Prevention of acute graft-versus-host-disease by Withaferin a via suppression of AKT/mTOR pathway

Mehta, Miten; Gohil, Dievya; Khattry, Navin; Kumar, Rajiv; Sandur, Santosh K.; Sharma, Deepak; Checker, Rahul; Agarwal, Beamon; Jha, Dhruv; Majumdar, Anuradha; Gota, Vikram

doi:10.1016/j.intimp.2020.106575

Cited by 9 publications

(4 citation statements)

References 37 publications

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“…Earlier, we established the inhibition of lymphocyte proliferation and cytokine secretion from mouse lymphocytes treated ex vivo with withaferin-A (WA), a principle component of WSE 22 . Next, we established that ex vivo graft manipulation with WA could prevent aGvHD 23 . Furthermore, to bring WA one-step closure to clinic, we established safety, pharmacokinetics and anti-GvHD efficacy of oral WA 13 , 24 .…”

Section: Discussionmentioning

confidence: 99%

Withania Somnifera Extract Mitigates Experimental Acute Graft versus Host Disease Without Abrogating Graft Versus Leukemia Effect

Gupta,

Gohil,

Momin

et al. 2024

Cell Transplant

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Acute graft versus host disease (aGvHD) is the major contributor of nonrelapse mortality in alloHSCT. It is associated with an inflammatory immune response manifesting as cytokine storm with ensuing damage to target organs such as liver, gut, and skin. Prevention of aGvHD while retaining the beneficial graft versus leukemia (GvL) effect remains a major challenge. Withania somnifera extract (WSE) is known for its anti-inflammatory, immune-modulatory, and anticancer properties, which are appealing in the context of aGvHD. Herein, we demonstrated that prophylactic and therapeutic use of WSE in experimental model of alloHSCT mitigates aGvHD-associated morbidity and mortality. In the prophylaxis study, a dose of 75 mg/kg of WSE offered greatest protection against death due to aGvHD (hazard ratio [HR] = 0.15 [0.03-0.68], P ≤ .01), whereas 250 mg/kg was most effective for the treatment of aGvHD (HR = 0.16 [0.05-0.5], P ≤ .01). WSE treatment protected liver, gut, and skin from damage by inhibiting cytokine storm and lymphocytic infiltration to aGvHD target organs. In addition, WSE did not compromise the GvL effect, as alloHSCT with or without WSE did not allow the leukemic A20 cells to grow. In fact, WSE showed marginal antileukemic effect in vivo. WSE is currently under clinical investigation for the prevention and treatment of aGvHD.

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Section: Discussionmentioning

confidence: 99%

Withania Somnifera Extract Mitigates Experimental Acute Graft versus Host Disease Without Abrogating Graft Versus Leukemia Effect

Gupta,

Gohil,

Momin

et al. 2024

Cell Transplant

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“…Roots of Ashwagandha are enriched with Withaferin A and widely used for treatment of arthritis, cystic fibrosis, and irritable bowel syndrome (IBS). Withaferin A inhibits NF‐κB, COX‐2, endothelial cell protein C receptor, cytokines, and also moderates oxidative stress (Gambhir et al, 2015; Mehta et al, 2020). Ashwagandha extract improved the blood parameters such as increase hemoglobin concentration, RBCs count, platelet count, and body weight in mice (Ziauddin et al, 1996).…”

Section: Pharmacology Of Different Herbs and Spices Used In Kwath Pre...mentioning

confidence: 99%

Culinary spices and herbs in managing early and long‐COVID‐19 complications: A comprehensive review

Sharma

2023

Phytotherapy Research

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Human race is preparing for the upsurge and aftermath of COVID‐19 pandemic complicated by novel variants, new waves, variable mortality rate, and post‐COVID complications. Despite use of repurposed drugs, symptomatic treatments and licensing of multiple vaccines, the daily number of cases and rate of transmission are significant. Culinary spices and herbs have been historically used in pandemic and non‐pandemic times to reduce respiratory viral burden. Specific food items and culinary spices can boost the levels of protective immunity and also offer therapeutic benefits against impervious bugs via well‐known as well as less‐known but scientifically testable mechanisms. Here, we analyzed the phytochemicals profile of Ayurvedic herbs and inferred from the clinical trials/observational studies to provide a focused and succinct perspective on the relevance of “food‐based” traditional decoction to moderate COVID‐19 disease and long‐COVID via modulation of immunity and reinstatement of homeostasis. We also underscore the druggable targets in pathogenesis of COVID‐19 which are relevant to the ongoing clinical trials using spices and herbs. This information will provide a strong scientific rationale for standardization of the traditional herbs‐based therapies and adopting the use of herbs, spices, and their formulations for reducing SARS‐CoV‐2 transmission, long‐COVID symptoms, and COVID‐19 disease progression.

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“…1 ) [16] . A recent study from our laboratory demonstrated that ex-vivo treatment of donor cells with WA could ameliorate the onset of Graft versus Host Disease (GvHD) in mouse model of allogeneic bone marrow transplantation by modulating Akt-mTOR signaling pathway [17] . Straughn et al, reported the efficacy of WA against SARS-CoV-2 infection, and suggested that WA could also be used for cancer patient with SARS-CoV-2 infection owing to its anticancer as well as anti-viral properties [18] .…”

Section: Introductionmentioning

confidence: 99%

Safety, toxicity and pharmacokinetic assessment of oral Withaferin-A in mice

et al. 2022

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Prevention of acute graft-versus-host-disease by Withaferin a via suppression of AKT/mTOR pathway

Cited by 9 publications

References 37 publications

Withania Somnifera Extract Mitigates Experimental Acute Graft versus Host Disease Without Abrogating Graft Versus Leukemia Effect

Withania Somnifera Extract Mitigates Experimental Acute Graft versus Host Disease Without Abrogating Graft Versus Leukemia Effect

Culinary spices and herbs in managing early and long‐COVID‐19 complications: A comprehensive review

Safety, toxicity and pharmacokinetic assessment of oral Withaferin-A in mice

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