Yang Pengdi, Fan Meiling, Chen Ying, Yang Dan, Zhai Lu, Fu Baoyu, Zhang Lili, Wang Yanping, Ma Rui, Sun Liwei
The Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, China.
Obstetrics and Gynecology Center, The Affiliated Hospital, Changchun University of Chinese Medicine, Changchun, China.
Pharm Biol. 2025 Dec;63(1):68-81. doi: 10.1080/13880209.2025.2453699. Epub 2025 Jan 25.
The decline in ovarian reserve is a major concern in female reproductive health, often associated with oxidative stress and mitochondrial dysfunction. Although ginsenoside Rg1 is known to modulate mitophagy, its effectiveness in mitigating ovarian reserve decline remains unclear.
To investigate the role of ginsenoside Rg1 in promoting mitophagy to preserve ovarian reserve.
Ovarian reserve function, reproductive capacity, oxidative stress levels, and mitochondrial function were compared between ginsenoside Rg1-treated and untreated naturally aged female using behavioral, histological, and molecular biological techniques. The protective effects of ginsenoside Rg1 were analyzed in a model of oxidative damage induced by tert-butyl hydroperoxide. Protein expression levels in the PINK1/Parkin pathway were assessed, and molecular docking and PINK1 mutant analyses were conducted to identify potential targets.
Ginsenoside Rg1 significantly mitigated ovarian reserve decline, enhancing offspring quantity and quality, increasing the levels of ecdysteroids, preventing ovarian atrophy, and elevating germline stem cell numbers in aged . Ginsenoside Rg1 improved superoxide dismutase, catalase activity, and gene expression while reducing reactive oxygen species levels. Ginsenoside Rg1 activated the mitophagy pathway by upregulating PINK1, Parkin, and Atg8a and downregulating Ref(2)P. Knockdown of PINK1 in the ovary by RNAi attenuated the protective effects of ginsenoside Rg1. Molecular docking analysis revealed that the ginsenoside Rg1 could bind to the active site of the PINK1 kinase domain.
Ginsenoside Rg1 targets PINK1 to regulate mitophagy, preserving ovarian reserve. These findings suggest the potential of ginsenoside Rg1 as a therapeutic strategy to prevent ovarian reserve decline.
卵巢储备功能下降是女性生殖健康的主要问题，常与氧化应激和线粒体功能障碍有关。虽然人参皂苷Rg1已知可调节线粒体自噬，但其在减轻卵巢储备功能下降方面的有效性仍不清楚。
研究人参皂苷Rg1在促进线粒体自噬以维持卵巢储备中的作用。
采用行为学、组织学和分子生物学技术，比较人参皂苷Rg1处理组和未处理的自然衰老雌性小鼠的卵巢储备功能、生殖能力、氧化应激水平和线粒体功能。在叔丁基过氧化氢诱导的氧化损伤模型中分析人参皂苷Rg1的保护作用。评估PINK1/Parkin通路中的蛋白表达水平，并进行分子对接和PINK1突变分析以确定潜在靶点。
人参皂苷Rg1显著减轻卵巢储备功能下降，提高后代数量和质量，增加蜕皮甾体水平，预防卵巢萎缩，并增加老年小鼠的生殖干细胞数量。人参皂苷Rg1提高超氧化物歧化酶、过氧化氢酶活性和基因表达，同时降低活性氧水平。人参皂苷Rg1通过上调PINK1、Parkin和Atg8a以及下调Ref(2)P激活线粒体自噬通路。RNA干扰敲低卵巢中的PINK1可减弱人参皂苷Rg1的保护作用。分子对接分析表明，人参皂苷Rg1可与PINK1激酶结构域的活性位点结合。
人参皂苷Rg1靶向PINK1调节线粒体自噬，维持卵巢储备。这些发现提示人参皂苷Rg1作为预防卵巢储备功能下降的治疗策略具有潜力。
