Abstract：
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：红花是一种用于治疗妇科疾病的中药。然而,其治疗不完全流产子宫内膜炎的物质基础和作用机制尚不清楚。
目的：本研究旨在通过综合方法揭示红花治疗不完全流产子宫内膜炎的物质基础和作用机制。包括网络药理学和16SrDNA测序。
方法：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和潜在作用机制。建立不完全流产子宫内膜炎症大鼠模型。根据预测结果用红花总黄酮(STF)处理大鼠,血清炎性细胞因子水平进行了分析，和免疫组织化学，西方印迹,进行16SrDNA测序以研究活性成分的作用和治疗机理。
结果：网络药理学预测结果显示红花中的20种活性成分和260种靶标，1007个与不完全流产引起的子宫内膜炎相关的目标，和114个药物-疾病交叉目标，包括TNF,IL6,TP53,AKT1,JUN,VEGFA,CASP3和其他核心目标，PI3K/AKT,MAPK和其他信号通路可能与导致子宫内膜炎的不完全流产密切相关。动物实验结果表明，STF能显著修复子宫损伤，减少出血量。与模型组相比，STF显著下调促炎因子(IL-6、IL-1β、NO,TNF-α)和JNK的表达，ASK1,Bax,caspase3和caspase11蛋白。同时,抗炎因子(TGF-β和PGE2)水平和ERα蛋白表达,PI3K,AKT,和Bcl2上调。正常组与模型组肠道菌群差异显著,给予STF后，大鼠肠道菌群更接近正常组。
结论：STF治疗不完全流产子宫内膜炎具有多靶点、多途径的特点。该机制可能与通过调节肠道微生物群的组成和比例激活ERα/PI3K/AKT信号通路有关。
目的：本研究旨在通过综合方法揭示红花治疗不完全流产子宫内膜炎的物质基础和作用机制。包括网络药理学和16SrDNA测序。
方法：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和潜在作用机制。建立不完全流产子宫内膜炎症大鼠模型。根据预测结果用红花总黄酮(STF)处理大鼠,血清炎性细胞因子水平进行了分析，和免疫组织化学，西方印迹,进行16SrDNA测序以研究活性成分的作用和治疗机理。
结果：网络药理学预测结果显示红花中的20种活性成分和260种靶标，1007个与不完全流产引起的子宫内膜炎相关的目标，和114个药物-疾病交叉目标，包括TNF,IL6,TP53,AKT1,JUN,VEGFA,CASP3和其他核心目标，PI3K/AKT,MAPK和其他信号通路可能与导致子宫内膜炎的不完全流产密切相关。动物实验结果表明，STF能显著修复子宫损伤，减少出血量。与模型组相比，STF显著下调促炎因子(IL-6、IL-1β、NO,TNF-α)和JNK的表达，ASK1,Bax,caspase3和caspase11蛋白。同时,抗炎因子(TGF-β和PGE2)水平和ERα蛋白表达,PI3K,AKT,和Bcl2上调。正常组与模型组肠道菌群差异显著,给予STF后，大鼠肠道菌群更接近正常组。
结论：STF治疗不完全流产子宫内膜炎具有多靶点、多途径的特点。该机制可能与通过调节肠道微生物群的组成和比例激活ERα/PI3K/AKT信号通路有关。
