scispace - formally typeset
Search or ask a question

Showing papers on "Withania somnifera published in 2018"


Journal ArticleDOI
TL;DR: It is reported for the first time that Withaferin A (WA) can effectively combat MLD-STZ induced T1DM via modulation of Nrf2/NFκB signaling and holds substantial potential for therapy of T1 DM.

55 citations


Journal ArticleDOI
TL;DR: Novel insights are provided into the underlying mechanisms behind the tripartite interaction of endophyte-A.
Abstract: Endophytes have been explored and found to perform an important role in plant health. However, their effects on the host physiological function and disease management remain elusive. The present study aimed to assess the potential effects of endophytes, singly as well as in combination, in Withania somnifera (L.) Dunal, on various physiological parameters and systemic defense mechanisms against Alternaria alternata Seeds primed with the endophytic bacteria Bacillus amyloliquefaciens and Pseudomonas fluorescens individually and in combination demonstrated an enhanced vigor index and germination rate. Interestingly, plants treated with the two-microbe combination showed the lowest plant mortality rate (28%) under A. alternata stress. Physiological profiling of treated plants showed improved photosynthesis, respiration, transpiration, and stomatal conductance under pathogenic stress. Additionally, these endophytes not only augmented defense enzymes and antioxidant activity in treated plants but also enhanced the expression of salicylic acid- and jasmonic acid-responsive genes in the stressed plants. Reductions in reactive oxygen species (ROS) and reactive nitrogen species (RNS) along with enhanced callose deposition in host plant leaves corroborated well with the above findings. Altogether, the study provides novel insights into the underlying mechanisms behind the tripartite interaction of endophyte-A. alternata-W. somnifera and underscores their ability to boost plant health under pathogen stress.IMPORTANCEW. somnifera is well known for producing several medicinally important secondary metabolites. These secondary metabolites are required by various pharmaceutical sectors to produce life-saving drugs. However, the cultivation of W. somnifera faces severe challenge from leaf spot disease caused by A. alternata To keep pace with the rising demand for this plant and considering its capacity for cultivation under field conditions, the present study was undertaken to develop approaches to enhance production of W. somnifera through intervention using endophytes. Application of bacterial endophytes not only suppresses the pathogenicity of A. alternata but also mitigates excessive ROS/RNS generation via enhanced physiological processes and antioxidant machinery. Expression profiling of plant defense-related genes further validates the efficacy of bacterial endophytes against leaf spot disease.

53 citations


Journal ArticleDOI
TL;DR: In this article, the role of endophytes in modulating the synthesis and site of withanolide production was investigated in W. somnifera plants and their promising role in in planta withanolides biosynthesis was established in both in-vivo grown as well in in-in-vitro raised composite W. soma plants.
Abstract: Tissue specific biosynthesis of secondary metabolites is a distinguished feature of medicinal plants. Withania somnifera, source of pharmaceutically important withanolides biosynthesizes withaferin-A in leaves and withanolide-A in roots. To increase the in planta withanolides production, a sustainable approach needs to be explored. Here, we isolated endophytes from different parts of W. somnifera plants and their promising role in in planta withanolide biosynthesis was established in both in-vivo grown as well in in-vitro raised composite W. somnifera plants. Overall, the fungal endophytes improved photosynthesis, plant growth and biomass, and the root-associated bacterial endophytes enhanced the withanolide content in both in-vivo and in-vitro grown plants by modulating the expression of withanolide biosynthesis genes in leaves and roots. Surprisingly, a few indole-3-acetic acid (IAA)-producing and nitrogen-fixing root-associated endophytes could induce the biosynthesis of withaferin-A in roots by inducing in planta IAA-production and upregulating the expression of withanolide biosynthesis genes especially MEP-pathway genes (DXS and DXR) in roots as well. Results indicate the role of endophytes in modulating the synthesis and site of withanolides production and the selected endophytes can be used for enhancing the in planta withanolide production and enriching roots with pharmaceutically important withaferin-A which is generally absent in roots.

44 citations


Journal ArticleDOI
TL;DR: WS was found to enhance spermatogenesis and sperm related indices in male and sexual behaviors in female and further studies should focus on the extract preparation method and also dosage used in their study protocols.
Abstract: Introduction. Withania somnifera (WS) also known as ashwagandha is a well-known medicinal plant used in traditional medicine in many countries for infertility treatment. The present study was aimed at systemically reviewing therapeutic effects of WS on the reproductive system. Methods. This systematic review study was designed in 2016. Required data were obtained from PubMed, Scopus, Google Scholar, Cochrane Library, Science Direct, Web of Knowledge, Web of Science, and manual search of articles, grey literature, reference checking, and expert contact. Results. WS was found to improve reproductive system function by many ways. WS extract decreased infertility among male subjects, due to the enhancement in semen quality which is proposed due to the enhanced enzymatic activity in seminal plasma and decreasing oxidative stress. Also, WS extract improved luteinizing hormone and follicular stimulating hormone balance leading to folliculogenesis and increased gonadal weight, although some animal studies had concluded that WS had reversible spermicidal and infertilizing effects in male subjects. Conclusion. WS was found to enhance spermatogenesis and sperm related indices in male and sexual behaviors in female. But, according to some available evidences for spermicidal features, further studies should focus on the extract preparation method and also dosage used in their study protocols.

