Withania Somnifera Dunal Research Articles

Ashwagandha- Withania somnifera (L.) Dunal as a multipotent neuroprotective remedy for genetically induced motor dysfunction and cellular toxicity in human neurodegenerative disease models of Drosophila

Ethnopharmacological relevanceAshwagandha-Withania somnifera (L.) Dunal, well known for its multipotent therapeutic properties has been used in Ayurveda for 3000 years. The plant with more than 50 active phytoconstituents is recognised for its anti-cancerous, anti-diabetic, anti-inflammatory, anti-microbial, and neurotherapeutic properties demonstrated in in vitro studies and chemically induced rodent models. Genetically targeted Parkinson’s, Alzheimer’s and other neurodegenerative disease models have been created in Drosophila and have been used to get mechanistic insight into the in vivo cellular events, and genetic pathways that underlie respective neurodegenerative condition. But hitherto, there aren’t enough attempts made to capitalize the genetic potential of these disease models to validate the therapeutic efficacy of different reagents used in traditional medicine, in the context of specific disease-causing genetic mutations. Aim of the studyDrugs discovered using in vitro platforms might fail in several instances of clinical trials because of the genetic heterogeneity and variability in the physiological context found among the patients. Drosophila by virtue of its genetically regulated experimental potential forms an ideal in vivo model to validate the candidate reagents discovered in in vitro screens for their efficacy under specific genetic situations. Here we have used genetically induced α-synucleinopathy and tauopathy transgenic fly models to study the efficacy of Ashwagandha treatment, assessing cellular and behavioural parameters. MethodsWe have expressed the disease-causing human gene mutations in specific cell types of Drosophila using GAL4/UAS targeted expression system to create disease models. Human α-synuclein mutant (A30P) was expressed in dopaminergic neurons using Ddc-GAL4 driver strain to induce dopaminergic neurodegeneration and assayed for motor dysfunction. Human TauE14, mutant protein was expressed in photoreceptor neurons using GMR-GAL4 driver to induce photoreceptor degeneration. Microtubular destability and mitotic arrest in the dividing photoreceptor precursor cells were studied using αPH3 antibody. Lysosomal dysregulation caused necrotic black spots were induced by TauE14 with GMR-GAL4 driver, in a white mutant background. These flies mimicking neurodegenerative conditions were supplemented with different concentrations of Ashwagandha aqueous root extract mixed with regular fly food. The treated flies were analysed for cellular and behaviour parameters. ResultsLifespan assay shows that, Ashwagandha-root extract imparts an extended lifespan in male Drosophila flies which are intrinsically less stress resistant. Motor dysfunction caused due to human α-synuclein mutant protein expressed in dopaminergic neurons is greatly brought down. Further, Ashwagandha extract treatment significantly reduces TauE14 induced microtubular destability, mitotic arrest and neuronal death in photoreceptor neurons. Our experiment with tauopathy model in white mutant background exemplify that, Ashwagandha-root extract treatment can bring down lysosomal dysregulation induced necrosis of photoreceptor neurons. ConclusionWe have carried out a multifaceted study which elucidates that Ashwagandha can serve as a comprehensive, phytotherapeutic formulation to combat neurodegeneration, targeting multiple causative genetically defective conditions.

The Ameliorative Effect of Ashwagandha- Withania somnifera (L.) Dunal on park25 Induced Neurodegeneration in Drosophila melanogaster Parkinson’s Disease Model

