中草药单体调节氧化磷酸化干预DKD的分子机制
Molecular Mechanisms of Monomer Compounds from Chinese Herbal Medicine in Regulating Oxidative Phosphorylation for Intervention in Diabetic Kidney Disease
摘要: 糖尿病肾病(DKD)的病理进展与线粒体氧化磷酸化(OXPHOS)功能障碍以及氧化应激密切相关，但目前缺乏直接靶向该通路的有效治疗药物。本研究系统性地评估了多种中药单体调节线粒体OXPHOS通路、缓解氧化应激的分子机制及其临床转化潜力。我们发现，不同类型的中药单体通过靶向调控线粒体电子传递链(ETC)的特定复合物来发挥肾脏保护作用。例如，多酚类化合物主要激活SIRT1/PGC-1α信号轴，增强氧化磷酸化活性；苷类化合物通过Nrf2/TFAM通路促进线粒体生物合成并恢复氧化磷酸化。这些发现揭示了不同类型中药单体在多层次、多靶点调控线粒体OXPHOS系统中的巨大潜力，为开发新型DKD治疗药物提供了坚实的理论框架和多靶点选择。
Abstract: The pathological progression of diabetic kidney disease (DKD) is closely associated with mitochondrial oxidative phosphorylation (OXPHOS) dysfunction and oxidative stress, yet effective therapeutic agents directly targeting this pathway remain scarce. This study systematically evaluated the molecular mechanisms by which multiple Chinese herbal monomers modulate the mitochondrial OXPHOS pathway and alleviate oxidative stress, alongside their clinical translational potential. We discovered that distinct classes of TCM monomers exert renal protective effects by targeting specific complexes within the mitochondrial electron transport chain (ETC). For instance, polyphenolic compounds primarily activate the SIRT1/PGC-1α signaling axis to enhance oxidative phosphorylation activity, whilst glycosides promote mitochondrial biogenesis and restore oxidative phosphorylation via the Nrf2/TFAM pathway. These findings reveal the substantial potential of diverse TCM monomers to regulate the mitochondrial OXPHOS system through multi-level, multi-target mechanisms, providing a robust theoretical framework and multi-target options for developing novel DKD therapeutics.
文章引用：尹程倩, 王立范. 中草药单体调节氧化磷酸化干预DKD的分子机制[J]. 中医学, 2025, 14(12): 5389-5398. https://doi.org/10.12677/tcm.2025.1412775

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