40 citations


Journal ArticleDOI
TL;DR: The results suggest that withanolide-A may serve as potential neuroprotective agent against glutamate-induced excitotoxicity in retinoic acid differentiated Neuro2a neuroblastoma cells.
Abstract: Glutamate-induced excitotoxicity is one of the major underlying mechanisms for neurodegenerative diseases. Efforts are being made to treat such conditions with an array of natural compounds that can modulate the release of glutamate or the underlying mechanisms associated with it. Withania somnifera extract has potent pharmacologic activity similar to that of Korean Ginseng tea and is used to treat several neuronal disorders. However, to date, little efforts have been made to evaluate individual constituents of this plant for neurodegenerative disorders. Present study was carried out to investigate withanolide-A, one of the active constituents of Withania somnifera against glutamate-induced excitotoxicity in retinoic acid differentiated Neuro2a neuroblastoma cells. The results indicated that glutamate treatment for 2 h induced death in cells that was significantly attenuated by pre-treatment with MK-801 (specific NMDA receptor antagonist) and different concentrations of withanolide-A. Withanolide-A abated the glutamate-induced influx of intracellular calcium and excessive ROS production significantly. Further on, glutamate treatment resulted in increased levels of pro-apoptotic and decreased levels of anti-apoptotic proteins, and these protein levels were normalized by various doses of withanolide-A. All of these protective effects were partly due to inhibition of MAPK family proteins and activation of PI3K/Akt signaling. Thus, our results suggest that withanolide-A may serve as potential neuroprotective agent.

37 citations


Journal ArticleDOI
TL;DR: Using phylogenetic, metabolomic, and gene expression analysis in combination with heterologous expression and virus-induced gene silencing, it is shown that 24ISO catalyzes the conversion of 24-methylenecholesterol to 24-methyldesmosterol, and proposed that this catalytic step is the committing step in withanolide biosynthesis, opening up elucidation of the whole pathway.
Abstract: A large part of chemodiversity of plant triterpenes is due to the modification of their side chains. Reduction or isomerization of double bonds in the side chains is often an important step for the diversification of triterpenes, although the enzymes involved are not fully understood. Withanolides are a large group of structurally diverse C28 steroidal lactones derived from 24-methylenecholesterol. These compounds are found in the Indian medicinal plant Withania somnifera, also known as ashwagandha, and other members of the Solanaceae. The pathway for withanolide biosynthesis is unknown, preventing sustainable production via white biotechnology and downstream pharmaceutical usages. In the present study, based on genome and transcriptome data we have identified a key enzyme in the biosynthesis of withanolides: a DWF1 paralog encoding a sterol Δ24-isomerase (24ISO). 24ISO originated from DWF1 after two subsequent duplication events in Solanoideae plants. Withanolides and 24ISO appear only in the medicinal plants in the Solanoideae, not in crop plants such as potato and tomato, indicating negative selection during domestication. 24ISO is a unique isomerase enzyme evolved from a reductase and as such has maintained the FAD-binding oxidoreductase structure and requirement for NADPH. Using phylogenetic, metabolomic, and gene expression analysis in combination with heterologous expression and virus-induced gene silencing, we showed that 24ISO catalyzes the conversion of 24-methylenecholesterol to 24-methyldesmosterol. We propose that this catalytic step is the committing step in withanolide biosynthesis, opening up elucidation of the whole pathway and future larger-scale sustainable production of withanolides and related compounds with pharmacological properties.

36 citations


Journal ArticleDOI
TL;DR: Results show that administration of WS extracts by gavage to mice expressing G93A mutant form of superoxide dismutase resulted in increased longevity, improved motor performance and increased number of motor neurons in lumbar spinal cord, suggesting that WS extracts might constitute promising therapeutics for treatment of ALS with involvement of misfolded SOD1.

34 citations


Journal ArticleDOI
TL;DR: Ashwagandha could be a powerful antioxidant and a promising anticancer agent against HCC.
Abstract: ObjectiveTo evaluate the antioxidant and apoptotic inductive effects of Withania somnifera (Ashwagandha) leaf extract against a hepatocellular carcinoma cell line.MethodsAfter treating HepG2cells w...

32 citations


Journal ArticleDOI
TL;DR: The study shows that this novel steroidal compound has potent anti‐inflammatory property and can be good remedies against many diseases if incorporated in routine diet as dietary supplement.
Abstract: Acute pancreatitis is an inflammatory disorder of the pancreas that may precipitate due to various reasons such as chronic alcoholism, gall stone obstruction, and life style. Current treatment options offer limited efficacy, as they provide only symptomatic relief. This study is an attempt to study the effects of Withaferin A (WFA) against Cerulein-induced acute pancreatitis in mice. Animals were pretreated with WFA via intraperitoneal route, for 7 days. Plasma amylase and lipase, tissue malondialdehyde (MDA), and glutathione were evaluated for all groups. Western blot analysis; haematoxylin and eosin staining of the liver, lung, and pancreas; immunohistochemistry for nitrotyrosine; and myeloperoxidase activity were performed. Haematoxylin and eosin stained sections significantly revealed the altered architecture and thereby damage in the pancreas, lungs, and liver that has been low in treatment groups. Increased myeloperoxidase and nitrotyrosine have also been reduced upon treatment with WFA. Increased levels of MDA, NO, and expression of myeloperoxidase and nitrotyrosine in the parameters estimated add evidence to the role of oxidative stress and inflammation in acute pancreatitis. WFA evidently altered these conditions upon pretreatment. Our study shows that this novel steroidal compound has potent anti-inflammatory property. Natural compounds can therefore be good remedies against many diseases if incorporated in routine diet as dietary supplement.

