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<p><i>Withania somnifera</i> (Ashwagandha), a member of the Solanaceae family, produces bioactive metabolites known as withanolides, predominantly synthesized in its leaves and roots. Among these, Withaferin-A is a major pharmacologically active compound with demonstrated efficacy across diverse preclinical models. It exhibits anti-cancer, anti-diabetic, anti-viral (including COVID-19), and neuroprotective activities through modulation of oncoproteins and cell signalling pathways. Notably, its specificity toward tumour-associated antigens and immune regulators positions Withaferin-A as a potential alternative to conventional therapies such as chemotherapy and radiotherapy, which often present severe side effects and resistance issues. This review critically explores the biosynthetic routes of Withaferin-A, encompassing chemical synthesis, natural extraction, and microbial production, while also emphasizing strategies for yield optimization through biotechnological interventions. Furthermore, we discuss the bioavailability and pharmacokinetic challenges of Withaferin-A, highlighting formulation and delivery strategies aimed at enhancing its clinical applicability. Overall, the review outlines its translational potential and provides a roadmap for future therapeutic and clinical integration.</p>

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Harnessing microbial factories for withaferin-a: the future of plant-based oncotherapeutics

  • 期刊论文

  • 发表日期：

    2025年11月22日

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  • Naimi Sirjohn,
  • Gaurav Sharma,
  • Duni Chand,
  • Kwon-Young Choi,
  • Pryanka Thakur,
  • Vikram Thakur,
  • Mahender Singh Thakur,
  • Sourabh Kulshreshtha,
  • Sanjay K. S. Patel,
  • Pradeep Kumar

摘要

Withania somnifera (Ashwagandha), a member of the Solanaceae family, produces bioactive metabolites known as withanolides, predominantly synthesized in its leaves and roots. Among these, Withaferin-A is a major pharmacologically active compound with demonstrated efficacy across diverse preclinical models. It exhibits anti-cancer, anti-diabetic, anti-viral (including COVID-19), and neuroprotective activities through modulation of oncoproteins and cell signalling pathways. Notably, its specificity toward tumour-associated antigens and immune regulators positions Withaferin-A as a potential alternative to conventional therapies such as chemotherapy and radiotherapy, which often present severe side effects and resistance issues. This review critically explores the biosynthetic routes of Withaferin-A, encompassing chemical synthesis, natural extraction, and microbial production, while also emphasizing strategies for yield optimization through biotechnological interventions. Furthermore, we discuss the bioavailability and pharmacokinetic challenges of Withaferin-A, highlighting formulation and delivery strategies aimed at enhancing its clinical applicability. Overall, the review outlines its translational potential and provides a roadmap for future therapeutic and clinical integration.