State Key Laboratory of Southwestern Chinese Medicine Resources, 611137, Chengdu, China; College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China; School of Public Health, Chengdu University of Traditional Chinese Medicine, 611137, Chengdu, China.
School of Public Health, Chengdu University of Traditional Chinese Medicine, 611137, Chengdu, China.
J Ethnopharmacol. 2023 Oct 28;315:116639. doi: 10.1016/j.jep.2023.116639. Epub 2023 May 16.
Safflower is a traditional Chinese medicine used for treating gynaecological diseases. However, its material basis and mechanism of action in the treatment of endometritis induced by incomplete abortion are still unclear.
This study aimed to reveal the material basis and mechanism of action of safflower in the treatment of endometritis induced by incomplete abortion through comprehensive methods, including network pharmacology and 16S rDNA sequencing.
Network pharmacology and molecular docking methods were used to screen the main active components and potential mechanisms of action of safflower in the treatment of endometritis induced by incomplete abortion in rats. A rat model of endometrial inflammation by incomplete abortion was established. The rats were treated with safflower total flavonoids (STF) based on forecasting results, serum levels of inflammatory cytokines were analysed, and immunohistochemistry, Western blots, and 16S rDNA sequencing were performed to investigate the effects of the active ingredient and the treatment mechanism.
The network pharmacology prediction results showed 20 active components with 260 targets in safflower, 1007 targets related to endometritis caused by incomplete abortion, and 114 drug-disease intersecting targets, including TNF, IL6, TP53, AKT1, JUN, VEGFA, CASP3 and other core targets, PI3K/AKT, MAPK and other signalling pathways may be closely related to incomplete abortion leading to endometritis. The animal experiment results showed that STF could significantly repair uterine damage and reduce the amount of bleeding. Compared with the model group, STF significantly down-regulated the levels of pro-inflammatory factors (IL-6, IL-1β, NO, TNF-α) and the expression of JNK, ASK1, Bax, caspase3, and caspase11 proteins. At the same time, the levels of anti-inflammatory factors (TGF-β and PGE2) and the protein expression of ERα, PI3K, AKT, and Bcl2 were up-regulated. Significant differences in the intestinal flora were seen between the normal group and the model group, and the intestinal flora of the rats was closer to the normal group after the administration of STF.
The characteristics of STF used in the treatment of endometritis induced by incomplete abortion were multi-targeted and involved multiple pathways. The mechanism may be related to the activation of the ERα/PI3K/AKT signalling pathway by regulating the composition and ratio of the gut microbiota.
红花是一种传统的中药，用于治疗妇科疾病。然而，其在治疗不完全性流产引起的子宫内膜炎中的物质基础和作用机制尚不清楚。
本研究旨在通过网络药理学和 16S rDNA 测序等综合方法，揭示红花治疗不完全性流产引起的子宫内膜炎的物质基础和作用机制。
采用网络药理学和分子对接方法筛选红花治疗不完全性流产大鼠子宫内膜炎的主要活性成分及潜在作用机制。建立不完全性流产大鼠子宫内膜炎模型，基于预测结果用红花总黄酮（STF）进行治疗，分析血清中炎症细胞因子水平，采用免疫组织化学、Western blot 和 16S rDNA 测序方法研究活性成分的作用及治疗机制。
网络药理学预测结果显示红花中有 20 个活性成分，260 个靶点，与不完全性流产引起的子宫内膜炎相关的靶点有 1007 个，药物-疾病交集靶点有 114 个，涉及 TNF、IL6、TP53、AKT1、JUN、VEGFA、CASP3 等核心靶点。PI3K/AKT、MAPK 等信号通路可能与不完全性流产导致的子宫内膜炎密切相关。动物实验结果显示，STF 可显著修复子宫损伤，减少出血量。与模型组相比，STF 可显著下调促炎因子（IL-6、IL-1β、NO、TNF-α）和 JNK、ASK1、Bax、caspase3、caspase11 蛋白的表达。同时，上调抗炎因子（TGF-β和 PGE2）和 ERα、PI3K、AKT、Bcl2 蛋白的表达。正常组与模型组比较，肠道菌群有明显差异，STF 给药后，大鼠肠道菌群更接近正常组。
STF 治疗不完全性流产引起的子宫内膜炎的特点是多靶点、多途径。其机制可能与通过调节肠道菌群的组成和比例激活 ERα/PI3K/AKT 信号通路有关。
