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<p>Polycystic ovary syndrome with insulin resistance (PCOS-IR) features oxidative stress, chronic inflammation, and lipid dysregulation that impair granulosa cells. This study evaluated whether Rhein mitigates oxidative/inflammatory injury in granulosa cells under PCOS-like conditions and explored its putative molecular basis. A PCOS-like metabolic injury model was established in human granulosa-like KGN cells using dihydrotestosterone, oleic acid, and palmitic acid. Reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential (ΔΨm), and lipid accumulation were measured by DCFH-DA fluorescence, MDA assay, JC-1 staining, and Oil Red O, respectively. Western blotting assessed NF-κB, TNF-α, IL-6, and PTGS2. Network pharmacology, molecular docking, 100-ns molecular dynamics simulations were used to prioritize targets and evaluate binding stability. KEGG enrichment was used to infer related pathways. Rhein (10–20&#xa0;μM) reduced ROS and MDA, partially restored ΔΨm, and lessened lipid accumulation versus model controls. Docking and MD results indicated stable binding of Rhein to NF-κB, TNF-α, IL-6, and PTGS2. Enrichment analysis suggested that the NF-κB-TNF-α/IL-6/PTGS2 inflammatory axis may constitute the core regulatory axis. Western blotting further confirmed downregulation of PTGS2, IL-6, TNF-α, and NF-κB protein expression. Rhein attenuates oxidative and inflammatory stress in KGN cells under PCOS-like metabolic injury, likely via modulation of the NF-κB-TNF-α/IL-6/PTGS2 inflammatory axis. These in vitro findings support Rhein as a pharmacological candidate for further investigation in reproductive endocrine disorders associated with insulin resistance.</p>

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Rhein attenuates oxidative stress-induced injury in human ovarian granulosa cells by inhibiting the NF-κB-TNF-α/IL-6/PTGS2 inflammatory axis

  • 期刊论文

  • 发表日期：

    2025年12月22日

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  • Yang Li,
  • Jishuang Qiu,
  • Yanru Zhou,
  • Yuanyuan Jiang,
  • Xin Li,
  • Ying Weng,
  • Yang Chen,
  • Yong Lai,
  • Wanqi Yang

摘要

Polycystic ovary syndrome with insulin resistance (PCOS-IR) features oxidative stress, chronic inflammation, and lipid dysregulation that impair granulosa cells. This study evaluated whether Rhein mitigates oxidative/inflammatory injury in granulosa cells under PCOS-like conditions and explored its putative molecular basis. A PCOS-like metabolic injury model was established in human granulosa-like KGN cells using dihydrotestosterone, oleic acid, and palmitic acid. Reactive oxygen species (ROS), malondialdehyde (MDA), mitochondrial membrane potential (ΔΨm), and lipid accumulation were measured by DCFH-DA fluorescence, MDA assay, JC-1 staining, and Oil Red O, respectively. Western blotting assessed NF-κB, TNF-α, IL-6, and PTGS2. Network pharmacology, molecular docking, 100-ns molecular dynamics simulations were used to prioritize targets and evaluate binding stability. KEGG enrichment was used to infer related pathways. Rhein (10–20 μM) reduced ROS and MDA, partially restored ΔΨm, and lessened lipid accumulation versus model controls. Docking and MD results indicated stable binding of Rhein to NF-κB, TNF-α, IL-6, and PTGS2. Enrichment analysis suggested that the NF-κB-TNF-α/IL-6/PTGS2 inflammatory axis may constitute the core regulatory axis. Western blotting further confirmed downregulation of PTGS2, IL-6, TNF-α, and NF-κB protein expression. Rhein attenuates oxidative and inflammatory stress in KGN cells under PCOS-like metabolic injury, likely via modulation of the NF-κB-TNF-α/IL-6/PTGS2 inflammatory axis. These in vitro findings support Rhein as a pharmacological candidate for further investigation in reproductive endocrine disorders associated with insulin resistance.