Liu Xiaqing, Li Pinggan, Yang Xiangna, Xie Ting, Xu Hua
Guangzhou University of Chinese Medicine, Guangzhou, 510405, Guangdong, P. R. China.
Department of Traditional Chinese Medicine, Guangzhou Women and Children's Medical Center, Guangzhou, 510620, Guangdong, P. R. China.
Hereditas. 2025 Apr 8;162(1):56. doi: 10.1186/s41065-025-00420-9.
To evaluate the molecular mechanism of modified Danggui Liuhuang Decoction (MDGLHD) in treating central precocious puberty (CPP).
CPP-related genes were obtained from GEO dataset, MalaCard, DisGeNET and GeneCards databases. MDGLHT ingredients and targets were obtained in TCMSP, HERB, and SwissTargetPrediction databases. Protein-protein interaction (PPI) network was constructed and analyzed using STRING database and Cytoscape 3.9.1. Genetic ontological (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed with DAVID and Metascape databases. Molecular docking was performed with PyMoL and AutoDock-Vina software. The GnRH secretion model was established by E2 induction of GT1-7 cells. CCK-8, ELISA and qRT-PCR were used to detect the effects of MDGLHD on gonadotropin-releasing hormone (GnRH) secretion and endocrine signaling receptor gene expression.
318 potential targets of MDGLHD in CPP treatment were screened out. Quercetin, kaempferol, and (S)-Canadine were considered to be the most important active ingredients in MDGLHD. Bioinformatics analysis showed that these targets were associated with response to hormone, JAK-STAT signaling pathway and HIF-1 signaling pathway. Quercetin, kaempferol, and (s)-Canadine had good binding affinity with tumor protein p53 (TP53), estrogen receptor 1(ESR1), Jun proto-oncogene (JUN), MYC proto-oncogene (MYC) and AKT serine/threonine kinase 1 (AKT1). In vitro experiments showed that MDGLHD extract can inhibit GnRH secretion and the expression of neuroendocrine signaling receptor protein gene.
MDGLHD treatment of CPP is achieved through multi-components, multi-targets and multi-pathways, and inhibition of GnRH secretion and neuroendocrine signaling.
评估加味当归六黄汤（MDGLHD）治疗中枢性性早熟（CPP）的分子机制。
从GEO数据集、MalaCard、DisGeNET和GeneCards数据库中获取与CPP相关的基因。在TCMSP、HERB和SwissTargetPrediction数据库中获取MDGLHT的成分和靶点。使用STRING数据库和Cytoscape 3.9.1构建并分析蛋白质-蛋白质相互作用（PPI）网络。使用DAVID和Metascape数据库进行基因本体论（GO）分析和京都基因与基因组百科全书（KEGG）通路富集分析。使用PyMoL和AutoDock-Vina软件进行分子对接。通过E2诱导GT1-7细胞建立GnRH分泌模型。采用CCK-8、ELISA和qRT-PCR检测MDGLHD对促性腺激素释放激素（GnRH）分泌和内分泌信号受体基因表达的影响。
筛选出MDGLHD治疗CPP的318个潜在靶点。槲皮素、山奈酚和（S）-加拿大麻碱被认为是MDGLHD中最重要的活性成分。生物信息学分析表明，这些靶点与激素反应、JAK-STAT信号通路和HIF-1信号通路相关。槲皮素、山奈酚和（S）-加拿大麻碱与肿瘤蛋白p53（TP53）、雌激素受体1（ESR1）、原癌基因Jun（JUN）、原癌基因MYC（MYC）和AKT丝氨酸/苏氨酸激酶1（AKT1）具有良好的结合亲和力。体外实验表明，MDGLHD提取物可抑制GnRH分泌和神经内分泌信号受体蛋白基因的表达。
MDGLHD通过多成分、多靶点、多途径治疗CPP，并抑制GnRH分泌和神经内分泌信号。