Ashwagandha - Withania somnifera (L.) Dunal is a perennial shrub belonging to the family Solanaceae. Ashwagandha has been used for over 3000 years in traditional Indian Ayurveda for treatment of various neurological, and stress disorders. The root of Ashwagandha (ASH) is regarded as a tonic, aphrodisiac, narcotic, diuretic, anthelmintic, astringent, thermogenic and stimulant. Ashwagandha with other herbal decoctions was recognized to treat Kampavatha (Parkinson’s Disease) since 18th century. With this wide array of ethnopharmacological relevance, Ashwagandha has been recognized as one of the prominent complementary and alternative medicine to treat many neurodegenerative diseases like Alzheimer’s (AD) and Parkinson’s disease (PD). There is a prominent increase in the cases of AD and PD all over the world and it demands the requirement of complementary and alternative herbal remedies with no/minimal side effects. Many genetic factors are responsible for the onset and progression of PD. Loss-of-function mutations in the parkin gene are a major cause of early onset of autosomal recessive juvenile parkinsonism (AR-JP). Drosophila park25 loss of function mutants exhibit significantly increased number of mitochondria-endoplasmic reticulum contacts and a significantly decreased number of dopaminergic neurons in the adult brain which is the main cause of PD condition. Several studies have demonstrated the ability of Ashwagandha in imparting neuroprotection, improved locomotory ability, memory and learning abilities. The challenge lies in scrutinizing the mechanism and the pathways involved in the neuroprotective properties of this well-known herb. Here in our study, we test the possible neuroprotective effect of Ashwagandha on park25 mutants of Drosophila using lifespan analysis and climbing disability as a disease marker. Parkinson’s mimicking flies were administered with aqueous extraction of Ashwagandha-root mixed with the fly food and subjected to negative geotaxis assay. We observed that there is a prominent increase in the climbing ability in park25 treated flies compared to its age-matched untreated flies. This is the first report showing that, aqueous extraction of Ashwagandha-root extract was able to ameliorate the disease phenotype in the park25 Drosophila Parkinson’s disease model.

Human tau E14 Mutation Induced Neurodegeneration in Drosophila melanogaster is Ameliorated by Developmental Supplement of Ashwagandha Root Extract

Withania somnifera (L.) Dunal (WS) known as Ashwagandha, has been used for centuries in Ayurvedic medicine to promote longevity and vitality. The use of herbal plant extract in treating several diseases has been documented from the very beginning in Ayurveda. The ethnopharmacological properties of this ‘‘Indian Ginseng’’ plant include adaptogenic, hypnotic, sedative, and diuretic. The root extract of WS has shown the properties of neuronal regeneration by stimulating axon and dendrite outgrowth in neurons in culture. Hence, in the recent decade Ashwagandha has been widely studied for its neuroprotective properties in many rodent models and cell lines. Here, we have used transgenic Drosophila model carrying human tauE14. The mutant protein codes for pseudophosphorylated Tau protein which is specifically expressed in photoreceptor neurons using GMR-Gal4 driver to induce photoreceptor neuronal degeneration. We treated these tauopathy mimicking flies with different concentrations of Ashwagandha to evaluate the neuroprotective/remedial effect of Ashwagandha at different stages of fly development. Our results demonstrated that Ashwagandha can rescue the neurodegeneration phenotype in Drosophila TauE14 disease model only when administered during development.

Optimization of culture conditions for in vitro propagation of medicinally important plant Withania somnifera (Ashwagandha)

Withania somnifera Dunal is an evergreen, upright, perennial herb commonly named Indian ginseng which falls in Solanaceae family. The plant is recognized worldwide for its therapeutic properties, it contains secondary metabolites of flavonoids class and many active ingredients like withanolide, withaferin etc. Effort was made to optimize the rejuvenation process for this medicinally important plant. MS media were adjusted for leaf regeneration and for callus induction of this plant. In vitro rejuvenation of leaf sprouts was accomplished from nodal segments cultivated on media complemented with BAP (1.0-3.0 mg/L) alone and in synergy with KN i.e. BAP (1.5-4.0 mg/L) + KN (1.0-2.0mg/L). The quantity of shoots per explants was recorded highest in MS media complemented with BAP (2.0 mg/L) + KN (2.0 mg/L) with 85% shooting response and average shoot length approximately 3.6 cm. was promoted by BAP (4.0 mg/L)+KN (2.0 mg/L). Different explants (leaf and nodal segments) were used to establish callus. Induction of callus was detected best in MS media complemented with 2,4- D 2.0 mg/L after 20-30 days (75%).

Molecular Mechanism behind the Safe Immunostimulatory Effect of Withania somnifera.

