Xu Yuanbo, Wang Piao, Hu Ting, Ning Ke, Bao Yimin
School of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Curr Issues Mol Biol. 2025 Jan 10;47(1):44. doi: 10.3390/cimb47010044.
Mitochondrial homeostasis is crucial for maintaining cellular energy production and preventing oxidative stress, which is essential for overall cellular function and longevity. Mitochondrial damage and dysfunction often occur concomitantly in myocardial ischemia-reperfusion injury (MIRI). Notoginsenoside R1 (NGR1), a unique saponin from the traditional Chinese medicine Panax notoginseng, has been shown to alleviate MIRI in previous studies, though its precise mechanism remains unclear. This study aimed to elucidate the mechanisms of NGR1 in maintaining mitochondrial homeostasis in hypoxia/reoxygenation (H/R) H9c2 cells. The results showed that NGR1 pretreatment effectively increased cell survival rates post-H/R, reduced lactate dehydrogenase (LDH) leakage, and mitigated cell damage. Further investigation into mitochondria revealed that NGR1 alleviated mitochondrial structural damage, improved mitochondrial membrane permeability transition pore (mPTP) persistence, and prevented mitochondrial membrane potential (Δψm) depolarization. Additionally, NGR1 pretreatment enhanced ATP levels, increased the activity of mitochondrial respiratory chain complexes I-V after H/R, and reduced excessive mitochondrial reactive oxygen species (mitoROS) production, thereby protecting mitochondrial function. Further analysis indicated that NGR1 upregulated the expression of mitochondrial biogenesis-related proteins (PGC-1α, Nrf1, Nrf2) and mitochondrial fusion proteins (Opa1, Mfn1, Mfn2), while downregulating mitochondrial fission proteins (Fis1, Drp1) and reducing mitochondrial autophagy (mitophagy) levels, as well as the expression of mitophagy-related proteins (Pink1, Parkin, BNIP3) post-H/R. Therefore, this study showed that NGR1 can maintain mitochondrial homeostasis by regulating mitophagy, mitochondrial fission-fusion dynamics, and mitochondrial biogenesis, thereby alleviating H9c2 cell H/R injury and protecting cardiomyocytes.
线粒体稳态对于维持细胞能量产生和预防氧化应激至关重要，而氧化应激对于整体细胞功能和寿命至关重要。线粒体损伤和功能障碍常伴随发生于心肌缺血再灌注损伤（MIRI）中。三七皂苷R1（NGR1）是传统中药三七中的一种独特皂苷，先前研究已表明其可减轻MIRI，但其确切机制仍不清楚。本研究旨在阐明NGR1在维持缺氧/复氧（H/R）H9c2细胞线粒体稳态中的机制。结果表明，NGR1预处理有效提高了H/R后细胞存活率，减少了乳酸脱氢酶（LDH）泄漏，并减轻了细胞损伤。对线粒体的进一步研究表明，NGR1减轻了线粒体结构损伤，改善了线粒体膜通透性转换孔（mPTP）的持续性，并防止了线粒体膜电位（Δψm）去极化。此外，NGR1预处理提高了ATP水平，增加了H/R后线粒体呼吸链复合物I-V的活性，并减少了过量线粒体活性氧（mitoROS）的产生，从而保护了线粒体功能。进一步分析表明，NGR1上调了线粒体生物发生相关蛋白（PGC-1α、Nrf1、Nrf2）和线粒体融合蛋白（Opa1、Mfn1、Mfn2）的表达，同时下调了线粒体分裂蛋白（Fis1、Drp1）的表达，并降低了线粒体自噬（mitophagy）水平以及H/R后自噬相关蛋白（Pink1、Parkin、BNIP3）的表达。因此，本研究表明，NGR1可通过调节线粒体自噬、线粒体分裂-融合动力学和线粒体生物发生来维持线粒体稳态，从而减轻H9c2细胞H/R损伤并保护心肌细胞。
