Yang Xiao, Mao Yi-Ming, Yao Chong, Song Ding-Ming, He Yi-Bo, Shen Wei
The Third Clinical School of Medicine and Rehabilitation School, Zhejiang Chinese Medicine University, Hangzhou, Zhejiang, China.
Department of Thoracic Surgery, Suzhou Kowloon Hospital, Shanghai Jiao Tong University School of Medicine, Suzhou, Jiangsu, China.
Front Pharmacol. 2024 Nov 29;15:1446707. doi: 10.3389/fphar.2024.1446707. eCollection 2024.
Chen's Peiyuan Tang (CSPYT) is a compound herbal formula that has shown the potential to enhance ovarian function and reduce autophagy in ovarian granulosa cells, which plays a crucial role in follicular development and maturation. The application of Chinese herbal medicine offers a promising alternative to traditional hormone replacement therapy (HRT).
This study explores CSPYT's therapeutic mechanisms in treating POF, focusing on its modulation of autophagy through network pharmacology and transcriptomics-based analysis, predicting potential interactions and pathways. KGN cell line and rat ovarian granulosa cells were used for experiment. 4-Hydroperoxy cyclophosphamide(4-HC) stimulation was carried out for establishing the POF cell model. Q-PCR, Western Blot, Transmission electron microscopy to detect the results.
According to the drug and disease database, the common targets of Chen's Peiyuan Tang and premature ovarian failure were screened, combined with autophagy gene targets and transcriptome analysis, and finally 8 intersection targets were obtained, namely CDKN1B, MAPK3, PRKCD, CDKN1A, MAPK1, RAF1, BIRC5, CTSB. Enrichment analysis of 8 genes found that they were closely related to the animal autophagy pathway. Construct PPI network diagram. CytoScape 3.9.1 builds CSPYT Drug Target-POF Disease Target-Autophagy Gene Network Diagram. Based on the PPI network diagram and CytoScape 3.9.1 analysis results, it is estimated that MAPK1 and MAPK3 are the key targets of CSPYT in the treatment of POF. The eight final intersection targets were docked with the corresponding active pharmaceutical ingredients. The one that docked most closely with the MAPK family was naringenin. In cell experiment verification, it was confirmed that Chen's Peiyuan Tang can inhibit the MAPK signaling pathway, significantly reduce the number of autophagosomes, and reduce autophagy damage in ovarian granulosa cells.
CSPYT can inhibit the MAPK signaling pathway, prevent autophagy overexpression and restore ovarian granulosa cell function, effectively alleviating the disease pressure of POF.
陈氏培元汤（CSPYT）是一种复方草药配方，已显示出增强卵巢功能和减少卵巢颗粒细胞自噬的潜力，而卵巢颗粒细胞在卵泡发育和成熟中起关键作用。中药的应用为传统激素替代疗法（HRT）提供了一种有前景的替代方案。
本研究探讨CSPYT治疗卵巢早衰的作用机制，重点通过网络药理学和基于转录组学的分析来研究其对自噬的调节作用，预测潜在的相互作用和途径。使用KGN细胞系和大鼠卵巢颗粒细胞进行实验。通过4-氢过氧化环磷酰胺（4-HC）刺激建立卵巢早衰细胞模型。采用q-PCR、蛋白质免疫印迹法、透射电子显微镜检测结果。
根据药物与疾病数据库，筛选出陈氏培元汤与卵巢早衰的共同靶点，结合自噬基因靶点和转录组分析，最终得到8个交集靶点，即CDKN1B、MAPK3、PRKCD、CDKN1A、MAPK1、RAF1、BIRC5、CTSB。对这8个基因的富集分析发现它们与动物自噬途径密切相关。构建蛋白质-蛋白质相互作用（PPI）网络图。利用CytoScape 3.9.1构建CSPYT药物靶点-卵巢早衰疾病靶点-自噬基因网络图。基于PPI网络图和CytoScape 3.9.1分析结果，推测MAPK1和MAPK3是CSPYT治疗卵巢早衰的关键靶点。将8个最终交集靶点与相应的活性药物成分进行对接。与MAPK家族对接最紧密的是柚皮素。在细胞实验验证中，证实陈氏培元汤可抑制MAPK信号通路，显著减少自噬体数量，并减轻卵巢颗粒细胞的自噬损伤。
CSPYT可抑制MAPK信号通路，防止自噬过度表达并恢复卵巢颗粒细胞功能，有效缓解卵巢早衰的疾病压力。