Withania somnifera (L.) Dunal (family Solanaceae) is a medicinal plant known for, among many pharmacological properties, an immune boosting effect. Our recent study revealed that its key immunostimulatory factor is lipopolysaccharide of plant-associated bacteria. This is peculiar, because, although LPS can elicit protective immunity, it is an extremely potent pro-inflammatory toxin (endotoxin). However, W. somnifera is not associated with such toxicity. In fact, despite the presence of LPS, it does not trigger massive inflammatory responses in macrophages. To gain insights into the safe immunostimulatory effect of W. somnifera, we conducted a mechanistic study on its major phytochemical constituent, withaferin A, which is known for anti-inflammatory activity. Endotoxin-triggered immunological responses in the presence and absence of withaferin A were characterized by both in vitro macrophage-based assay and in vivo cytokine profiling in mice. Collectively, our results demonstrate that withaferin A selectively attenuates the pro-inflammatory signaling triggered by endotoxin without impairing other immunological pathways. This finding provides a new conceptual framework to understand the safe immune-boosting effect of W. somnifera and possibly other medicinal plants. Furthermore, the finding opens a new opportunity to facilitate the development of safe immunotherapeutic agents, such as vaccine adjuvants.

Evaluation of Indian ginseng [Withania somnifera (L.) Dunal] breeding lines and genotype-by-environment interaction across production environments in western India.

In order to find location-specific and broadly adapted genotypes for total root alkaloid content and dry root yield along with additive main effects and multiplicative interactions (AMMI) and genotype (G) main effects plus genotype × environment (E) interaction in Indian ginseng (Withania somnifera (L.) Dunal), (GGE) biplot analyses were used in the current study. Trials were carried out in a randomized complete block design (RCBD) over three succeeding years viz., 2016-2017, 2017-2018 and 2018-2019 at three different locations (S. K. Nagar, Bhiloda and Jagudan). Analysis of variance (ANOVA) for AMMI for dry root yield revealed that the environment, genotype, and GE interaction, respectively, accounted for significant sums of squares of 35.31%, 24.89%, and 32.96%. For total root alkaloid content, a significance of 27.59% of total sum of squares was justified by environment, 17.72% by genotype and 43.13% by GEI. Nine experimental trials in total were taken into consideration as contexts for the GEI analysis in 16 genotypes, including one check. AMMI analysis showed that genotypes, SKA-11, SKA-27, SKA-23 and SKA-10 were superior for mean dry root yield and SKA-11, SKA-27 and SKA-21 had better performance for total root alkaloid content across environment. The GGE biplot analysis showed genotypes SKA-11, SKA-27, SKA-10 desirable for dry root yield and SKA-26, SKA-27, SKA-11 for total root alkaloid content. As a result of the GGE and AMMI biplot techniques, SKA-11 and SKA-27 were determined to be the most desired genotypes for both total root alkaloid content and dry root yield. Further, simultaneous stability index or SSI statistics identified SKA-6, SKA-10, SKA-27, SKA-11 and AWS-1 for higher dry root yield, whilst SKA-25, SKA-6, SKA-11, SKA-12 and AWS-1 for total alkaloid content from root. Based on trait variation, GGE biplot analysis identified two mega-environments for dry root yield and a total of four for total root alkaloid content. Additionally, two representative and discriminating environments-one for dry root production and the other for total root alkaloid content were found. Location-specific and breeding for broad adaptation could be advocated for improvement and release of varieties for Indian ginseng.

Spectral reflectance and fluorescence is a rapid, non-destructive tool for drought tolerance monitoring in Withania somnifera (L.) Dunal.

Withania somnifera plants were exposed to drought stress for 23days. Relative water content (RWC), gaseous exchange, fluorescence parameters, and spectral reflectance changes were monitored under drought stress. Assimilation rate and RWC decreased by 81% and 65%, respectively, during drought exposure of 23days. Photosynthetic reflectance index (PRI) and water index (WI) showed a decreasing pattern under drought stress and correlated with Amax and RWC. Anthocyanin reflectance index and anthocyanin content increased with drought stress. Similarly, rational among R727, R696, R770, and R731 reflects chlorophyll content and Chl a/b ratio and copes with actual chlorophyll content. Fluorescence changes showed the opening and closing of PSII reaction centers, while absorbance change at 830/875nm showed activity and energy balance of PSI. Non-photochemical quenching increased under drought, which showed depoxydation of xanthine cycle pigment. Energy balance at the acceptor and donor side of PSI adjusted under drought stress by increasing electron carrying limitation at donor side. Energy balance between PSI and PSII is maintained by increasing cyclic electron flux under mild drought stress. Both protective mechanism depoxydation of xanthine cycle pigment and enhancement of cyclic electron flux reduced or diminished under severe drought stress. Decrease in leaf area and stomatal closure may cause a reduction in transpiration that results into loss of RWC and altered physiological processes. Since fluorescence, absorbance change and spectral reflectance are non-invasive measurements that may be used as indicators for assessing drought tolerance in medicinal plants.