30 citations


Journal ArticleDOI
TL;DR: A 500 mg dose of an aqueous extract of Ashwagandha improves upper and lower-body strength, supports a favorable distribution of body mass, and was well tolerated clinically in recreationally active men over a 12-week resistance training and supplementation period.
Abstract: Withania somnifera (Ashwagandha) is an Ayurvedic herb categorized as having “rasayana” (rejuvenator), longevity, and revitalizing properties. Sensoril® is a standardized aqueous extract of the roots and leaves of Withania somnifera. Purpose: To examine the impact of Sensoril® supplementation on strength training adaptations. Methods: Recreationally active men (26.5 ± 6.4 years, 181 ± 6.8 cm, 86.9 ± 12.5 kg, 24.5 ± 6.6% fat) were randomized in a double-blind fashion to placebo (PLA, n = 19) or 500 mg/d Sensoril® (S500, n = 19). Body composition (DEXA), muscular strength, power, and endurance, 7.5 km cycling time trial, and clinical blood chemistries were measured at baseline and after 12 weeks of supplementation and training. Subjects were required to maintain their normal dietary habits and to follow a specific, progressive overload resistance-training program (4-day/week, upper body/lower body split). 2 × 2 mixed factorial ANOVA was used for analysis and statistical significance was set a priori at p ≤ 0.05. Results: Gains in 1-RM squat (S500: +19.1 ± 13.0 kg vs. PLA +10.0 ± 6.2 kg, p = 0.009) and bench press (S500: +12.8 ± 8.2 kg vs. PLA: +8.0 ± 6.0 kg, p = 0.048) were significantly greater in S500. Changes in DEXA-derived android/gynoid ratio (S500: +0.0 ± 0.14 vs. PLA: +0.09 ± 0.1, p = 0.03) also favored S500. No other between-group differences were found for body composition, visual analog scales for recovery and affect, or systemic hemodynamics, however, only the S500 group experienced statistically significant improvements in average squat power, peak bench press power, 7.5 km time trial performance, and perceived recovery scores. Clinical chemistry analysis indicated a slight polycythemia effect in PLA, with no other statistical or clinically relevant changes being noted. Conclusions: A 500 mg dose of an aqueous extract of Ashwagandha improves upper and lower-body strength, supports a favorable distribution of body mass, and was well tolerated clinically in recreationally active men over a 12-week resistance training and supplementation period.

29 citations


Journal ArticleDOI
TL;DR: An endophytic fungus is identified from leaves of Withania somnifera which produces withanolides in the medium and the structure of withanolide was confirmed by 1H NMR, LC-MS analyses and quantified by HPLC analysis.

Journal ArticleDOI
TL;DR: It was found that WS-AgNPs inhibited growth of pathogenic bacteria even at 16 µg/ml, and at sub-minimum inhibitory concentration concentration, there was approximately 50% inhibition in biofilm formation which was further validated by light and electron microscopy.
Abstract: Multi-drug resistance in pathogenic bacteria has created immense clinical problem globally. To address these, there is need to develop new therapeutic strategies to combat bacterial infections. Silver nanoparticles (AgNPs) might prove to be next generation nano-antibiotics. However, improved efficacy and broad-spectrum activity is still needed to be evaluated and understood. The authors have synthesised AgNPs from Withania somnifera (WS) by green process and characterised. The effect of WS-AgNPs on growth kinetics, biofilm inhibition as well as eradication of preformed biofilms on both gram-positive and gram-negative pathogenic bacteria was evaluated. The authors have demonstrated the inhibitory effect on bacterial respiration and disruption of membrane permeability and integrity. It was found that WS-AgNPs inhibited growth of pathogenic bacteria even at 16 µg/ml. At sub-minimum inhibitory concentration concentration, there was approximately 50% inhibition in biofilm formation which was further validated by light and electron microscopy. WS-AgNPs also eradicated the performed biofilms by varying levels at elevated concentration. The bacterial respiration was also significantly inhibited. Interaction of WS-AgNPs with test pathogen caused the disruption of cell membrane leading to leakage of cellular content. The production of intracellular reactive oxygen species reveals that WS-AgNPs exerted oxidative stress inside bacterial cell causing microbial growth inhibition and disrupting cellular functions.

