Inositol and Berberine Synergistically Reprogram Endocrine and Ovarian Metabolism in Polycystic Ovary Syndrome

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Abstract
Although Myo‐Inositol/D‐Chiro‐Inositol (Ins) and berberine (BBR) have each shown beneficial effects in polycystic ovary syndrome (PCOS), their combined therapeutic potential has not been systematically evaluated. Here, we demonstrate that Ins/BBR exerts superior efficacy compared with single treatments by targeting multiple pathogenic pathways in PCOS. In a DHEA+HFD‐induced mouse model, Ins/BBR restored systemic sex steroid balance, normalized LH/FSH ratio, and improved estrous cyclicity. It also reduced ovarian cysts and enhanced fertility, accompanied by partial normalization of steroidogenic enzyme expression. At the cellular level, Ins/BBR alleviated mitochondrial defects and broadly reprogrammed metabolic landscape in granulosa cells, in specific, restoring nucleotide pools and amino acid turnover and preventing abnormal long‐chain fatty acid accumulation. Together, these findings provide preclinical evidence that Ins/BBR acts through coordinated endocrine, ovarian and metabolic mechanisms, supporting its promise as a safe and effective therapeutic strategy for PCOS.
Funding Information
  • National Natural Science Foundation of China (82495190)
  • National Natural Science Foundation of China (82374225)
  • National Natural Science Foundation of China (82401945)

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