Genetic diversity and future prospects in Withania somnifera (L.) Dunal: an assessment based on quantitative traits in different accessions of Ashwagandha

Genetic diversity and future prospects in Withania somnifera (L.) Dunal: an assessment based on quantitative traits in different accessions of Ashwagandha

Formulation and evaluation of hydrogel for topical drug delivery of Zingiber officinale Rosc. and Withania somnifera (L.) Dunal to increase the bioavailability of oils for the treatment of arthritis

Formulation and evaluation of hydrogel for topical drug delivery of Zingiber officinale Rosc. and Withania somnifera (L.) Dunal to increase the bioavailability of oils for the treatment of arthritis

An updated review on phytochemistry and molecular targets of Withania somnifera (L.) Dunal (Ashwagandha).

Withania somnifera (L.) Dunal belongs to the nightshade family Solanaceae and is commonly known as Ashwagandha. It is pharmacologically a significant medicinal plant of the Indian sub-continent, used in Ayurvedic and indigenous systems of medicine for more than 3,000years. It is a rich reservoir of pharmaceutically bioactive constituents known as withanolides (a group of 300 naturally occurring C-28 steroidal lactones with an ergostane-based skeleton). Most of the biological activities of W. somnifera have been attributed to two key withanolides, namely, withaferin-A and withanolide-D. In addition, bioactive constituents such as withanosides, sitoindosides, steroidal lactones, and alkaloids are also present with a broad spectrum of therapeutic potential. Several research groups worldwide have discovered various molecular targets of W. somnifera, such as inhibiting the activation of nuclear factor kappa-B and promoting apoptosis of cancer cells. It also enhances dopaminergic D2 receptor activity (relief in Parkinson's disease). The active principles such as sitoindosides VII-X and withaferin-A possess free radical properties. Withanolide-D increases the radio sensitivity of human cancer cells via inhibiting deoxyribonucleic acid (DNA) damage to non-homologous end-joining repair (NHEJ) pathways. Withanolide-V may serve as a potential inhibitor against the main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to combat COVID. The molecular docking studies revealed that the withanolide-A inhibits acetyl-cholinesterase in the brain, which could be a potential drug to treat Alzheimer's disease. Besides, withanolide-A reduces the expression of the N-methyl-D-aspartate (NMDA) receptor, which is responsible for memory loss in epileptic rats. This review demonstrates that W. somnifera is a rich source of withanolides and other bioactive constituents, which can be used as a safe drug for various chronic diseases due to the minimal side effects in various pre-clinical studies. These results are interesting and signify that more clinical trials should be conducted to prove the efficacy and other potential therapeutic effects in human settings.

Nootropic Herbs, Shrubs, and Trees as Potential Cognitive Enhancers.

