animals were subjected to Rotarod, Narrow Beam Walking and Novel Object Recognition test to analyze their neuromuscular coordination, working memory and learning functions. The rats were then sacrificed to isolate the brain regions and expression of proteins associated with synaptic plasticity and cell survival was studied using Western blotting and Quantitative real time PCR. Further, neuroprotective potential of ASH-WEX and its active fraction (FIV) against inflammatory neurodegeneration was studied and validated using in vitro model system of microglial conditioned medium–treated neuronal cultures and microglial-neuronal co-cultures. Orally administered ASH-WEX significantly suppressed the cognitive and motor-coordination impairments in rats. On the molecular basis, ASH-WEX supplementation also regulated the expression of various proteins involved in synaptic plasticity and neuronal cell survival. Since microglial-neuronal crosstalk is crucial for maintaining CNS homeostasis, the current study was further extended to ascertain whether LPS–mediated microglial activation caused damage to neurons via direct cell to cell contact or through secretion of inflammatory mediators. ASH-WEX and FIV pretreatment was found to restore neurite outgrowth and protect neurons from apoptotic cell death caused by LPS-induced neuroinflammation in both activated microglial conditioned medium–treated neuronal cultures as well as microglial-neuronal co-cultures. This extensive study using in vivo and in vitro model systems provides first ever pre-clinical evidence that ASH-WEX can be used as a promising natural therapeutic remedial for the prevention of neurodegeneration and cognitive impairments associated with peripheral inflammation and neuroinflammation.
TL;DR: A folate receptor-targeting i-Extract nanocomplex that suspends well in water and possesses enhanced selective anticancer activity in both in vitro and in vivo assays demonstrates that FRi-ExNC could be a natural source-based nanomedicine for targeted cancer therapy.
Abstract: Nanomedicine holds great potential for drug delivery to achieve more effective and safer cancer treatment. Earlier, we reported that the alcoholic extract of Withania somnifera leaves (i-Extract) has selective cancer cell killing activity. Herein, we developed a folate receptor-targeting i-Extract nanocomplex (FRi-ExNC) that suspends well in water and possesses enhanced selective anticancer activity in both in vitro and in vivo assays. Comparative analyses of folate receptor (FR)-positive and -negative cells revealed that FRi-ExNC caused a stronger decrease in Cyclin D/Cdk4 and anti-apoptotic protein Bcl-2, as well as a higher increase in the growth arrest regulating protein p21WAF1 and pro-apoptotic protein PARP-1, in FR-enriched cancer cells. Our results demonstrate that FRi-ExNC could be a natural source-based nanomedicine for targeted cancer therapy.
TL;DR: In this article, W. somnifera plants were grown in vitro and in-vivo and treated with homologous series of Zn-Ag NPs, Ni, and CdSe.
TL;DR: Functional characterization of WsMYC2 via artificial microRNA mediated silencing and transient over-expression displayed significant regulatory role vis-à-vis withanolides and stigmasterol biosyntheses in Withania somnifera, indicating cascading effect on over- expression of multiple pathway genes leading to the increased triterpenoid biosynthesis in infiltered plants.
