Withania somnifera: Ethnobotany, Pharmacology, and Therapeutic Functions
01 Jan 2017-pp 137-154
TL;DR: Ethnobotanical and pharmacologic characteristics and therapeutic applications of the plant and its active constituents are recapitulate.
Abstract: Withania somnifera , also known as ashwagandha, is one of the prominent medicinal plants in Indian systems of medicine. Since antiquity, it is used against myriad of clinical conditions and, in fact, its history of use as a medicine dates back to AD 6000. The plant contains a range of different classes of chemical constituents such as alkaloids, steroidal lactones, and flavonoids. These chemical moieties are responsible for various biological activities of the plant. Laboratory studies demonstrated the plant to be antiinflammatory, antitumor, neuroprotective, antimicrobial, antistress, antidiabetic, and cardioprotective. These pharmacologic activities are in part due to the capability of W. somnifera to reduce reactive oxygen species, modulate mitochondrial function, regulate apoptosis, reduce inflammation, and enhance endothelial function. Additionally, it has been used singly or in combination against various diseases of humans. Here, we recapitulate ethnobotanical and pharmacologic characteristics and therapeutic applications of the plant and its active constituents.
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TL;DR: The study suggests that Withanoside V in Ashwagandha may be serve as a potential inhibitor against Mpro of SARS-CoV-2 to combat COVID-19 and may have an antiviral effect on nCoV.
Abstract: SARS-CoV-2 is the causative agent of COVID-19 and has been declared as pandemic disease by World Health Organization. Lack of targeted therapeutics and vaccines for COVID-2019 have triggered the sc...
91 citations
TL;DR: Molecular mechanism of various plant‐based interventions screened for cardioprotective effect in ISP‐induced cardiotoxicity, myocardial ischemia, and cardiac fibrosis is surveyed and their probable mechanistic profile is summarized.
Abstract: Heart is the most active and incumbent organ of the body, which maintains blood flow, but due to various pathological reasons, several acute and chronic cardiac complications arise out of which myocardial infarction is one of the teething problems. Isoproterenol (ISP)-induced myocardial ischemia is a classical model to screen the cardioprotective effects of various pharmacological interventions. Phytochemicals present a novel option for treating various human maladies including those of the heart. A large number of plant products and their active ingredients have been screened for efficacy in ameliorating ISP-induced myocardial ischemia including coriander, curcumin, Momordica, quercetin, and Withania somnifera. These phytochemicals constituents may play key role in preventing disease and help in cardiac remodeling. Reactive oxygen species scavenging, antiinflammatory, and modulation of various molecular pathways such as Nrf2, NFкB, p-21 activated kinase 1 (PAK1), and p-smad2/3 signaling modulation have been implicated behind the claimed protection. In this review, we have provided a focused overview on the utility of ISP-induced cardiotoxicity, myocardial ischemia, and cardiac fibrosis for preclinical research. In addition, we have also surveyed molecular mechanism of various plant-based interventions screened for cardioprotective effect in ISP-induced cardiotoxicity, and their probable mechanistic profile is summarized.
72 citations
Cites background from "Withania somnifera: Ethnobotany, Ph..."
...Its extract and withaferin A is reported for beneficial role in various diseases such as fibrosis, debility, and also used as general health tonic (Sengupta et al., 2018; Nasimi Doost Azgomi et al., 2018; Ahmad & Dar, 2018; Bale, Venkatesh, Sunkoju, & Godugu, 2018)....
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TL;DR: A compelling case is made to evaluate the potential of these Rasayana botanicals in the management of COVID-19 following rigorous experimental validation and predictive tools indicate that there would beneficial herb-drug pharmacokinetic-pharmacodynamic interactions with concomitantly administered drug therapy.
Abstract: The Coronavirus disease (COVID-19) caused by the virus SARS-CoV-2 has become a global pandemic in a very short time span. Currently, there is no specific treatment or vaccine to counter this highly contagious disease. There is an urgent need to find a specific cure for the disease and global efforts are directed at developing SARS-CoV-2 specific antivirals and immunomodulators. Ayurvedic Rasayana therapy has been traditionally used in India for its immunomodulatory and adaptogenic effects, and more recently has been included as therapeutic adjuvant for several maladies. Amongst several others, Withania somnifera (Ashwagandha), Tinospora cordifolia (Guduchi) and Asparagus racemosus (Shatavari) play an important role in Rasayana therapy. The objective of this study was to explore the immunomodulatory and anti SARS-CoV2 potential of phytoconstituents from Ashwagandha, Guduchi and Shatavari using network pharmacology and docking. The plant extracts were prepared as per ayurvedic procedures and a total of 31 phytoconstituents were identified using UHPLC-PDA and mass spectrometry studies. To assess the immunomodulatory potential of these phytoconstituents an in-silico network pharmacology model was constructed. The model predicts that the phytoconstituents possess the potential to modulate several targets in immune pathways potentially providing a protective role. To explore if these phytoconstituents also possess antiviral activity, docking was performed with the Spike protein, Main Protease and RNA dependent RNA polymerase of the virus. Interestingly, several phytoconstituents are predicted to possess good affinity for the three targets, suggesting their application for the termination of viral life cycle. Further, predictive tools indicate that there would not be adverse herb-drug pharmacokinetic-pharmacodynamic interactions with concomitantly administered drug therapy. We thus make a compelling case to evaluate the potential of these Rasayana botanicals as therapeutic adjuvants in the management of COVID-19 following rigorous experimental validation.