Plant-based nootropics are a diverse group of natural drugs that can improve cognitive abilities through various physiological mechanisms, especially in cases where these functions are weakened or impaired. In many cases, the nootropics enhance erythrocyte plasticity and inhibit aggregation, which improves the blood's rheological properties and increases its flow to the brain. Many of these formulations possess antioxidant activity that protects brain tissue from neurotoxicity and improves the brain's oxygen supply. They can induce the synthesis of neuronal proteins, nucleic acids, and phospholipids for constructing and repairing neurohormonal membranes. These natural compounds can potentially be present in a great variety of herbs, shrubs, and even some trees and vines. The plant species reviewed here were selected based on the availability of verifiable experimental data and clinical trials investigating potential nootropic effects. Original research articles, relevant animal studies, meta-analyses, systematic reviews, and clinical trials were included in this review. Selected representatives of this heterogeneous group included Bacopa monnieri (L.) Wettst., Centella asiatica (L.) Urban, Eleutherococcus senticosus (Rupr. & Maxim.) Maxim., Ginkgo biloba L., Lepidium meyenii Walp., Panax ginseng C.A. Meyer, Paullinia cupana Kunth, Rhodiola rosea L., Schisandra chinensis (Turcz.) Baill., and Withania somnifera (L.) Dunal. The species are depicted and described, together with their active components and nootropic effects, and evidence of their efficacy is presented. The study provides brief descriptions of the representative species, their occurrence, history, and the chemical composition of the principle medicinal compounds, with uses, indications, experimental treatments, dosages, possible side effects, and contraindications. Most plant nootropics must be taken at optimal doses for extended periods before measurable improvement occurs, but they are generally very well tolerated. Their psychoactive properties are not produced by a single molecule but by a synergistic combination of several compounds. The available data suggest that including extracts from these plants in medicinal products to treat cognitive disorders can have substantial potential therapeutic benefits.

Pharmacological potential of Withania somnifera (L.) Dunal and Tinospora cordifolia (Willd.) Miers on the experimental models of COVID-19, T cell differentiation, and neutrophil functions.

Cytokine release syndrome (CRS) due to severe acute respiratory coronavirus-2 (SARS-CoV-2) infection leads to life-threatening pneumonia which has been associated with coronavirus disease (COVID-19) pathologies. Centuries-old Asian traditional medicines such as Withania somnifera (L.) Dunal (WS) and Tinospora cordifolia (Willd.) Miers (TC) possess potent immunomodulatory effects and were used by the AYUSH ministry, in India during the COVID-19 pandemic. In the present study, we investigated WS and TC's anti-viral and immunomodulatory efficacy at the human equivalent doses using suitable in vitro and in vivo models. While both WS and TC showed immuno-modulatory potential, WS showed robust protection against loss in body weight, viral load, and pulmonary pathology in the hamster model of SARS-CoV2. In vitro pretreatment of mice and human neutrophils with WS and TC had no adverse effect on PMA, calcium ionophore, and TRLM-induced ROS generation, phagocytosis, bactericidal activity, and NETs formation. Interestingly, WS significantly suppressed the pro-inflammatory cytokines-induced Th1, Th2, and Th17 differentiation. We also used hACE2 transgenic mice to further investigate the efficacy of WS against acute SARS-CoV2 infection. Prophylactic treatment of WS in the hACE2 mice model showed significant protection against body weight loss, inflammation, and the lung viral load. The results obtained indicate that WS promoted the immunosuppressive environment in the hamster and hACE2 transgenic mice models and limited the worsening of the disease by reducing inflammation, suggesting that WS might be useful against other acute viral infections. The present study thus provides pre-clinical efficacy data to demonstrate a robust protective effect of WS against COVID-19 through its broader immunomodulatory activity.

Effect of Different Organic Sources of Nutrients on Quality and Economics of Ashwagandha [Withania somnifera (L.) Dunal

The present investigation entitled Effect of different organic sources of nutrients on quality and economics of ashwagandha [Withania somnifera (L.) Dunal] was carried out during Kharif 2021-22 at College Farm, College of Horticulture, Sardarkrushinagar Dantiwada Agricultural University, Jagudan, Dist. Mehsana, Gujarat. Experiment was laid out in randomized block design with three replications and twenty treatments viz., T1: 100% RDN through FYM; T2: 100% RDN through Vermicompost; T3: 100% RDN through Neem cake; T4: 100% RDN through Poultry manure; T5: 80% RDN through FYM; T6: 80% RDN through Vermicompost; T7: 80% RDN through Neem cake; T8: 80% RDN through Poultry manure; T9: 60% RDN through FYM; T10: 60% RDN through Vermicompost; T11: 60% RDN through Neem cake; T12: 60% RDN through Poultry manure; T13: 80% RDN through FYM + Azotobacter + KSM + PSB; T14: 80% RDN through Vermicompost + Azotobacter + KSM + PSB; T15: 80% RDN through Neem cake+ Azotobacter + KSM + PSB; T16: 80% RDN through Poultry manure + Azotobacter + KSM + PSB; T17: 60% RDN through FYM + Azotobacter + KSM + PSB; T18: 60% RDN through Vermicompost + Azotobacter + KSM + PSB; T19: 60% RDN through Neem cake + Azotobacter + KSM + PSB; T20: 60% RDN through Poultry manure + Azotobacter + KSM + PSB. Maximum chlorophyll a, b and total at 90 DAS (at full bloom stage) (1.92, 0.75 and 2.11 mg/g, respectively) and withanolides content (0.32%) at harvest were recorded with treatment T16. The maximum net income (₹ 1,38,707/ha) and benefit cost ratio (3.52) were also obtained in same treatment. Therefore, it can be concluded that the application of 80% RDN through poultry manure + Azotobacter + KSM + PSB (T16) was found beneficial for obtaining higher yield of better quality and economic returns in ashwagandha.