Journal ArticleDOI
TL;DR: The present review provides a comprehensive report on research activities conducted in the area of tissue culture and secondary metabolite production in W. somnifera during the past years and discusses the unexplored areas which might be taken into consideration for future research.
Abstract: Withania somnifera (L.) Dunal (family: Solanaceae), commonly known as "Indian Ginseng", is a medicinally and industrially important plant of the Indian subcontinent and other warmer parts of the world. The plant has multi-use medicinal potential and has been listed among 36 important cultivated medicinal plants of India that are in high demand for trade due to its pharmaceutical uses. The medicinal importance of this plant is mainly due to the presence of different types of steroidal lactones- withanolides in the roots and leaves. Owing to low seed viability and poor germination, the conventional propagation of W. somnifera falls short to cater its commercial demands particularly for secondary metabolite production. Therefore, there is a great need to develop different biotechnological approaches through tissue and organ culture for seasonal independent production of plants in large scale which will provide sufficient raw materials of uniform quality for pharmaceutical purposes. During past years, a number of in vitro plant regeneration protocols via organogenesis and somatic embryogenesis and in vitro conservation through synthetic seed based encapsulation technology have been developed for W. somnifera. Several attempts have also been made to standardize the protocol of secondary metabolite production via tissue/organ cultures, cell suspension cultures, and Agrobacterium rhizogenes-mediated transformed hairy root cultures. Employment of plant tissue culture based techniques would provide means for rapid propagation and conservation of this plant species and also provide scope for enhanced production of different bioactive secondary metabolites. The present review provides a comprehensive report on research activities conducted in the area of tissue culture and secondary metabolite production in W. somnifera during the past years. It also discusses the unexplored areas which might be taken into consideration for future research so that the medicinal properties and the secondary metabolites produced by this plant can be exploited further for the benefit of human health in a sustainable way.

Journal ArticleDOI
TL;DR: A putative mechanistic concept considering growth responses, physiological behaviour, and metabolite content and gene expression aspects is presented and drought induced metabolic and physiological responses as well as drastic decrease in CO2 uptake due to stomatal limitations are presented.

Journal ArticleDOI
TL;DR: This study provides first ever preclinical evidence and scientific validation that ASH-WEX exhibits the anti-neuroinflammatory potential against systemic LPS-induced neuroinflammation and ameliorates associated behavioral abnormalities.
Abstract: Reactive gliosis, microgliosis, and subsequent secretion of various inflammatory mediators like cytokines, proteases, reactive oxygen, and nitrogen species are the suggested key players associated with systemic inflammation-driven neuroinflammation and cognitive impairments in various neurological disorders. Conventionally, non-steroidal anti-inflammatory drugs are prescribed to suppress inflammation but due to their adverse effects, their usage is not well accepted. Natural products are emerging better therapeutic agents due to their affordability and inherent pleiotropic biological activities. In Ayurveda, Ashwagandha (Withania somnifera) is well known for its immunomodulatory properties. The current study is an extension of our previous report on in vitro model system and was aimed to investigate anti-neuroinflammatory potential of water extract from the Ashwagandha leaves (ASH-WEX) against systemic LPS-induced neuroinflammation and associated behavioral impairments using in vivo rat model system. Oral feeding of ASH-WEX for 8 weeks significantly ameliorated the anxiety-like behavior as evident from Elevated plus maze test. Suppression of reactive gliosis, inflammatory cytokines production like TNF-α, IL-1β, IL-6, and expression of nitro-oxidative stress enzymes like iNOS, COX2, NOX2 etc were observed in ASH-WEX-treated animals. NFκB, P38, and JNK MAPKs pathways analysis showed their involvement in inflammation suppression which was further confirmed by inhibitor studies. The current study provides first ever preclinical evidence and scientific validation that ASH-WEX exhibits the anti-neuroinflammatory potential against systemic LPS-induced neuroinflammation and ameliorates associated behavioral abnormalities. Aqueous extract from Ashwagandha leaves and its active phytochemicals may prove to be promising candidates to prevent neuroinflammation associated with various neuropathologies.

Journal ArticleDOI
TL;DR: W. somnifera, a traditional medicine remedy, improves sperms parameters in idiopathic male infertility without causing adverse effects and can be considered to be an alternative to pentoxifylline in this regard.
Abstract: In this triple-blind randomised clinical trial, we compared the effects of Withania somnifera and pentoxifylline on the sperm parameters in idiopathic male infertility. One hundred infertile male patients were randomly allocated into either W. somnifera or pentoxifylline groups. Patients in the herbal group received six capsules containing 5 g/daily of W. somnifera root, and subjects in the pentoxifylline group received six capsules containing 800 mg/daily of pentoxifylline and placebo for 90 days. Sperm parameters were analysed at the beginning and end of the study. W. somnifera increased mean sperm count (12.5%) and progressive motility (21.42%) and improved sperm morphology (25.56%) compared to the baseline (p = .04, p = .001 and p = .000 respectively). Moreover, pentoxifylline increased mean semen volume (16.46%), progressive motility (25.97%) and improved sperm morphology (13.28%) versus the baseline (p = .02, p = .003 and p = .01 respectively). Intergroup comparison showed no significant differences between the two groups regarding semen volume (p = .11), sperm count (p = .09), morphology (p = .12) and progressive motility (p = .77) after treatment. No major complication was reported in either of the two groups. W. somnifera, a traditional medicine remedy, improves sperms parameters in idiopathic male infertility without causing adverse effects. Therefore, this medication can be considered to be an alternative to pentoxifylline in this regard.

