Zhang Yiqing, Liu Xialu, Zheng Zitong, Huang Haiqiang, Wang Yurou, Wu Shuqin, Shu Yuan, Yang Yuxin, Zhong Yufei, Liao Pengfei, Wang Yongsong, Pan Zezheng
School of Basic Medical Sciences, Jiangxi Medical College, Nanchang University, No.461 Bayi Road, Donghu District, Nanchang, 330006, Jiangxi Province, People's Republic of China.
Jiangxi KingMed Clinical Laboratory Co, Nanchang, 330006, Jiangxi Province, People's Republic of China.
Sci Rep. 2025 Jan 9;15(1):1493. doi: 10.1038/s41598-024-83484-3.
As one of the essential lignan derivative found in traditional Chinese medicinal herbs, secoisolariciresinol diglucoside (SDG) was proved to promote women's health through its phytoestrogenic properties. Increasingly studies indicated that this compound could be a potential drug capable of preventing estrogen-related diseases. Here, we aimed to investigate whether SDG can counteract cyclophosphamide (CTX) induced premature ovarian insufficiency (POI) and further explore its specific molecular mechanism. In this study, we first validated the therapeutic effect of SDG on POI in a mouse model. Then, the mechanism by which SDG improves POI is predicted through a combination of network and pharmacology, and its authenticity is further confirmed by experimental verification, molecular docking analysis and molecular dynamics simulation. The results showed that SDG significantly alleviated POI by improving ovarian indices and follicle counts while protecting against CTX-induced ovarian damage by modulating the PI3K/Akt signaling pathway in KGN cells. In addition, molecular docking studies confirmed SDG's high affinity for Akt1 and PI3Kγ, pinpointing the precise interaction sites. These results underscore the protective mechanisms of SDG against ovarian damage, highlighting its therapeutic potential. In summary, our study identified that SDG can ameliorate CTX-induced POI with its mechanism of action intricately linked to the modulation of the PI3K/Akt signaling pathway.
作为传统中草药中发现的重要木脂素衍生物之一，开环异落叶松脂素二葡萄糖苷（SDG）因其植物雌激素特性被证明可促进女性健康。越来越多的研究表明，这种化合物可能是一种能够预防雌激素相关疾病的潜在药物。在此，我们旨在研究SDG是否能对抗环磷酰胺（CTX）诱导的卵巢早衰（POI），并进一步探索其具体分子机制。在本研究中，我们首先在小鼠模型中验证了SDG对POI的治疗效果。然后，通过网络药理学相结合的方法预测SDG改善POI的机制，并通过实验验证、分子对接分析和分子动力学模拟进一步证实其真实性。结果表明，SDG通过改善卵巢指数和卵泡数量显著减轻POI，同时通过调节KGN细胞中的PI3K/Akt信号通路预防CTX诱导的卵巢损伤。此外，分子对接研究证实了SDG对Akt1和PI3Kγ具有高亲和力，确定了精确的相互作用位点。这些结果强调了SDG对卵巢损伤的保护机制，突出了其治疗潜力。总之，我们的研究发现SDG可以改善CTX诱导的POI，其作用机制与PI3K/Akt信号通路的调节密切相关。
