Mangiferin Attenuates Aflatoxin B1-Induced Ferroptosis by Activating of Nrf2-Signaling and Mitochondrial Biogenesis in Human Ovarian Granulosa Cells.

Abstract

Oxidative stress is increasingly recognized as a critical pathogenic factor in ovarian granulosa cell dysfunction and the progression of female reproductive disorders. Accumulating evidence suggests that environmental toxicants contribute to ovarian pathogenesis. For example, aflatoxin B1 (AFB1), a widespread foodborne mycotoxin, is a potent inducer of oxidative stress. After metabolic activation, AFB1 generates reactive oxygen species, causing lipid, protein, and mitochondrial dysfunction. AFB1 also triggers ferroptotic cell death through iron accumulation, glutathione peroxidase 4 downregulation, and lipid peroxidation. Mangiferin (MA), a natural polyphenolic compound with potent antioxidant and cytoprotective effects, has been reported to modulate redox-sensitive signaling pathways. However, whether MA protects human ovarian granulosa cells against oxidative stress and ferroptotic cascades induced by AFB1 exposure remains unclear. In this study, we examined the mechanisms by which MA attenuates AFB1-induced oxidative stress and ferroptosis in granulosa cells through the activation of Nrf2 signaling and mitochondrial biogenesis. These findings highlight the potential of MA as a nutraceutical candidate for alleviating AFB1-induced granulosa cell toxicity.

Key Findings

• Aflatoxin B1 (AFB1) induces oxidative stress and ferroptotic cell death in human ovarian granulosa cells via iron accumulation, glutathione peroxidase 4 downregulation, and lipid peroxidation.
• Mangiferin (MA) attenuates AFB1-induced oxidative stress and ferroptosis by activating Nrf2 signaling and promoting mitochondrial biogenesis.
• MA exhibits potent antioxidant and cytoprotective effects that mitigate granulosa cell toxicity caused by AFB1 exposure.

Clinical Significance

Citation

Ruan Chi-Wai, Tsai Hsin-Yi, Hung Chih-Hsinet al.. Mangiferin Attenuates Aflatoxin B1-Induced Ferroptosis by Activating of Nrf2-Signaling and Mitochondrial Biogenesis in Human Ovarian Granulosa Cells. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2026-Jul-10.