Abstract: Functional characterization of WsMYC2 via artificial microRNA mediated silencing and transient over-expression displayed significant regulatory role vis-a-vis withanolides and stigmasterol biosyntheses in Withania somnifera. Further, metabolic intensification corroborated well with higher expression levels of putative pathway genes. Additionally, copious expression of WsMYC2 in response to exogenous elicitors resulted in enhanced withanolides production. Withania somnifera, a high value multipurpose medicinal plant, is a rich reservoir of structurally diverse and biologically active triterpenoids known as withanolides. W. somnifera has been extensively pursued vis-a-vis pharmacological and chemical studies. Nonetheless, there exists fragmentary knowledge regarding the metabolic pathway and the regulatory aspects of withanolides biosynthesis. Against this backdrop, a jasmonate-responsive MYC2 transcription factor was identified and functionally characterized from W. somnifera. In planta transient over-expression of WsMYC2 showed significant enhancement of mRNA transcript levels which corroborated well with the enhanced content of withanolides and stigmasterol. Further, a comparative analysis of expression levels of some of the genes of triterpenoid pathway viz. WsCAS, WsCYP85A, WsCYP90B and WsCYP710A in corroboration with the over-expression and silencing of WsMYC2 suggested its positive influence on their regulation. These corroboratory approaches suggest that WsMYC2 has cascading effect on over-expression of multiple pathway genes leading to the increased triterpenoid biosynthesis in infiltered plants. Further, the functional validation of WsMYC2 was carried out by artificial micro-RNA mediated silencing. It resulted in significant reduction of withanolides and stigmasterol levels, indicative of crucial role of WsMYC2 in the regulation of their biosyntheses. Taken together, these non-complementary approaches provided unambiguous understanding of the regulatory role of WsMYC2 in context to withanolides and stigmasterol biosyntheses. Furthermore, the upstream promoter of WsMYC2 presented several cis-regulatory elements primarily related to phytohormone responsiveness. WsMYC2 displayed inducible nature in response to MeJA. It had substantial influence on the higher expression of WsMYC2 which was in consonance with enhanced accumulation of withanolides.
TL;DR: This study is the first report in W. somnifera hairy roots, where the natural polysaccharides are used as elicitors for the large-scale production of WA, and developed an elicitation based on the hairy root culture protocol for the enhancement of the WA production.
Abstract: Withaferin-A (WA) is a major bioactive compound in the roots of Withania somnifera. It is reported to possess inhibitory effects against breast cancer, liver cancer, melanoma cancer and prostate cancer cells. We developed an elicitation based on the hairy root culture (HRC) protocol for the enhancement of the WA production. Agrobacterium rhizogenes strain R1000 was used for the establishment of hairy root culture. PCR analysis confirmed the integration of the root loci C (rol C) gene in transformed roots. Elicitation of the hairy roots with natural polysaccharides of sodium alginate (SA), k-carrageenan (kC) and chitosan (CH) at various concentrations in the most cases resulted in a higher amount of WA compound. Among the various elicitors, 100 mg L−1 CH resulted 4.03-fold increase in WA production than control. This study is the first report in W. somnifera hairy roots, where the natural polysaccharides are used as elicitors for the large-scale production of WA.
TL;DR: WSPF exhibited apoptotic activity for each cancer cell line tested, demonstrating significant activity against MDA-MB-231 human breast cancer cells with an IC50 value of 92 μg/mL, indicating that the proteins in this fraction can be potential therapeutic agents for triple negative breast cancer treatment.
TL;DR: Withania somnifera as a nephroprotective and nephrocurative molecule significantly restore the renal function on gentamicin-induced nephrotoxicity in wistar rats.
Abstract: Gentamicin induced renal complications are well known in humans and animals. Medicinal properties of Withania somnifera (L.) Dunal, Solanaceae, are recognized to improve renal functions. However, the pharmacological function of W. somnifera is not completely understood. We sought to unravel medicinal therapeutic function of W. somnifera on gentamicin-induced nephrotoxicity in wistar rats. Twenty-four adult male wistar rats evenly divided into four groups to evaluate in vivo nephroprotective and nephrocurative function of W. somnifera in gentamicin induced nephrotoxic rats. Experimental design as follows: Group I, saline control for 21 days; Group II, gentamicin nephrotoxic control for eight days; Group III, alcoholic extract of W. somnifera for 13 days + simultaneous administration of gentamicin and W. somnifera, from day 14 to 21 (nephroprotective) and Group IV, gentamicin for 8 days + alcoholic extract of W. somnifera from day 9 to 21 (nephrocurative). End of experiment, respective serum and kidney tissue samples used to analyze renal function. Withania somnifera as a nephroprotective and nephrocurative molecule significantly restore the renal function on gentamicin-induced nephrotoxicity. This phenomenon is accompanied with significantly reduced blood urea nitrogen, creatine, alkaline phosphatase, gamma-glutamyl transferase, albumin, total protein, calcium, potassium and kidney malondialdehyde concentrations. Additionally, W. somnifera significantly increased antioxidant activities of glutathione and superoxide dismutase to protect renal tissue damage from gentamicin in wistar rats. Over all, W. somnifera treated nephroprotective animal shows improved recovery compared to nephrocuartive. The nephroprotective or nephrocurative effect of W. somnifera could be due to inherent antioxidant and free-radical-scavenging principle(s). In the near future, biologically active compounds of W. somnifera (withanolides) could appear as a novel therapeutic molecule for renal disorders.