Journal ArticleDOI
TL;DR: The finding that the two most efficient bacterial endophytes namely Bacillus amyloliquefaciens and Pseudomonas fluorescens individually as well as in combination were able to modulate withanolide biosynthetic pathway and tolerance against Alternaria alternata in Withania somnifera highlights novel insights into the underlying mechanisms in application of endophyte.

Journal ArticleDOI
TL;DR: Results show protective effect of WS pre-supplementation in ischemic stroke and are suggestive of its potential application in stroke management.
Abstract: Stroke is an increasingly prevalent clinical condition and second leading cause of death globally. The present study evaluated the therapeutic potential of Indian Ginseng, also known as Withania somnifera (WS), supplementation on middle cerebral artery occlusion (MCAO) induced mitochondrial dysfunctions in experimental model of ischemic stroke. Stroke was induced in animals by occluding the middle cerebral artery, followed by reperfusion injury. Ischemia reperfusion injury resulted in increased oxidative stress indicated by increased reactive oxygen species and protein carbonyl levels; compromised antioxidant system; in terms of reduced superoxide dismutase and catalase activity, along with reduction in GSH levels and the redox ratio, impaired mitochondrial functions and enhanced expression of apoptosis markers. Ischemia reperfusion injury induced mitochondrial dysfunctions in terms of (i) reduced activity of the mitochondrial respiratory chain enzymes, (ii) reduced histochemical staining of complex-II and IV, (iii) reduced in-gel activity of mitochondrial complex-I to V, (iv) mitochondrial structural changes in terms of increased mitochondrial swelling, reduced mitochondrial membrane potential and ultrastructural changes. Additionally, an increase in the activity of caspase-3 and caspase-9 was also observed, along with altered expression of apoptotic proteins Bcl-2 and Bax in MCAO animals. MCAO animals also showed significant impairment in cognitive functions assessed using Y maze test. WS pre-supplementation, on the other hand ameliorated MCAO induced oxidative stress, mitochondrial dysfunctions, apoptosis and cognitive impairments. The results show protective effect of WS pre-supplementation in ischemic stroke and are suggestive of its potential application in stroke management.

Journal ArticleDOI
TL;DR: Evaluated phytochemicals have neuroprotective potential as an inherently useful oral drug to combat ischemic and hemorrhagic stroke mediated by gelatinases and suggest higher affinity for MMP-2 compared with gelatinases inhibitors.
Abstract: A stroke or cerebrovascular accident is a serious, life-threatening medical condition that occurs when the blood supply to part of the brain is severely reduced or cut off, depriving brain tissue of oxygen and nutrients. Studies suggested that level of gelatinases (MMP-2 and MMP-9) usually increases in the brain after stroke. The elevated activity of gelatinases plays the deleterious role in ischemic stroke, hemorrhagic stroke and perinatal hypoxic-ischemic brain injury. Therefore, matrix metalloproteinase (MMP)-2 and MMP-9 inhibition have therapeutic importance in stroke condition. Present in silico study investigates whether Withania somnifera (WS) phytochemicals inhibit the MMP-2 and MMP-9 by binding to the catalytic domain, as similar to their inhibitor or not. For that, we performed molecular docking study to evaluate the gelatinases-inhibitory potential of 36 WS phytochemicals, which compared with gelatinases inhibitors viz. hydroxamic acid, quercetin, doxycycline, minocycline and reverse hydroxamate. The results suggest that 28 out of 36 WS phytochemicals show higher affinity for MMP-2 owing to bind with active site residues of S1'-pocket with lower binding energy and smaller inhibition constant (Ki) than considered inhibitors. As well as, withanolide G and withafastuosin E show higher affinity for MMP-9 than reverse hydroxamate inhibitor. These phytochemicals have neuroprotective potential as an inherently useful oral drug to combat ischemic and hemorrhagic stroke mediated by gelatinases.

Journal Article
TL;DR: In this article, the effect of CuO nanoparticles on polyphenols content in treated plants at different dates of sampling was investigated and the results showed that the elicitation effect of the nanoparticles in Withania somnifera L. L. 20 days after treatment was significant.
Abstract: In the present investigation CuO nanoparticles significantly enhanced the polyphenols content in treated plants at different dates of sampling. Highest total phenol content i.e., 27.215±0.73 and 26.455±0.365 mg gallic acid equivalents/g extract, was observed 20 days after treatment in shoots and roots of treated plants, respectively. No significant difference (p≤0.05) in flavonoid content within shoots of treated plants was observed 15 and 20 DAT, respectively. Highest flavonoid content i.e., 23.076±5.128 mg quercetin equivalents/g extract was observed in roots of treated plants 20 days after treatment. Significantly higher tannin content was also observed in roots of treated plants20 DAT. Higher total antioxidant activity i.e., 55.797±1.924 and 56.811±3.012mg ascorbic acid equivalents/g extract was observed in shoots and roots of treated plants, respectively 20 days after treatment. Higher DPPH radical scavenging activity as observed by lower IC50 values i.e., 336.234±5.187 and 473.88±8.834 µg/ml in shoots and roots of treated plants, respectively was observed 20 days after treatment. Total antioxidant activity in shoots showed a significant (p≤0.05) positive correlation with phenol and tannin content within the shoots i.e., 0.618 and 0.693, respectively. Total antioxidant activity in roots also showed significant positive correlation with total phenol, flavonoid and tannin content within roots i.e., 0.416, 0.683 and 0.891, respectively. DPPH radical scavenging activity within shoots (-0.888) and roots (-0.851) showed a significant negative correlation with total phenol and flavonoid content in shoots and roots, respectively. Thus the findings of the present investigation clearly shows, the elicitation effect of CuO nanoparticles in Withania somnifera L.

