康妇消炎栓(KFXYS)是临床上治疗慢性盆腔炎(CPID)的常用中药制剂,其安全性和有效性得到了很好的验证。然而,潜在机制尚不清楚.该研究采用代谢组学和网络药理学的整合策略,以揭示KFXYS治疗CPID的潜在机制。我们的研究包括五个步骤。首先,验证了KFXYS逆转子宫炎症指标的作用。第二,基于KFXYS的123种化学成分的综合表征,通过UPLC-Q-TOF/MS鉴定血液中吸收的KFXYS成分,然后对主要成分进行了ADME研究。第三,通过代谢组学和相关性分析发现了与炎症指标显著相关的差异代谢产物。第四,根据具有良好ADME行为的成分,通过网络药理学预测了KFXYS治疗CPID的潜在靶标和途径。第五,代谢组学和网络药理学共同途径中的蛋白质被用来从网络药理学的潜在靶标中筛选关键靶标,阐明了KFXYS治疗CPID的潜在机制。因此,KFXYS显著逆转子宫炎症指标,包括IL-1和IL-6。血液中吸收的成分包括苦参碱,食果芸香碱,芦荟,七叶乙素-O-葡糖苷酸,7,4'-二羟基异黄酮-O-葡糖苷酸,和4'-甲氧基异黄酮-7-O-葡糖苷酸在体内具有良好的ADME行为。在不同的代谢物中,白三烯A4,5-羟基吲哚乙酸,鸟氨酸,精氨酸,和PC(20:1(11Z)/20:4(8Z,11Z,14Z,17Z))与炎症指标显著相关。代谢组学和网络药理学的整合分析表明,KFXYS可能调控ARG1、NOS2、NOS3等关键靶点。我们推测KFXYS的成分,如苦参碱,食果芸香碱,芦荟等.作用于ARG1,NOS2和NOS3等关键蛋白,发挥抗炎作用。
Kangfuxiaoyan suppository (KFXYS) is a commonly used traditional Chinese medicine (TCM) preparation for the treatment of chronic pelvic inflammatory disease (CPID) clinically, and its safety and effectiveness have been well verified. However, the potential mechanism remains unclear. The integrated strategy of metabolomics and network pharmacology was employed in the
study to reveal the potential mechanism of KFXYS in the treatment of CPID. Our research consists of five steps. First, the effect of KFXYS in reversing uterine inflammation indexes was verified. Second, based on the comprehensive characterization of 123 chemical ingredients of KFXYS, the ingredients of KFXYS absorbed into blood were identified by UPLC-Q-TOF/MS, then ADME research was carried out on the main ingredients. Third, the differential metabolites with significant correlation to inflammatory indexes were discovered by metabolomics and correlation analysis. Fourth, the potential targets and pathways of KFXYS in treating CPID were predicted by network pharmacology based on the ingredients which had good ADME behavior. Fifth, the proteins in common pathways of metabolomics and network pharmacology were used to screen the key targets from the potential targets of network pharmacology, and the potential mechanism of KFXYS in treating CPID was clarified. As a result, KFXYS significantly reversed the uterine inflammation indexes, including IL-1 and IL-6. The ingredients absorbed into blood including matrine, sophocarpine, aloin, esculetin-O-glucuronide, 7,4\'-dihydroxyisoflavone-O-glucuronide, and 4\'-methoxyisoflavone-7-O-glucuronide had good ADME behavior in vivo. Among the differential metabolites, Leukotriene A4, 5-Hydroxyindoleacetic acid, Ornithine, Arginine, and PC (20:1 (11Z)/20:4 (8Z,11Z,14Z,17Z)) were significant correlation to inflammation indexes. The integration analysis of metabolomics and network pharmacology shows that KFXYS may regulate the key targets including ARG1, NOS2, NOS3, etc. We speculate that ingredients of KFXYS, such as matrine, sophocarpine, aloin etc. act on the key proteins including ARG1, NOS2, and NOS3, to exert anti-inflammatory effect.