30 Sep 2019
TL;DR: This article showed that muscarinic subtype acetylcholine receptors that regulate memory processes are a key target of Ashwagandha extract in Alzheimer's disease and showed that i-extract stimulated an increase in dendrite growth markers, including kallikrein 8 and MAP2.
Abstract: Memory loss is one of the most tragic symptoms of Alzheimer’s disease. Our laboratory has recently demonstrated that ‘i-Extract’ of Ashwagandha (Withania somnifera) restores memory loss in scopolamine (SC)-induced mice. The prime target of i-Extract is obscure. We hypothesize that i-Extract may primarily target muscarinic subtype acetylcholine receptors that regulate memory processes. The present study elucidates key target(s) of i-Extract via cellular, biochemical, and molecular techniques in a relevant amnesia mouse model and primary hippocampal neuronal cultures. Wild type Swiss albino mice were fed i-Extract, and hippocampal cells from naive mice were treated with i-Extract, followed by muscarinic antagonist (dicyclomine) and agonist (pilocarpine) treatments. We measured dendritic formation and growth by immunocytochemistry, kallikrein 8 (KLK8) mRNA by reverse transcription polymerase chain reaction (RT-PCR), and levels of KLK8 and microtubule-associated protein 2, c isoform (MAP2c) proteins by western blotting. We performed muscarinic receptor radioligand binding. i-Extract stimulated an increase in dendrite growth markers, KLK8 and MAP2. Scopolamine-mediated reduction was significantly reversed by i-Extract in mouse cerebral cortex and hippocampus. Our study identified muscarinic receptor as a key target of i-Extract, providing mechanistic evidence for its clinical application in neurodegenerative cognitive disorders.
TL;DR: Red light and Violet light enhanced the total phenolic and flavonoid content in callus culture of W. somnifera with lower antioxidant enzymes activities and combination of thidiazuron and naphthalene acetic acid induced callus growth in Withania somNifera.
TL;DR: The crucial role of the ascorbate-glutathione-α-tocopherol triad in co-ordination with withanolide biosynthesis in affording the oxidative stress, possibly through a cross-talk between the antioxidant machinery and secondary metabolite biosynthesis is indicated.
TL;DR: A simple, rapid and selective high-performance thin-layer chromatographic (HPTLC) method has been developed and validated for simultaneous determination of three withanolides and three phenolic acids from different parts of Withania somnifera and its two commercially available polyherbal formulations.
TL;DR: This has been the first report on the potential use of fungi naturally associated with W. somnifera for FCRR suppression and for tomato growth promotion and further investigations are required in regard to mechanisms of action involved in disease suppression and plant growth promotion.
TL;DR: In vivo study showed that, dose-dependent reduction in phagocytosis, an increase in the levels of NO production along with up-regulation of TLR6, arginase gene was significant when ZnO NPs were given, however toxicity of ZnNO NP was reduced in presence of WS and WA with decreased TLR 6 over expression and restoration of phagocytes activities.