Chemical, microbial and safety profiling of a standardized Withania somnifera (Ashwagandha) extract and Withaferin A, a potent novel phytotherapeutic of the millennium

Background:Withania somnifera (L.) Dunal, popularly known as Ashwagandha, is an ethnomedicinal plant with multiple pharmacotherapeutic applications. The diverse medicinal properties of the plant are largely due to the presence of withanolides, a group of C28 ergostane based steroidal lactones, with several sites of unsaturation and oxygenation. Withaferin A, a major with anolide present in Ashwagandha plant accounts for its emerging new roles to treat cancer, arthritis, inflammatory responses, immunomodulatory properties, and neuronal disorders. The root and leaf extracts are specifically important constituent materials for the development of phytotherapeutics, mostly intended for oral consumption. Several studies have been carried out to delineate the toxic manifestations of the extract for human consumption.Objective:Establish the broad-spectrum safety of W-ferinAmax ashwagandha (WFA).Study: This investigation demonstrated a novel, standardized W-ferinAmax ashwagandha (WFA) extraction technology from the whole herb of Withania sominfera, conducted HPLC analysis to identify the constituents, detected the heavy metals, microbiological contaminants, pesticides contaminants, and safety profile.Results:A novel extraction technology was employed to obtain WFA from the whole plant of Withania sominfera. HPLC analysis revealed that WFA contains a total of 15.4% Withanolides. In particular, Withaferin A, Withanoside IV, and Withanolide A contents were 6.469%, 1.022%, and 0.073%, respectively. The extract contained only 0.403 ppm of heavy metals out of which traces of arsenic, mercury and lead were detected, and cadmium was absent. USP recommended 80 residue basic pesticide screen indicated that the extraction was safe for human consumption. It was also found to be free from pathogenic microbes as assessed by the absence of E. coli and other coliforms, Salmonella and Staphylococcus species.Conclusion: The data generated cumulatively indicated that WFA is safe for further downstream processing to and for human consumption.Keywords: Ashwagandha, Withaferin A, phytotherapeutics, material safety; heavy metals; pesticides

The immunomodulatory role of withania somnifera (L.) dunal in inflammatory diseases.

Withania somnifera (L.) Dunal (Solanaceae) (also known as Ashwagandha) is a botanical drug that has been used for centuries to treat many chronic diseases like high blood pressure, arthritis, diabetes, Alzheimer's disease, and depression. As many botanical drugs, w. Somnifera possesses anti-inflammatory, antioxidant, anticarinogenic, anti-diabetic, and anti-asthmatic properties. W. somnifera is often compared to the ginseng plant due to its ability to reduce stress, improve cognitive functions (e.g., memory), and promote a healthy immune system. It promotes immunomodulatory effects whose function is to balance the humoral and cellular responses of the adaptive immune system. The therapeutic effect of w. Somnifera is attributed to active ingredients like alkaloids, steroidal lactones (such as withanolides, withaferins), and steroidal saponins. Although w. Somnifera is safe and highly recommended for treating various diseases, the current knowledge and understanding of its operational mechanisms are limited. One of the proposed mechanisms states that w. Somnifera promotes cellular-mediated immunity or initiates chemical interactions that contribute to therapeutic effects. Withania somnifera has been shown to play a significant role in immunological diseases by modulating several cytokines, increasing T-cell proliferation and enhancing macrophages functions. In this review, we will discuss the latest therapeutic effects of w. Somnifera on a number of diseases through modulating immunological markers and which specific components of w. Somnifera induce these therapeutic activities. We will also focus on the chemical properties in w. Somnifera components and their immunomodulatory role in type 2 allergic diseases where type 2 inflammation is highly imbalanced.

