Chen Xiaohong, Zheng Min, Fei Xiaoling, Ma Xiaohui
Department of Pediatrics, Central Hospital of Haining, Haining, China.
Day Surgery Center, Children's Hospital of Wuhan, Wuhan, China.
Transl Pediatr. 2023 Mar 31;12(3):364-374. doi: 10.21037/tp-23-111. Epub 2023 Mar 30.
Traditional Chinese medicine (TCM) believes that central precocious puberty (CPP) is affected by the imbalance of kidney Yin and Yang. Dabuyin pill is a recipe for nourishing Yin and lowering fire. The network pharmacology method was used to analyze the active components, action targets, and molecular pathways of Dabuyin pill in the treatment of CPP.
The main chemical components of Dabuyin pill were obtained from the Integrative database of Traditional Chinese Medicine enhanced by Symptom Mapping (SymMap) database and Traditional Chinese Medicine Systems Pharmacology (TCMSP), and compound targets were retrieved from SymMap and the Encyclopedia of Traditional Chinese Medicine (ETCM). Disease targets were retrieved from the DisGeNET and Gene Expression Omnibus (GEO) databases, and the intersection of compound targets and disease targets was performed to obtain the prediction targets of Dabuyin pill acting on CPP. The key targets enriched by Database for Annotation, Visualization, and Integrated Discovery (DAVID) were then used for Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.
GO analysis showed that the biological functions of Dabuyin pill in the treatment of key targets of CPP mainly involved apoptosis, nitric oxide synthesis, estradiol response, angiogenesis, inflammation, and so on. KEGG pathway analysis was mainly enriched in the tumor necrosis factor (TNF) signaling pathway, phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling pathway, hypoxia-inducible factor-1 (HIF-1) signaling pathway, and apoptosis. Among them, the regulation effect of Dabuyin pill prescription on apoptosis may both act on TP53 and different signaling pathways of apoptosis, thus playing a synergistic role.
Dabuyin pill combined with GnRHa for the prevention and treatment of CPP in girls can effectively intervene CPP, and the effect of Dabuyin pill on sex hormones is one of its protective mechanisms against CPP.
中医认为中枢性性早熟(CPP)受肾阴阳失调影响。大补阴丸是滋阴降火的方剂。采用网络药理学方法分析大补阴丸治疗CPP的活性成分、作用靶点及分子通路。
大补阴丸的主要化学成分从通过症状映射增强的中医综合数据库(SymMap数据库)和中医系统药理学(TCMSP)中获取,化合物靶点从SymMap和《中医大百科全书》(ETCM)中检索。疾病靶点从DisGeNET和基因表达综合数据库(GEO)中检索,并对化合物靶点和疾病靶点进行交集分析,以获得大补阴丸作用于CPP的预测靶点。然后将通过注释、可视化和综合发现数据库(DAVID)富集的关键靶点用于基因本体(GO)功能富集和京都基因与基因组百科全书(KEGG)通路分析。
GO分析表明,大补阴丸治疗CPP关键靶点的生物学功能主要涉及细胞凋亡、一氧化氮合成、雌二醇反应、血管生成、炎症等。KEGG通路分析主要富集在肿瘤坏死因子(TNF)信号通路、磷脂酰肌醇-3激酶/蛋白激酶B(PI3K/Akt)信号通路、缺氧诱导因子-1(HIF-1)信号通路和细胞凋亡。其中,大补阴丸方剂对细胞凋亡的调控作用可能同时作用于TP53和不同的细胞凋亡信号通路,从而发挥协同作用。
大补阴丸联合GnRHa防治女童CPP可有效干预CPP,大补阴丸对性激素的影响是其防治CPP的保护机制之一。