Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
J Ethnopharmacol. 2022 Oct 28;297:115540. doi: 10.1016/j.jep.2022.115540. Epub 2022 Jul 20.
Guizhi Fuling decoction (GZFL decoction) is a famous formula in the Synopsis of the Golden Chamber, which has a long history in treating endometriosis. However, its exact mechanism remains unclear.
This study aims to explore the mechanism of GZFL decoction in treating endometriosis, especially in alleviating endometriosis-associated pain.
A combination of system pharmacology and pharmacodynamics was used to explore the specific mechanism of GZFL decoction in the treatment of endometriosis-associated pain. First, the TCMSP database was used to search the components of the GZFL decoction; the parameter index was set as oral bioavailability (OB) ≥ 30% and drug-likeness (DL) ≥ 0.18, while the active ingredients of the drug were screened out. The disease targets of endometriosis were obtained from the TTD, OMIM, Genecards, and DisGeNET databases; the keyword was "endometriosis pain". Network construction and analysis were performed using Cytoscape 3.7.2 software; the David database was used to enrich and analyze the pathways for alleviating endometriosis pain after GZFL decoction treatment. In addition, the network results were verified using experimental animal and cell research.
The results showed the following targets: 76 for the effective chemical components in the prescription, 1329 for disease pain, and 278 for the intersection of drugs and endometriosis pain. The enrichment results for these targets showed that the TNF-PI3K/Akt pathway exhibited research significance. In endometriosis rat models, the GZFL decoction reduced the volume of lesions and relieved pain symptoms. It also reduced the serum levels of IL-6, IL-1β, and TNF-α as well as their expression in the lesion tissues. The GZFL decoction also suppressed the activation of PI3K/Akt downstream signaling proteins.
GZFL decoction could reduce the volume of lesions, suppress inflammation, and decrease the sensitivity to pain in endometriosis rat models through inhibiting PI3K/Akt pathway. This study provides a possible target for traditional Chinese medicine in treating endometriosis-associated pain.
桂枝茯苓汤（GZFL 汤）是《金匮要略》中的著名方剂，在治疗子宫内膜异位症方面历史悠久。然而，其确切机制仍不清楚。
本研究旨在探讨 GZFL 汤治疗子宫内膜异位症，特别是缓解子宫内膜异位症相关疼痛的机制。
采用系统药理学和药效学相结合的方法，探讨 GZFL 汤治疗子宫内膜异位症相关疼痛的具体机制。首先，利用 TCMSP 数据库搜索 GZFL 汤的成分；参数指标设定为口服生物利用度（OB）≥30%和药物相似性（DL）≥0.18，筛选出药物的活性成分。从 TTD、OMIM、Genecards 和 DisGeNET 数据库中获得子宫内膜异位症的疾病靶点；关键词为“子宫内膜异位症疼痛”。使用 Cytoscape 3.7.2 软件进行网络构建和分析；使用 David 数据库对 GZFL 汤治疗后缓解子宫内膜异位症疼痛的途径进行富集和分析。此外，使用实验动物和细胞研究验证网络结果。
结果显示，该处方的有效化学成分有 76 个，疾病疼痛靶点 1329 个，药物与子宫内膜异位症疼痛的交集靶点 278 个。这些靶点的富集结果表明，TNF-PI3K/Akt 通路具有研究意义。在子宫内膜异位症大鼠模型中，GZFL 汤减少了病变体积并缓解了疼痛症状。它还降低了血清中 IL-6、IL-1β 和 TNF-α 的水平及其在病变组织中的表达。GZFL 汤还抑制了 PI3K/Akt 下游信号蛋白的激活。
GZFL 汤通过抑制 PI3K/Akt 通路，可减少子宫内膜异位症大鼠模型的病变体积，抑制炎症反应，降低疼痛敏感性。本研究为中药治疗子宫内膜异位症相关疼痛提供了一个可能的靶点。