In Silico Study on the Interactions, Molecular Docking, Dynamics and Simulation of Potential Compounds from Withania somnifera (L.) Dunal Root against Cancer by Targeting KAT6A.

Cancer is characterized by the abnormal development of cells that divide in an uncontrolled manner and further take over the body and destroy the normal cells of the body. Although several therapies are practiced, the demand and need for new therapeutic agents are ever-increasing because of issues with the safety, efficacy and efficiency of old drugs. Several plant-based therapeutics are being used for treatment, either as conjugates with existing drugs or as standalone formulations. Withania somnifera (L.) Dunal is a highly studied medicinal plant which is known to possess immunomodulatory activity as well as anticancer properties. The pivotal role of KAT6A in major cellular pathways and its oncogenic nature make it an important target in cancer treatment. Based on the literature and curated datasets, twenty-six compounds from the root of W. somnifera and a standard inhibitor were docked with the target KAT6A using Autodock vina. The compounds and the inhibitor complexes were subjected to molecular dynamics simulation (50 ns) using Desmond to understand the stability and interactions. The top compounds (based on the docking score of less than -8.5 kcal/mol) were evaluated in comparison to the inhibitor. Based on interactions at ARG655, LEU686, GLN760, ARG660, LEU689 and LYS763 amino acids with the inhibitor WM-8014, the compounds from W. somnifera were evaluated. Withanolide D, Withasomniferol C, Withanolide E, 27-Hydroxywithanone, Withanolide G, Withasomniferol B and Sitoindoside IX showed high stability with the residues of interest. The cell viability of human breast cancer MCF-7 cells was evaluated by treating them with W. Somnifera root extract using an MTT assay, which showed inhibitory activity with an IC50 value of 45 µg/mL. The data from the study support the traditional practice of W. somnifera as an anticancer herb.

Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal.

Cancer represents the second most deadly disease and one of the most important public health concerns worldwide. Surgery, chemotherapy, radiation therapy, and immune therapy are the major types of treatment strategies that have been implemented in cancer treatment. Unfortunately, these treatment options suffer from major limitations, such as drug-resistance and adverse effects, which may eventually result in disease recurrence. Many phytochemicals have been investigated for their antitumor efficacy in preclinical models and clinical studies to discover newer therapeutic agents with fewer adverse effects. Withaferin A, a natural bioactive molecule isolated from the Indian medicinal plant Withania somnifera (L.) Dunal, has been reported to impart anticancer activities against various cancer cell lines and preclinical cancer models by modulating the expression and activity of different oncogenic proteins. In this article, we have comprehensively discussed the biosynthesis of withaferin A as well as its antineoplastic activities and mode-of-action in in vitro and in vivo settings. We have also reviewed the effect of withaferin A on the expression of miRNAs, its combinational effect with other cytotoxic agents, withaferin A-based formulations, safety and toxicity profiles, and its clinical potential.

Exploration and sustainable utilization of medicinal plants of Dhar forests of Madhya Pradesh