Journal ArticleDOI
TL;DR: Specific miRNAs and their corresponding target genes for corresponding root and leaf tissues are reported here, and the target genes have also been analyzed for their role in withanolide metabolism.
Abstract: Withania somnifera, popularly known as Indian ginseng, is one of the most important medicinal plants. The plant is well studied in terms of its pharmaceutical activities and genes involved in biosynthetic pathways. However, not much is known about the regulatory mechanism of genes responsible for the production of secondary metabolites. The idea was to identify miRNA transcriptome responsible for the regulation of withanolide biosynthesis, specifically of root and leaf tissues individually. The transcriptome data of in vitro culture of root and leaf tissues of the plant was considered for miRNA identification. A total of 24 and 39 miRNA families were identified in root and leaf tissues, respectively. Out of these, 15 and 27 miRNA families have shown their involvement in different biological functions in root and leaf tissues, respectively. We report here, specific miRNAs and their corresponding target genes for corresponding root and leaf tissues. The target genes have also been analyzed for their role in withanolide metabolism. Endogenous root-miR5140, root-miR159, leaf-miR477, and leaf-miR530 were reported for regulation of withanolide biosynthesis.

Journal ArticleDOI
TL;DR: It is concluded that basal rot of onion can be controlled by combined application of W. somnifera dry leaf material and biological control agent T. harzianum.
Abstract: Onion is attacked by destructive soil-borne fungal plant pathogen Fusarium oxysporum f. sp. cepae, resulting in basal rot disease. In the present study, three Trichoderma species (T. pseudokoningii, T. harzianum and T. reesei) and leaves of solanaceous weed Withania somnifera were used for management of this disease. The in vitro interaction study revealed T. harzianum as the most effective biocontrol agent against the pathogen. In a pot trial, dried leaf material of W. somnifera (1%, 2% and 3% w/w) and inoculum of T. harzianum were mixed in the pot soil previously inoculated with the pathogen. The highest incidence of the disease (87%) was found in positive control (pathogen inoculation without any amendment). Different rates of dry leaf material reduced the incidence of the disease to 41-66%. T. harzianum in combination with leaf material reduced the incidence of the disease to 20-53%. In a laboratory bioassay, the dry leaf extract of W. somnifera was prepared in methanol and partitioned with n-hexane, chloroform, ethyl acetate and n-butanol. The highest concentration (200 mg mL-1) of all except for the n-butanol fraction significantly decreased fungal biomass over control. This study concludes that basal rot of onion can be controlled by combined application of W. somnifera dry leaf material and biological control agent T. harzianum.

Journal ArticleDOI
16 Apr 2018-PLOS ONE
TL;DR: A simple and inexpensive method for improving the yield and pharmaceutical components of Ashwagandha leaves and showed anticancer activities in cell culture assays.
Abstract: Withania somnifera (Ashwagandha) has recently been studied extensively for its health-supplementing and therapeutic activities against a variety of ailments. Several independent studies have experimentally demonstrated pharmaceutical potential of its active Withanolides, Withaferin A (Wi-A), Withanone (Wi-N) and Withanolide A (Wil-A). However, to promote its use in herbal industry, an environmentally sustainable cultivation and high yield are warranted. In modern agriculture strategies, there has been indiscriminate use of chemical fertilizers to boost the crop-yield, however the practice largely ignored its adverse effect on the quality of soil and the environment. In view of these, we attempted to recruit Vermicompost (Vcom, 20-100%) as an organic fertilizer of choice during the sowing and growing phases of Ashwagandha plants. We report that (i) pre-soaking of seeds for 12 h in Vermicompost leachate (Vcom-L) and Vermicompost tea (Vcom-T) led to higher germination, (ii) binary combination of pre-soaking of seeds and cultivation in Vcom (up to 80%) resulted in further improvement both in germination and seedling growth, (iii) cultivated plants in the presence of Vcom+Vcom-L showed higher leaf and root mass, earlier onset of flowering and fruiting and (iv) leaves from the Vcom+Vcom-L cultivated plants showed higher level of active Withanolides, Withanone (Wi-N), Withanolide A (Wil-A) and Withaferin A (Wi-A) and showed anticancer activities in cell culture assays. Taken together, we report a simple and inexpensive method for improving the yield and pharmaceutical components of Ashwagandha leaves.