46 citations
TL;DR: In this article, the authors presented a research synthesis of in silico, in vitro, in vivo, and clinical studies on Withania somnifera (L.) Dunal (WS) and discussed its potential for prophylaxis and management of COVID-19.
Abstract: As the COVID-19 pandemic is progressing, the therapeutic gaps in conventional management have highlighted the need for the integration of traditional knowledge systems with modern medicine. Ayurvedic medicines, especially Ashwagandha (Withania somnifera (L.) Dunal, WS), may be beneficial in the management of COVID-19. WS is a widely prescribed Ayurvedic botanical known as an immunomodulatory, antiviral, anti-inflammatory, and adaptogenic agent. The chemical profile and pharmacological activities of WS have been extensively reported. Several clinical studies have reported its safety for use in humans. This review presents a research synthesis of in silico, in vitro, in vivo, and clinical studies on Withania somnifera (L.) Dunal (WS) and discusses its potential for prophylaxis and management of COVID-19. We have collated the data from studies on WS that focused on viral infections (HIV, HSV, H1N1 influenza, etc.) and noncommunicable diseases (hypertension, diabetes, cancer, etc.). The experimental literature indicates that WS has the potential for 1) maintaining immune homeostasis, 2) regulating inflammation, 3) suppressing pro-inflammatory cytokines, 4) organ protection (nervous system, heart, lung, liver, and kidney), and 5) anti-stress, antihypertensive, and antidiabetic activities. Using these trends, the review presents a triangulation of Ayurveda wisdom, pharmacological properties, and COVID-19 pathophysiology ranging from viral entry to end-stage acute respiratory distress syndrome (ARDS). The review proposes WS as a potential therapeutic adjuvant for various stages of COVID-19 management. WS may also have beneficial effects on comorbidities associated with the COVID-19. However, systematic studies are needed to realize the potential of WS for improving clinical outcome of patients with COVID-19.
39 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
References
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TL;DR: An overview of the chemical structures of triterpenoid components and their biological activity is presented, focusing on two novel activities, tumor inhibition and antiangiogenic properties of withaferin A and the effects of withanolide A on Alzheimer's disease.
Abstract: Withania somnifera, commonly known as Ashwagandha, is an important medicinal plant that has been used in Ayurvedic and indigenous medicine for over 3,000 years. In view of its varied therapeutic potential, it has also been the subject of considerable modern scientific attention. The major chemical constituents of the Withania genus, the withanolides, are a group of naturally occurring C28-steroidal lactone triterpenoids built on an intact or rearranged ergostane framework, in which C-22 and C-26 are appropriately oxidized to form a six-membered lactone ring. In recent years, numerous pharmacological investigations have been carried out into the components of W. somnifera extracts. We present here an overview of the chemical structures of triterpenoid components and their biological activity, focusing on two novel activities, tumor inhibition and antiangiogenic properties of withaferin A and the effects of withanolide A on Alzheimer's disease. The most recent attempts in biotechnological production of withanolides are also discussed.
470 citations
TL;DR: Withania somnifera (WS) is an anti-inflammatory and anti-arthritic agent and was found useful in clinical cases of Rheumatoid and Osteoarthritis and neurodegenerative diseases such as Parkinson's, Huntington's and Alzeimer's diseases.
