Shi Yaxin, Zhang Chengyuan, Wang Xin, Wang Zilu, Zhang Yiran, Liu Zhiyong, Wang Xin, Shi Wei
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan 250355, China.
Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Evid Based Complement Alternat Med. 2022 Aug 26;2022:6350257. doi: 10.1155/2022/6350257. eCollection 2022.
The effect of GuizhiFuling Wan (GFW) on adenomyosis (AM) is definite. This study aimed to explore the mechanism and key therapeutic targets of GFW in treating AM through network pharmacology combined with molecular docking and experimental verification.
In network pharmacology, firstly, the active components of GFW, its drug, and disease targets were screened through several related public databases, and GFW-AM common targets were obtained after the intersection. Then, the biological function (Gene Ontology, GO) and pathway (Kyoto Encyclopedia of Genes and Genomes, KEGG) of GFW in treating AM were enriched and analyzed. Finally, the interaction and binding force between key components and key targets of GFW were verified by molecular docking. In the animal part, the effect of GFW on the expression of matrix metallopeptidase 2 (MMP-2), matrix metallopeptidase 9 (MMP-9), and vascular endothelial growth factor (VEGF) in mice with AM was observed by HE staining, ELISA, and immunohistochemistry.
In this study, 89 active components of GFW, 102 related targets, and 291 targets of AM were collected. After the intersection, 26 common targets were finally obtained. The key active compounds were baicalein, sitosterol, and -sitosterol, and the key targets were MMP-2, MMP-9, and VEGF. GO and KEGG enrichment analyses showed that biological processes such as the positive regulation of vascular endothelial migration and signaling pathways such as TNF and HIF-1 were involved in regulating angiogenesis, invasion, and metastasis in AM. The molecular docking results showed that baicalein, -sitosterol, and stigmasterol had better binding potential with MMP-2, MMP-9, and VEGF. The results of in vivo analysis showed that GFW could decrease the serum content and protein expression of MMP-2, MMP-9, and VEGF in mice with AM.
GFW could reduce the expression of MMP-2, MMP-9, and VEGF, which might be an essential mechanism for GFW to inhibit the invasion and metastasis of ectopic tissues of AM.
桂枝茯苓丸（GFW）对子宫腺肌病（AM）的疗效确切。本研究旨在通过网络药理学结合分子对接和实验验证，探讨GFW治疗AM的作用机制及关键治疗靶点。
在网络药理学中，首先通过多个相关公共数据库筛选GFW的活性成分、药物靶点和疾病靶点，交集后得到GFW-AM共同靶点。然后，对GFW治疗AM的生物学功能（基因本体论，GO）和通路（京都基因与基因组百科全书，KEGG）进行富集和分析。最后，通过分子对接验证GFW关键成分与关键靶点之间的相互作用和结合力。在动物实验部分，通过苏木精-伊红（HE）染色、酶联免疫吸附测定（ELISA）和免疫组织化学观察GFW对AM小鼠基质金属蛋白酶2（MMP-2）、基质金属蛋白酶9（MMP-9）和血管内皮生长因子（VEGF）表达的影响。
本研究收集了GFW的89种活性成分、102个相关靶点和AM的291个靶点。交集后最终得到26个共同靶点。关键活性化合物为黄芩素、甾醇和β-甾醇，关键靶点为MMP-2、MMP-9和VEGF。GO和KEGG富集分析表明，血管内皮迁移的正调控等生物学过程以及肿瘤坏死因子（TNF）和低氧诱导因子-1（HIF-1）等信号通路参与调节AM中的血管生成、侵袭和转移。分子对接结果表明，黄芩素、β-甾醇和豆甾醇与MMP-2、MMP-9和VEGF具有较好的结合潜力。体内分析结果表明，GFW可降低AM小鼠血清中MMP-2、MMP-9和VEGF的含量及蛋白表达。
GFW可降低MMP-2、MMP-9和VEGF的表达，这可能是GFW抑制AM异位组织侵袭和转移的重要机制。
