Department of TCM Gynecology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou 310000, PR China; Research Institute of Women's Reproductive Health, Zhejiang Chinese Medical University, Hangzhou 310053, PR China; Zhejiang Key Laboratory of Precise Protection and Promotion of Fertility, Hangzhou 310016, PR China.
Zhejiang Chinese Medical University, Hangzhou, 310053, PR China.
Phytomedicine. 2024 Nov;134:155961. doi: 10.1016/j.phymed.2024.155961. Epub 2024 Aug 17.
The rapid acceleration of female reproductive aging has become a major public health concern. He's Yangchao formula (HSYC), a compound comprising eight herbs, has demonstrated efficacy in enhancing ovarian function. Thus, an in-depth study of its anti-ovarian aging mechanism is required.
To evaluate the anti-ovarian aging effect of HSYC in naturally aged mice and investigate the underlying mechanism by analyzing the gut microbiota (GM), metabolome, and transcriptome.
Young and advanced maternal age (AMA) mice were selected for this study. Hematoxylin and eosin staining, fluorescence staining, western blotting, and qPCR analyses were used to detect the phenotypes associated with ovarian aging. Subsequently, analyses of the GM, transcriptome, and metabolome analyses were performed to explore the potential mechanisms of action of HSYC. Finally, in vivo and in vitro experiments were performed to verify potential therapeutic mechanisms.
HSYC promoted follicular development in AMA mice and ameliorated age-related mitochondrial dysfunction, apoptosis, and defects in DNA damage repair. GM analysis revealed that HSYC treatment significantly increased the abundance of Akkermansia and Turicibacter. Transcriptome and metabolome analyses showed that HSYC might mitigate ovarian aging by regulating metabolic pathways, amino acid metabolism, glutathione metabolism, and the synthesis of pantothenic acid and coenzyme A. Combined transcriptomic and metabolomic analyses identified the glutathione metabolic pathway as the key pathway through which HSYC counteracts ovarian aging. Additional experimental verification confirmed that HSYC upregulated the glutathione metabolic genes GPX8, GSTA1, and GSTA4, increased glutathione-related products (GSH), and reduced ROS levels.
HSYC exerts beneficial therapeutic effects on ovarian aging by regulating multiple endogenous metabolites, targets, and metabolic pathways, with an emphasis on its anti-ovarian aging effects through the glutathione metabolic pathway. These findings underscore the innovative potential of HSYC in addressing ovarian aging and offer a novel therapeutic approach that targets multiple biological pathways to improve the reproductive health of women with AMA..
女性生殖衰老的快速加速已成为一个主要的公共卫生关注问题。和颜坤泰胶囊（HSYC）是一种由八种草药组成的复方制剂，已被证明能增强卵巢功能。因此，需要深入研究其抗卵巢衰老的机制。
评估 HSYC 对自然衰老小鼠的抗卵巢衰老作用，并通过分析肠道微生物群（GM）、代谢组学和转录组学来研究其潜在机制。
本研究选择年轻和高龄（AMA）小鼠。采用苏木精和伊红染色、荧光染色、western blot 和 qPCR 分析检测与卵巢衰老相关的表型。随后，进行 GM、转录组和代谢组学分析，以探讨 HSYC 的潜在作用机制。最后，进行体内和体外实验验证潜在的治疗机制。
HSYC 促进了 AMA 小鼠的卵泡发育，并改善了与年龄相关的线粒体功能障碍、细胞凋亡和 DNA 损伤修复缺陷。GM 分析显示，HSYC 治疗显著增加了 Akkermansia 和 Turicibacter 的丰度。转录组和代谢组学分析表明，HSYC 可能通过调节代谢途径、氨基酸代谢、谷胱甘肽代谢以及泛酸和辅酶 A 的合成来减轻卵巢衰老。综合转录组和代谢组学分析表明，谷胱甘肽代谢途径是 HSYC 对抗卵巢衰老的关键途径。进一步的实验验证证实，HSYC 上调了谷胱甘肽代谢基因 GPX8、GSTA1 和 GSTA4，增加了谷胱甘肽相关产物（GSH），并降低了 ROS 水平。
HSYC 通过调节多种内源性代谢物、靶标和代谢途径对卵巢衰老发挥有益的治疗作用，重点是通过谷胱甘肽代谢途径发挥其抗卵巢衰老作用。这些发现突显了 HSYC 在解决卵巢衰老问题上的创新潜力，并提供了一种新的治疗方法，该方法针对多个生物途径，改善 AMA 女性的生殖健康。