Abstract: The current study was undertaken to investigate the immunomodulatory and protective effects of Withania somnifera (WS) extract and Withaferin A (WA) supplementation on zinc oxide nanoparticles mediated toxicity in Balb/c mice. The animals were exposed to ZnO NPs along with WS and WA for 28 days and various parameters like body weight, organ coefficient, cytotoxicity, nitric oxide (NO), total serum protein, phagocytosis, and the gene expression levels of TLR6 and ARG genes were determined. In vivo study showed that, dose-dependent reduction in phagocytosis, an increase in the levels of NO production along with up-regulation of TLR6, arginase gene was significant (P < 0.05) when ZnO NPs were given. However toxicity of ZnO NP was reduced in presence of WS and WA with decreased TLR6 over expression and restoration of phagocytic activities. Our results provided a valuable insight into the underlying mechanism for the protective effects of WS. Mechanism of toxicity induced by Zinc oxide nanoparticles ZnO NPs and immunomodulatory protective effects of Withania somnifera extract (WS) and Withaferin A (WA), in Balb/c mice modal of peritoneal macrophages. Red arrows: effect of ZnO NPs independently leads to ROS production which attenuated the phagocytosis of yeast by macrophages through, up-regulation of TLR6 and down-regulation of arginase gene expression. Green arrows: co-treatment, Impact of Withania somnifera extract with zinc oxide nanoparticles (WS + ZnO NPs), Withaferin A along with zinc oxide nanoparticles (WA + ZnO NPs)-enhance phagocytic activity by counteracting mechanism of ZnO NPs toxicity. Black arrows: increasing or decreasing effects. Per oral (P.O).
TL;DR: Whereas Wi-A binds to vimentin and heterogeneous nuclear ribonucleoprotein K (hnRNP-K) with high efficacy and downregulates its effector proteins, MMPs and VEGF, involved in cancer cell metastasis, 3βmWi-A was ineffective.
Abstract: Withaferin-A is a withanolide, predominantly present in Ashwagandha (Withania somnifera). It has been shown to possess anticancer activity in a variety of human cancer cells in vitro and in vivo. Molecular mechanism of such cytotoxicity has not yet been completely understood. Withaferin-A and Withanone were earlier shown to activate p53 tumor suppressor and oxidative stress pathways in cancer cells. 2,3-dihydro-3β-methoxy analogue of Withaferin-A (3βmWi-A) was shown to lack cytotoxicity and well tolerated at higher concentrations. It, on the other hand, protected normal cells against oxidative, chemical and UV stresses through induction of anti-stress and pro-survival signaling. We, in the present study, investigated the effect of Wi-A and 3βmWi-A on cell migration and metastasis signaling. Whereas Wi-A binds to vimentin and heterogeneous nuclear ribonucleoprotein K (hnRNP-K) with high efficacy and downregulates its effector proteins, MMPs and VEGF, involved in cancer cell metastasis, 3βmWi-A was ineffective. Consistently, Wi-A, and not 3βmWi-A, caused reduction in cytoskeleton proteins (Vimentin, N-Cadherin) and active protease (u-PA) that are essential for three key steps of cancer cell metastasis (EMT, increase in cell migration and invasion).
TL;DR: In this article, the authors compared heat reflux (CONV), microwave assisted (MAE), SOX (SOX) and ultrasound assisted (UAE) extraction methods, using ethanol, water and their mixtures, for the recovery of bioactive compounds from Tribulus terrestris, Panax ginseng, Gingko biloba, Lepidium meyenii, Turnera diffusa and Withania somnifera.
TL;DR: Three fungal endophytes are reported from Withania somnifera, which could enhance withanolides content in leaf and root and induce a host resistant related gene, NPR1, resulting in 2, 4 and 16 fold expression levels in 2aWF, 10aWF and 5aWF endophyte treatments respectively, compared to control plants.
