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<p>Ashwagandha (<i>Withania somnifera</i>), a traditional Ayurvedic adaptogen, is increasingly investigated in hormone-sensitive malignancies such as breast cancer. Its bioactive constituents, particularly withaferin A, exhibit diverse effects relevant to hormonal regulation, tumor suppression, and systemic balance. This review explores Ashwagandha’s tri-axial roles in hormonal modulation, gut microbiota interaction, and direct anticancer activity across breast cancer subtypes. Preclinical findings show that withaferin A suppresses estrogen receptor alpha (ERα), inhibits STAT3 and NF-κB signaling, induces ROS-mediated apoptosis, and alters epigenetic regulators. In HER2-positive and triple-negative models, it reduces cancer stem cell activity, epithelial-to-mesenchymal transition (EMT), and pro-inflammatory mediators. Ashwagandha also influences the hypothalamic–pituitary–gonadal axis, raising LH, FSH, estrogen, and progesterone, while lowering cortisol and normalizing thyroid function. Immunologically, it enhances CD8⁺ T cell activity, reduces myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), and may synergize with checkpoint inhibitors. Effects on gut microbiota suggest additional roles in estrogen metabolism and inflammatory regulation. Toxicity data indicate high tolerability (LD₅₀ &gt; 2000&#xa0;mg/kg), though rare hepatic and thyroid adverse events occur. Regulatory oversight remains inconsistent, with limited phytochemical standardization. Ashwagandha shows multidimensional promise but requires rigorous, standardized clinical validation.</p> Graphical abstract <p></p>

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The interplay of Ashwagandha with hormonal dynamics and gut microbiota in women with breast cancer: a tri-axial perspective

  • 期刊论文

  • 发表日期：

    2026年5月13日

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  • Rawan R. Kawaf,
  • Ayah M. Alkherat,
  • Yasmin Shareef,
  • Loulia Khalid Jandali,
  • Rand Salamalek,
  • Sarra B. Shakartalla,
  • Sama S. Soliman,
  • Nashwa Ahmed Mohamed,
  • Sameh S. M. Soliman

摘要

Ashwagandha (Withania somnifera), a traditional Ayurvedic adaptogen, is increasingly investigated in hormone-sensitive malignancies such as breast cancer. Its bioactive constituents, particularly withaferin A, exhibit diverse effects relevant to hormonal regulation, tumor suppression, and systemic balance. This review explores Ashwagandha’s tri-axial roles in hormonal modulation, gut microbiota interaction, and direct anticancer activity across breast cancer subtypes. Preclinical findings show that withaferin A suppresses estrogen receptor alpha (ERα), inhibits STAT3 and NF-κB signaling, induces ROS-mediated apoptosis, and alters epigenetic regulators. In HER2-positive and triple-negative models, it reduces cancer stem cell activity, epithelial-to-mesenchymal transition (EMT), and pro-inflammatory mediators. Ashwagandha also influences the hypothalamic–pituitary–gonadal axis, raising LH, FSH, estrogen, and progesterone, while lowering cortisol and normalizing thyroid function. Immunologically, it enhances CD8⁺ T cell activity, reduces myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs), and may synergize with checkpoint inhibitors. Effects on gut microbiota suggest additional roles in estrogen metabolism and inflammatory regulation. Toxicity data indicate high tolerability (LD₅₀ > 2000 mg/kg), though rare hepatic and thyroid adverse events occur. Regulatory oversight remains inconsistent, with limited phytochemical standardization. Ashwagandha shows multidimensional promise but requires rigorous, standardized clinical validation.

Graphical abstract