Abstract BACKGROUND: This article deals with the pharmaceutically important medicinal plants from Dhar forest divisions of Madhya Pradesh. Exploration of Dhar forest division has been carried out during September, 2017. The study was conducted to prepare records of medicinal plants in the study areas which has not yet been explored thoroughly covering the present parameters described in the manuscript. METHODS: Exploration of pharmaceutically important medicinal plants in Dhar Forest Division has been made with a details of geographical location and potential of these plants. The collected plants were processed for documentation by preparing herbarium sheets, identification accession, and deposition in the herbarium of the Institute. RESULTS: The important medicinal plants namely Adensonia digitata L., Actiniopteris radiata (Sw.) Link, Aegle marmelos (L.) Correa., Boswellia serrata Roxb., Celastrus paniculata Willd., Commiphora madagascarensis Jacq., Helicteres isora Planch., Holarrhena pubescens Wall. ex G. Don, Justicia adhatoda L., Marsdenia tenacissima (Roxb.) Moon, Oroxylum indicum (L.) Kurz, Ougenia oogenesis (Roxb.) Hochr. Pleurolobus gangeticus (L.) J.St.-Hil. ex H. Ohashi & K. Ohashi, Solanum nigrum L., S. incanum L., Telosma pallida (Roxb.) Carib., Terminalia bellirica (Gaertn.) Roxb., etc. were recorded which can be undertaken for mass cultivation by the farmers by adding some other medicinal plants having commercial value viz. Celastrus paniculatus Willd., Marsdenia tenacissima (Roxb.) Moon., Withania somnifera (L.) Dunal, etc. CONCLUSION: The study area is widely occupied by plants of Actiniopteris radiata, Boswelia serrata Roxb., Holarrhena pubescens Wall. ex G. Donand Vitex negundo L. for commercialization whereas plants of Marsdenia tenacissima (Roxb.) Moon, Oroxylum indicum (L.) Kurz etc. need conservation and protection in the habitat.

Withania somnifera-derived carbon dots protect human epidermal cells against UVB-induced cell death and support growth factor-mediated wound healing.

Solar radiation comprising UVA and UVB regions is considered a skin-damaging factor inducing inflammation, oxidative stress, hyperpigmentation, and photo-aging. Photoluminescent carbon dots (CDs) were synthesized from the root extract of a Withania somnifera (L.) Dunal plant and urea, using a one-step microwave method. These Withania somnifera CDs (wsCDs) were 14.4 ± 0.18 d nm in diameter and presented photoluminescence. UV absorbance showed the presence of π-π* (C[double bond, length as m-dash]C) and n-π* (C[double bond, length as m-dash]O) transition regions in wsCDs. FTIR analysis indicated the presence of nitrogen and carboxylic functional groups on the surface of wsCDs. HPLC analysis of wsCDs showed the presence of withanoside IV, withanoside V, and withanolide A. The wsCDs were found to be biocompatible in human skin epidermal (A431) cells and hindered UVB irradiation-induced loss of metabolic activity and oxidative stress. The wsCDs supported rapid dermal wound healing through augmented TGF-β1 and EGF gene expression levels in A431 cells. Finally, wsCDs were found to be biodegradable through a myeloperoxidase-catalyzed peroxidation reaction. The study concluded that under in vitro conditions, Withania somnifera root extract-derived biocompatible carbon dots provided photo-protection against UVB-stimulated epidermal cell damage and supported rapid wound healing.

Experimental evidence to the untapped potential of Ayurvedic herb, Ashwagandha: Bench-to-Bedside

ABSTRACT The last century has witnessed a major transition in every aspect of human life. Advancement in science and technologies, health, agriculture and medical sectors have tremendously improved food and living standards. A significant surge in human life expectancy has resulted in an increase in aging society triggering alters in global population demographics, social, and health-care supporting systems. Industrialization of lifestyle with excessive use of chemicals has sparked another negative feedback loop, threatening quality of life (QOL), and increasing sense of stress and anxiety. Together, these scenarios have posed new challenges to manage age- and stress-related ailments and maintain good QOL. Traditional home medicine systems, in contrast to use of chemicals/drugs, depending on the use of natural resources/ways to boost our built-in defense mechanisms. Ayurveda (Ayu means life and Veda means knowledge) is the world’s oldest home medicine system of Indian origin that continues to be a living tradition with a history of about ~5000 years. Ayurvedic medicine, with its deeply trusted concept of holistic approach, is based on maintaining the harmonious balance of different life-elements to treat/prevent diseases. Ayurvedic system involves the use of variety of herbs/plants, yoga, and relaxation techniques. Among a large number of plants described to enhance QOL in Ayurveda, Ashwagandha (Withania somnifera (L.) Dunal) categorized as Rasayana (a rejuvenating herb) is also appraised as “Queen of Ayurveda”. In this review, we discuss the experimental evidence of the therapeutic activities of Ashwagandha and its untapped potential for the treatment of stress, brain ailments, cancer and COVID-19.