Journal ArticleDOI
25 May 2018
TL;DR: It was summarized that photosynthesis, stomatal conductance, water use efficiency, leaf, and soil carbon and biomass increased under ECs rendering the physiological adaptation to the plant.
Abstract: Winter cherry or Ashwagandha (Withania somnifera) is an important medicinal plant used in traditional and herbal medicine system. Yet, there is no information available on response of this plant to changing climatic conditions particularly elevated atmospheric CO2 concentrations. Therefore, we conducted an experiment to examine the effect of elevated CO2 concentrations (ECs) on Withania somnifera. The variations in traits of physiological adaptation, net primary productivity, carbon partitioning, morphology, and biomass in response to elevated CO2 concentrations (ambient, 600 and 800 µmol mol−1) during one growth cycle were investigated within the open top chamber (OTC) facility in the foothill of the Himalayas, Dehardun, India. ECs significantly increased photosynthetic rate, transpiration rate, stomatal conductance, water use efficiency, soil respiration, net primary productivity and the carbon content of plant tissues (leaf, stem, and root), and soil carbon. Furthermore, ECs significantly enhanced biomass production (root and shoot), although declined night leaf respiration. Overall, it was summarized that photosynthesis, stomatal conductance, water use efficiency, leaf, and soil carbon and biomass increased under ECs rendering the physiological adaptation to the plant. Increased net primary productivity might facilitate mitigation effects by sequestering elevated levels of carbon dioxide. We advocate further studies to investigate the effects of ECs on the accumulation of secondary metabolites and health-promoting substances of this as well as other medicinal plants.

Journal ArticleDOI
TL;DR: The present study concluded that presence of mycorrhiza was effective on plant growth and phytochemical constituents more than non-treated plants.
Abstract: Mycorrhizal inoculation in the plant causing increase in growth and production of phytochemicals is well reported, however little information is available related to the effect of mycorrhiza on morphological and biochemical properties of the medicinal plants like Ashwagandha. The present study is an attempt on diversity analysis in Withania somnifera with an aim to ascertain the nature and extent of genetic diversity present among different accessions in presence of mycorrhiza. The major biochemical constituents of Ashwaganda roots are with nolides which are well known for its medicinal properties. Mycorrhizal associations confer benefits like better nutrition acquisition, enhanced growth, defense enhancement and improved abiotic and biotic stress tolerance in plants. The present investigation was undertaken to assess genetic diversity among five different accessions of W. somnifera using morphological and biochemical markers and the effect of mycorrrhizal inoculation on these marker. The present study concluded that presence of mycorrhiza was effective on plant growth and phytochemical constituents more than non-treated plants. Amongst five selected germplasms IC 283662, JA 134, RAS 23, MPAS 6 and MWS 205 of W. somnifera, JA 134 showed best response in pretext of the selected morphological and biochemical features in presence of mycorrhiza.

Journal ArticleDOI
TL;DR: It is shown that besides other mechanisms, the inhibition of Infectious Bursal Disease virus by Withania somnifera involves the production of nitric oxide.
Abstract: Infectious Bursal Disease is a severe viral disease of chicken responsible for serious economic losses to poultry farmers. The causative agent, Infectious Bursal Disease virus, is inhibited by nitric oxide. Root extract of the Indian ginseng, Withania somnifera, inhibits Infectious Bursal Disease virus in vitro. Also, Withania somnifera root extract is known to induce nitric oxide production in vitro. Therefore, the present study was undertaken to determine if the inhibitory activity of Withania somnifera against Infectious Bursal Disease virus was based on the production of nitric oxide. We show that besides other mechanisms, the inhibition of Infectious Bursal Disease virus by Withania somnifera involves the production of nitric oxide. Our results also highlight the paradoxical role of nitric oxide in the pathogenesis of Infectious Bursal Disease.

Journal ArticleDOI
TL;DR: It is indicated that WsMBP1 can act as a potential gene resource in future transformation programs for incorporating insect pest tolerance in susceptible plant genotypes.
Abstract: Lectins are carbohydrate-binding proteins with wide array of functions including plant defense against pathogens and insect pests. In the present study, a putative mannose-binding lectin (WsMBP1) of 1124 bp was isolated from leaves of Withania somnifera. The gene was expressed in E. coli, and the recombinant WsMBP1 with a predicted molecular weight of 31 kDa was tested for its insecticidal properties against Hyblaea puera (Lepidoptera: Hyblaeidae) and Probergrothius sanguinolens (Hemiptera: Pyrrhocoridae). Delay in growth and metamorphosis, decreased larval body mass and increased mortality was recorded in recombinant WsMBP1-fed larvae. Histological studies on the midgut of lectin-treated insects showed disrupted and diffused secretory cells surrounding the gut lumen in larvae of H. puera and P. sanguinolens, implicating its role in disruption of the digestive process and nutrient assimilation in the studied insect pests. The present study indicates that WsMBP1 can act as a potential gene resource in future transformation programs for incorporating insect pest tolerance in susceptible plant genotypes.

