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.

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Withania somnifera (L.) Dunal: Opportunity for Clinical Repurposing in COVID-19 Management

Vivek K Kashyap1,2, Anupam Dhasmana1,2, Murali M Yallapu1,2, Subhash C Chauhan1,2 & Meena Jaggi*,1,2 1Department of Immunology & Microbiology, School of Medicine, The University of Texas Rio Grande Valley, McAllen, TX 78504, USA 2South Texas Center of Excellence in Cancer Research, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX 78504, USA *Author for correspondence: Tel.: +1 956 296 2008; meena.jaggi@utrgv.edu

/pdf/withania-somnifera-as-a-potential-future-drug-molecule-for-53g24qvzkh.pdf

Withania somnifera as a potential future drug molecule for COVID-19.

In 2020, a novel strain of coronavirus (COVID-19) has led to a significant morbidity and mortality worldwide As of the date of this writing, a total of 116 M cases has been diagnosed worldwide leading to 25 M deaths The number of mortalities is directly correlated with the rise of innate immune cells (especially macrophages) in the lungs that secrete inflammatory cytokines (IL-1β and IL-6) leading to the development of "Cytokine Storm Syndrome" (CSS), multi-organ-failure and death Given that currently the treatment of this condition is rare and release of effective vaccine might be months away, here, we review the plants and their pharmacologically active-compounds as potential phytopharmaceuticals for the virus induced inflammatory response Experimental validation of the effectiveness of these natural compounds to prevent or reduce the cytokine storm might be beneficial as an adjunct treatment of SARS-CoV-2

Phytotherapy for treatment of cytokine storm in COVID-19.

Withania somnifera (L.) Dunal: Phytochemistry, structure-activity relationship, and anticancer potential.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological agent of the potentially fatal coronavirus disease 2019 (COVID-19), has currently affected over 87 million people with worldwide deaths nearing 1 9 million Amidst the developing vaccines and effective therapies, there is a need to develop alternative and supportive strategies for ameliorating the effects of SARS-CoV-2 infections in humans and treat COVID-19 patients Several medicinal plants and herbs contain useful phytochemicals, which are being explored to develop medicines and drugs to counter the COVID-19 pandemic Withania somnifera is a medicinal herb of growing importance that is extensively utilized in Ayurveda The medicinal attributes of W somnifera are owing to a broad range of bioactive secondary metabolites including steroidal lactones [withanone, withanolide D, withanolide A, and withaferin A (WFA)] Among these, WFA is one of the most interesting naturally occurring bioactive compounds that possess potent anti-tumorigenic, antiinflammatory, pro-apoptotic, anti-angiogenic, and anti-invasive activities It might bind to SARS-CoV-2 S protein and alter the S protein, thereby hindering its access into the host cells Withanone and Withanoside V can impede the functional activities of SARS-CoV-2 main protease (Mpro) Withanolides have been found to control cytokine secretions during infection and could alleviate the cytokine storm in the lungs The combined use of withanolides are several other drugs or therapeutic modalities, such as hydroxychloroquine and dexamethasone, has been demonstrated as an efficient strategy to improve the effectiveness of standard chemotherapy or design a robust therapeutic regime for COVID-19 treatment Nevertheless, exhaustive research efforts are required to explore the anti-inflammatory and immunomodulatory potentialities of withanolides for alleviating the severity of the disease during SARS-CoV-2 infections This review highlights the medicinal and therapeutic potential of withanolides against COVID-19 © 2021 Manish Dhawan et al This is an open access article distributed under the terms of the Creative Commons Attribution 4 0 International License (https://creativecommons org/licenses/by/4 0/)

/pdf/medicinal-and-therapeutic-potential-of-withanolides-from-8uvmadx8ob.pdf

Medicinal and therapeutic potential of withanolides from Withania somnifera against COVID-19

Withania somnifera, commonly known as “Ashwagandha” or “Indian ginseng” is an essential therapeutic plant of Indian subcontinent regions. It is regularly used, alone or in combination with other pl...

Pharmacological evaluation of Ashwagandha highlighting its healthcare claims, safety, and toxicity aspects.

Ulcerative colitis (UC) is a chronic inflammatory bowel condition considered by oxido-nitrosative stress and the release of pro-inflammatory cytokines that affects the mucosal lining of the colon. ...

Protective effect of sarsasapogenin in TNBS induced ulcerative colitis in rats associated with downregulation of pro-inflammatory mediators and oxidative stress

Atopic dermatitis (AD) is a pruritic, chronic, relapsing inflammatory skin disease. The research aims to study the effects of Sarsasapogenin and its combination with Fluticasone in 2, 4-Dinitrofluo...

Sarsasapogenin and fluticasone combination improves DNFB induced atopic dermatitis lesions in BALB/c mice.

The most common principal malignant tumor that accounts for ∼80% of cases of liver cancer across the world is hepatocellular carcinoma (HCC). It is a multifacetedillness that is caused by several risk factors and often progresses in the context of underlying cirrhosis. It is tremendously difficult and essential for the screening of novel therapeutic medications to establish HCC preclinical models that are equivalent to clinical diseases settings, i.e., representing the tumor microenvironment of HCC. In the progress of HCC, numerous molecular cascades have been supposed to play a part. Sorafenib is the only drug permitted by the US Food and Drug Administration for the treatment of HCC. Yet because of the increasing resistance to the drug and its toxicity, clinical treatment methods are not completely adequate. Newer treatment therapy options are essential for the management of HCC in patients. Natural compounds can be afforded by the patients with improved results with less toxicity and fewer side effects, among different methods of liver cancer treatment. The treatment and management of HCC with natural drugs and their phytoconstituents are connected to several paths that can prevent the occurrence and progress of HCC in several ways. The present review summarizes the etiology of HCC, molecular pathways, newer therapeutic approaches, natural dietary products, herbal plants and phytoconstituents for HCC treatment.

Deepa S. Mandlik

Papers

Pharmacological evaluation of Ashwagandha highlighting its healthcare claims, safety, and toxicity aspects.

Protective effect of sarsasapogenin in TNBS induced ulcerative colitis in rats associated with downregulation of pro-inflammatory mediators and oxidative stress

Sarsasapogenin and fluticasone combination improves DNFB induced atopic dermatitis lesions in BALB/c mice.

An Overview of Hepatocellular Carcinoma with Emphasis on Dietary Products and Herbal Remedies.

Nephroprotective role of diosgenin in gentamicin-induced renal toxicity: biochemical, antioxidant, immunological and histopathological approach