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女贞子和墨旱莲中的女贞苷和墨旱莲皂苷A通过作用于雌激素受体1(ESR1)改善卵巢早衰。

Specnuezhenide and ecliptasaponin A from Ligustrum lucidum Ait and Ecliptae Herba improved premature ovarian failure by targeting the ESR1.

作者信息

Xu Jia, Lei Lei, Li Ping, Huang Zi-Chun, Meng Ying, He Bing, Kuang Ji-Lin

机构信息

Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, 410005, PR China.

College of Integrated Traditional Chinese and Western Medicine, Hunan University of Chinese Medicine, Changsha, 410208, PR China.

出版信息

J Pharmacol Sci. 2025 May;158(1):13-26. doi: 10.1016/j.jphs.2025.02.011. Epub 2025 Feb 28.

DOI:10.1016/j.jphs.2025.02.011
PMID:40121053
Abstract

This study was designed to investigate the role of Ligustrum lucidum Ait and Ecliptae Herba on premature ovarian failure (POF) and the underlying mechanisms. In the POF mouse model constructed using cyclophosphamide (CTX), Ligustrum lucidum Ait and Ecliptae Herba increased ovarian index and estradiol (E2) levels and curtailed motility and follicle-stimulating hormone (FSH). Ligustrum lucidum Ait and Ecliptae Herba alleviated ovarian pathological damage in POF mice and promoted the expression of ovarian CD31 and Vascular Endothelial Growth Factor A (VEGFA). Through high-performance liquid chromatography-mass spectrometry (HPLC-MS) and network pharmacology, Specnuezhenide and ecliptasaponin A were identified as the key components of Ligustrum lucidum Ait and Ecliptae Herba in anti-POF action. The important target associated with these components is Estrogen Receptor (ESR) 1. Molecular docking and in vitro experiments showed that Specnuezhenide and ecliptasaponin A can both bind to the ESR protein; knocking down ESR1 inhibited the anti-apoptotic effect of Specnuezhenide and ecliptasaponin A on CTX-induced POF cells. In conclusion, the key components of Ligustrum lucidum Ait and Ecliptae Herba that alleviate POF are Specnuezhenide and ecliptasaponin A, which improve the condition by upregulating ESR1.

摘要

本研究旨在探讨女贞子和墨旱莲对卵巢早衰(POF)的作用及其潜在机制。在使用环磷酰胺(CTX)构建的POF小鼠模型中,女贞子和墨旱莲增加了卵巢指数和雌二醇(E2)水平,并降低了动情和卵泡刺激素(FSH)水平。女贞子和墨旱莲减轻了POF小鼠的卵巢病理损伤,并促进了卵巢CD31和血管内皮生长因子A(VEGFA)的表达。通过高效液相色谱-质谱联用(HPLC-MS)和网络药理学,鉴定出特女贞苷和墨旱莲皂苷A为女贞子和墨旱莲抗POF作用的关键成分。与这些成分相关的重要靶点是雌激素受体(ESR)1。分子对接和体外实验表明,特女贞苷和墨旱莲皂苷A均可与ESR蛋白结合;敲低ESR1可抑制特女贞苷和墨旱莲皂苷A对CTX诱导的POF细胞的抗凋亡作用。总之,女贞子和墨旱莲减轻POF的关键成分是特女贞苷和墨旱莲皂苷A,它们通过上调ESR1来改善病情。

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