Journal ArticleDOI
TL;DR: The results suggest that ashwagandha extract possesses antioxidant and anti-inflammatory effects against aluminum neurotoxicity and could prevent the decline in cholinergic activity by maintaining normal acetylcholinesterase activity.
Abstract: Objective: To evaluate the neuroprotective effect of ashwagandha extract against aluminum chloride-induced neurotoxicity in rats. Methods: Rats were divided into control, aluminum-intoxicated rats treated daily with aluminum trichloride (AlCl3) (100 mg/kg, orally) for 30 d and aluminum-intoxicated animals protected by receiving daily ashwagandha extract (200 mg/kg, orally) one hour before AlCl3 administration for 30 d. Levels of lipid peroxidation, nitric oxide, reduced glutathione and tumor necrosis factor-α were measured in the cortex, hippocampus and striatum. In addition, the activities of Na+, K+, ATPase and acetylcholinesterase were determined in the three studied brain regions. Results: Aluminum increased the levels of lipid peroxidation and nitric oxide in the cortex, hippocampus and striatum and decreased the reduced glutathione level in the hippocampus and striatum. In rats protected with ashwagandha extract, non significant changes were observed in lipid peroxidation, nitric oxide and reduced glutathione. In addition, ashwagandha extracts prevented the increased activity of acetylcholinesterase and Na+, K+, ATPase induced by AlCl3 in the cortex, hippocampus and striatum. The present findings also showed that the significant increase in tumor necrosis factor-α induced by AlCl3 in the cortex and hippocampus was prevented by ashwagandha extract. Conclusions: The present results suggest that ashwagandha extract possesses antioxidant and anti-inflammatory effects against aluminum neurotoxicity. In addition, ashwagandha extract could prevent the decline in cholinergic activity by maintaining normal acetylcholinesterase activity. The later effect could recommend the use of ashwagandha as a memory enhancer.

Journal ArticleDOI
TL;DR: It is demonstrated that transcriptional regulation of selected Withania genes of the triterpenoid biosynthetic pathway critically affects withanolide biosynthesis, providing new horizons to explore this process further, in planta.
Abstract: Withanolides are a collection of naturally occurring, pharmacologically active, secondary metabolites synthesized in the medicinally important plant, Withania somnifera. These bioactive molecules are C28-steroidal lactone triterpenoids and their synthesis is proposed to take place via the mevalonate (MVA) and 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways through the sterol pathway using 24-methylene cholesterol as substrate flux. Although the phytochemical profiles as well as pharmaceutical activities of Withania extracts have been well studied, limited genomic information and difficult genetic transformation have been a major bottleneck towards understanding the participation of specific genes in withanolide biosynthesis. In this study, we used the Tobacco rattle virus (TRV)-mediated virus-induced gene silencing (VIGS) approach to study the participation of key genes from MVA, MEP and triterpenoid biosynthesis for their involvement in withanolide biosynthesis. TRV-infected W. somnifera plants displayed unique phenotypic characteristics and differential accumulation of total Chl as well as carotenoid content for each silenced gene suggesting a reduction in overall isoprenoid synthesis. Comprehensive expression analysis of putative genes of withanolide biosynthesis revealed transcriptional modulations conferring the presence of complex regulatory mechanisms leading to withanolide biosynthesis. In addition, silencing of genes exhibited modulated total and specific withanolide accumulation at different levels as compared with control plants. Comparative analysis also suggests a major role for the MVA pathway as compared with the MEP pathway in providing substrate flux for withanolide biosynthesis. These results demonstrate that transcriptional regulation of selected Withania genes of the triterpenoid biosynthetic pathway critically affects withanolide biosynthesis, providing new horizons to explore this process further, in planta.

Journal ArticleDOI
TL;DR: This study indicated that promoting an elite variety through tissue culture with consistency in the withanolide contents can be a promising approach to meet the growing demand of Ashwagandha.
Abstract: Five varieties of Ashwagandha (Withania somnifera L. (Dunal) i.e. Chetak, Pratap, Nimithli, Poshita and Jawahar-20 were analyzed for withanolide A and withaferin A. These components were evaluated from leaf, stem, root and seeds using HPLC. These components were present in all these tissues. However, their content varies from tissues to tissue and variety to variety viz (Chetak, Pratap, Nimithli, Poshita and Jawahar-20). Withaferin A and withanolide A contents were found to be highest in Poshita followed by Jawahar-20. Withaferin A and withanolide A contents were also evaluated and compared in field-grown and in-vitro grown plants of Poshita and Jawahar-20. Callus derived from Poshita root showed the highest withaferin A content however, withanolide A was found to be highest in callus derived from Jawahar-20 leaf. Thus this study indicated that promoting an elite variety through tissue culture with consistency in the withanolide contents can be a promising approach to meet the growing demand of Ashwagandha. Key-words: Withania somnifera, Withaferin A, Withanolide A, HPLC, Field grown, In-vitro grown, Ashwagandha INTRODUCTION Withania somnifera (L.) Dunal, popularly known as Ashwagandha, is a high valued medicinal plant of India. It is a priority medicinal plant which is identified by National Medicinal Plant Board of India. The roots and leaves of Ashwagandha contain various alkaloids viz withanolides [1] and withaferin A . Among withanolides, withaferin A and withanolide A have been reported to be dominant metabolite distributed among various tissues of this plant in varying concentrations . How to cite this article Singh M, Shah P, Punetha H, Agrawal S. Varietal Comparison of Withanolide