Abstract: Endophytes have been reported from all plant species from different parts of tissue including root, stem and leaves. Here we report, three fungal endophytes, Aspergillus terreus strain 2aWF (2aWF), Penicillium oxalicum strain 5aWF (5aWF), and Sarocladium kiliense strain 10aWF (10aWF) from Withania somnifera, which could enhance withanolides content in leaf and root. Upon treatment with the above endophytes to 4 weeks old plants in field conditions, W. somnifera elicited withanolide A content (97 to 100%) in leaves without considerable changes in withaferin A content. Furthermore, withanolide A content in roots of 5aWF and 10aWF endophyte treated W. somnifera plants increased up to 52% and 65% respectively. Incidentally, expression profile of withanolide and sterol biosynthetic pathway genes HMGR, DXR, FPPS, SQS, SQE, CAS, SMT1, STE1 and CYP710A1 were significantly upregulated in 2aWF, 5aWF and 10aWF fungal endophyte treated plants. Besides, modulation of withanolide biosynthetic pathway genes, fungal endophytes also induce a host resistant related gene, NPR1 resulting in 2, 4 and 16 fold expression levels in 2aWF, 10aWF and 5aWF endophyte treatments respectively, compared to control plants. Overall, our results illustrate that application of native-fungal endophytes 2aWF (96.60%), 5aWF (95%) and 10aWF (147%) enhances plant biomass in addition to withanolide content.
TL;DR: The study concludes that inclusion of 1.0% Withania somnifera (Ashwagandha) root extract and dietary l‐ascorbic acid (vitamin C) combination in diet have a stimulatory effect on immune response and reduces the effect of multiple stresses in L. rohita fingerlings.
TL;DR: The protective effects of herbal feed additives Silybum marianum, Withania somnifera and Centella asiatica against the toxic effects of ochratoxin A (OTA) were studied in broiler chicks aged fro...
Abstract: The protective effects of herbal feed additives Silybum marianum, Withania somnifera and Centella asiatica against the toxic effects of ochratoxin A (OTA) were studied in 70 broiler chicks aged fro...
TL;DR: The most active compound, docosanyl ferulate, was able to enhance the GABAA receptor inhibitory postsynaptic currents with an IC50 value of 7.9 μM, which cast fresh light on the biological activities of the secondary metabolites of W. somnifera roots.
Abstract: Nine compounds, including two undescribed withanolides, withasomniferolides A and B (1 and 2), three known withanolides (3-5), a ferulic acid dimeric ester (6), and an inseparable mixture of three long alkyl chain ferulic acid esters (7-9), were isolated from a GABAA receptor positive activator methanol extract of the roots of Withania somnifera. The structures of the isolated compounds were elucidated based on NMR, MS, and ECD data analysis. In order to bioassay the single ferulic acid derivatives, compounds 6-9 were also synthesized. The most active compound, docosanyl ferulate (9), was able to enhance the GABAA receptor inhibitory postsynaptic currents with an IC50 value of 7.9 μM. These results, by showing an ability to modulate the GABAA receptor function, cast fresh light on the biological activities of the secondary metabolites of W. somnifera roots.
TL;DR: The observed role of CR-777 seemed to involve the PI3K/mTOR pathway and could be considered as a protective agent against a large panel of neuronal stressors and was engaged in further therapeutic development steps.
Abstract: The bioconversion of Withania somnifera extract by the fungus Beauveria bassiana leads to cysteine and glutathione derivatives of withaferin A at the C-6 position. The compounds were purified and fully characterized by 1D-NMR, 2D-NMR, and HRMS analysis. The glutathione derivative CR-777 was evaluated as a neuroprotective agent from damage caused by different neurotoxins mimicking molecular symptoms in Parkinson´s disease (PD), including 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine (6-OHDA), and α-synuclein (α-Syn). CR-777, at nanomolar concentrations, protected dopaminergic and cortical neurons. In 6-OHDA-treated neurons, CR-777 increased cell survival and neurite network and decreased the expression of α-Syn. Using specific inhibitors of cell toxicity signaling pathways and specific staining experiments, the observed role of CR-777 seemed to involve the PI3K/mTOR pathway. CR-777 could be considered as a protective agent against a large panel of neuronal stressors and was engaged in further therapeutic development steps.