Abstract: Withania somnifera (Ashawagandha) is very revered herb of the Indian Ayurvedic system of medicine as a Rasayana (tonic). It is used for various kinds of disease processes and specially as a nervine tonic. Considering these facts many scientific studies were carried out and its adaptogenic / anti-stress activities were studied in detail. In experimental models it increases the stamina of rats during swimming endurance test and prevented adrenal gland changes of ascorbic acid and cortisol content produce by swimming stress. Pretreatment with Withania somnifera (WS) showed significance protection against stress induced gastric ulcers. WS have anti-tumor effect on Chinese Hamster Ovary (CHO) cell carcinoma. It was also found effective against urethane induced lung-adenoma in mice. In some cases of uterine fibroids, dermatosarcoma, long term treatment with WS controlled the condition. It has a Cognition Promoting Effect and was useful in children with memory deficit and in old age people loss of memory. It was also found useful in neurodegenerative diseases such as Parkinson’s, Huntington’s and Alzeimer’s diseases. It has GABA mimetic effect and was shown to promote formation of dendrites. It has anxiolytic effect and improves energy levels and mitochondrial health. It is an anti-inflammatory and anti-arthritic agent and was found useful in clinical cases of Rheumatoid and Osteoarthritis. Large scale studies are needed to prove its clinical efficacy in stress related disorders, neuronal disorders and cancers.
348 citations
TL;DR: It is shown that withaferin A inhibits human umbilical vein endothelial cell (HUVEC) sprouting in three-dimensional collagen-I matrix at doses which are relevant to NF-kappa B-inhibitory activity and is shown to exert potent anti-angiogenic activity in vivo at doses that are 500-fold lower than those previously reported to exert anti-tumor activity in vitro.
Abstract: The medicinal plant Withania somnifera is widely researched for its anti-inflammatory, cardioactive and central nervous system effects. In Ayurveda, the major Traditional Indian medicine system, extracts from W. somnifera are distinctively employed for the treatment of arthritis and menstrual disorders. Because these conditions involve angiogenic processes we hypothesized that the W. somnifera extracts might contain angiogenesis inhibitors. We employed an endothelial cell-sprouting assay to monitor the purification of substances from W. somnifera root extracts and isolated as the active principle the previously known natural product withaferin A. We show that withaferin A inhibits human umbilical vein endothelial cell (HUVEC) sprouting in three-dimensional collagen-I matrix at doses which are relevant to NF-kappa B-inhibitory activity. Withaferin A inhibits cell proliferation in HUVECs (IC50=12 nM) at doses that are significantly lower than those required for tumor cell lines through a process associated with inhibition of cyclin D1 expression. We propose that the inhibition of NF-kappa B by withaferin A in HUVECs occurs by interference with the ubiquitin-mediated proteasome pathway as suggested by the increased levels of poly-ubiquitinated proteins. Finally, withaferin A is shown to exert potent anti-angiogenic activity in vivo at doses that are 500-fold lower than those previously reported to exert anti-tumor activity in vivo. In conclusion, our findings identify a novel mode of action of withaferin A, which highlights the potential use of this natural product for cancer treatment or prevention.
335 citations
TL;DR: The remarkable therapeutic effect of W. somnifera mediated through up-regulation of liver LRP indicates that targeting the periphery offers a unique mechanism for Aβ clearance and reverses the behavioral deficits and pathology seen in Alzheimer's disease models.
Abstract: A 30-d course of oral administration of a semipurified extract of the root of Withania somnifera consisting predominantly of withanolides and withanosides reversed behavioral deficits, plaque pathology, accumulation of beta-amyloid peptides (A beta) and oligomers in the brains of middle-aged and old APP/PS1 Alzheimer's disease transgenic mice. It was similarly effective in reversing behavioral deficits and plaque load in APPSwInd mice (line J20). The temporal sequence involved an increase in plasma A beta and a decrease in brain A beta monomer after 7 d, indicating increased transport of A beta from the brain to the periphery. Enhanced expression of low-density lipoprotein receptor-related protein (LRP) in brain microvessels and the A beta-degrading protease neprilysin (NEP) occurred 14-21 d after a substantial decrease in brain A beta levels. However, significant increase in liver LRP and NEP occurred much earlier, at 7 d, and were accompanied by a rise in plasma sLRP, a peripheral sink for brain A beta. In WT mice, the extract induced liver, but not brain, LRP and NEP and decreased plasma and brain A beta, indicating that increase in liver LRP and sLRP occurring independent of A beta concentration could result in clearance of A beta. Selective down-regulation of liver LRP, but not NEP, abrogated the therapeutic effects of the extract. The remarkable therapeutic effect of W. somnifera mediated through up-regulation of liver LRP indicates that targeting the periphery offers a unique mechanism for A beta clearance and reverses the behavioral deficits and pathology seen in Alzheimer's disease models.
297 citations
TL;DR: The immunomodulatory activities of an Indian Ayurvedic medicinal preparation, i.e. WST and WS2, were studied in mice for immune inflammation: active paw anaphylaxis and delayed type hypersensitivity (DTH), revealing a significant increase in white blood cell counts and platelet counts.
235 citations