Guo Xin, Xu Yunyi, Sun Juan, Wang Qianqian, Kong Haibo, Zhong Zixing
Center for Reproductive Medicine, Department of Obstetrics, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, 310014, China.
Department of Obstetrics and Gynecology, The Second School of Clinical Medicine, Zhejiang Chinese Medical University, 310053, China.
Stem Cells Int. 2022 Aug 28;2022:3299091. doi: 10.1155/2022/3299091. eCollection 2022.
To identify the active chemical in Wenshen Huatan Quyu Decotion (WHQD) and to explore its possible network interactions with the polycystic ovary syndrome (PCOS).
The Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform (TCMSP) and the Bioinformatics Analysis Tool for Molecular Mechanisms in Chinese Medicine (BATMAN-TCM) were used to decompose compound formulations, detect active chemicals and their corresponding target genes, and then convert them into UniProt gene symbols. Meanwhile, PCOS-related target genes were collected from GeneCards to construct a protein-protein interaction (PPI) network, which was further analyzed by STRING online database. Gene Ontology (GO) functional analysis was also performed afterwards to construct the component-target gene-disease network to visualize the correlation between WHQD and PCOS. We then performed an in silico molecular docking study to validate the predicted relationships.
WHQD consists of 14 single drugs containing a total of 67 chemical components. 216 genes were predicted as possible targets. 123 of the 216 target genes overlapped with PCOS. GO annotation analysis revealed that 1968 genes were associated with biological processes, 145 with molecular functions, and 71 with cellular components. KEGG analysis revealed 146 pathways involved PPI, and chemical-target gene-disease networks suggest that PGR, AR, ADRB2, IL-6, MAPK1/8, ESR1/2, CHRM3, RXRA, PPARG, BCL2/BAX, GABRA1, and NR3C2 may be key genes for the pharmacological effects of WHQD on PCOS. Molecular docking analysis confirmed that hydrogen bonding was the main interaction between WHQD and its targets.
WHQD exerts its pharmacological effects by improving insulin sensitivity, subfertility, and hormonal imbalance, increasing ovulation rates, which in turn may increase pregnancy rates in patients with significant efficacy.
确定温肾化痰祛瘀方（WHQD）中的活性成分，并探讨其与多囊卵巢综合征（PCOS）可能的网络相互作用。
利用中药系统药理学数据库与分析平台（TCMSP）和中药分子机制生物信息学分析工具（BATMAN-TCM）对复方制剂进行分解，检测活性成分及其相应的靶基因，然后将其转换为UniProt基因符号。同时，从GeneCards收集PCOS相关靶基因，构建蛋白质-蛋白质相互作用（PPI）网络，并通过STRING在线数据库进一步分析。随后进行基因本体（GO）功能分析，构建成分-靶基因-疾病网络，以可视化WHQD与PCOS之间的相关性。然后进行计算机模拟分子对接研究，以验证预测的关系。
WHQD由14味单药组成，共含67种化学成分。预测有216个基因可能为靶点。216个靶基因中有123个与PCOS重叠。GO注释分析显示，1968个基因与生物过程相关，145个与分子功能相关，71个与细胞成分相关。KEGG分析显示146条通路参与PPI，化学-靶基因-疾病网络表明，孕酮受体（PGR）、雄激素受体（AR）、β2肾上腺素能受体（ADRB2）、白细胞介素-6（IL-6）、丝裂原活化蛋白激酶1/8（MAPK1/8）、雌激素受体1/2（ESR1/2）、毒蕈碱型乙酰胆碱受体3（CHRM3）、视黄酸X受体α（RXRA）、过氧化物酶体增殖物激活受体γ（PPARG）、凋亡调节蛋白Bcl-2/Bax（BCL2/BAX）、γ-氨基丁酸A型受体α1（GABRA1）和核受体亚家族3成员C2（NR3C2）可能是WHQD对PCOS药理作用的关键基因。分子对接分析证实，氢键是WHQD与其靶点之间的主要相互作用。
WHQD通过改善胰岛素敏感性、生育力低下和激素失衡，提高排卵率发挥药理作用，进而可能提高患者的妊娠率，疗效显著。
