摘要
为阐明樟帮特色炮制品黄连水炒吴茱萸治疗慢性结肠炎的作用机制,该研究采用UPLC-Q-TOF-MS技术、网络药理学和实验验证方法,预测慢性结肠炎的作用靶点和信号通路,并构建慢性结肠炎小鼠模型对核心靶点进行验证。通过UPLC-Q-TOF-MS技术鉴定出48种化合物;利用SwissTargetPrediction数据库筛选,得到潜在活性成分31种及药物靶点453个;在GeneCards、OMIM、PharmGKB、TDD数据库筛选得到3 960个慢性结肠炎相关靶点,将药物靶点与疾病靶点匹配所得交集靶点导入STRING构建蛋白质-蛋白质相互作用(PPI)网络,借助CytoNCA插件筛选出90个关键靶点,筛选出异鼠李素、槲皮素、柠檬苦素、氧化小檗碱等关键成分;利用DAVID数据库对关键靶点进行GO和KEGG富集分析,结果显示靶点主要涉及蛋白质磷酸化的正调节、一氧化氮生物合成过程的正调控、凋亡过程的负调控等生物学过程,通过PI3K-Akt、VEGF、HIF-1、TNF等信号通路发挥治疗慢性结肠炎的作用。构建慢性结肠炎小鼠模型,黄连水炒吴茱萸干预后可改善结肠病理损伤,显著降低白细胞介素(IL)-1β、IL-6和肿瘤坏死因子(TNF)-α水平,抑制PI3K-Akt通路的激活,并降低VEGFA蛋白的表达,从而发挥治疗慢性结肠炎的作用。
To elucidate the mechanism of Euodiae Fructus stir-fried with water decoction of Coptidis Rhizoma in the treatment of chronic colitis, this study employed ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS), network pharmacology, and experimental verification to predict the involved targets and signaling pathways. The chronic colitis mouse model was constructed to verify the core targets. A total of 48 compounds in the herbal medicine were identified by UPLC-Q-TOF-MS. SwissTargetPrediction was used to screen the potential active components and drug targets. GeneCards, OMIM, PharmGKB, and TDD were used to search for the disease targets. A total of 31 active ingredients, 453 targets of the herbal medicine, and 3 960 targets of chronic colitis were obtained. The common targets shared by the herbal medicine and chronic colitis were introduced into STRING to construct the protein-protein interaction(PPI) network, and CytoNCA plug-in was used to screen the key targets. A total of 90 key targets were obtained, and the key active components included isorhamnetin, quercetin, limonin, and oxyberberine. GO annotation and KEGG pathway enrichment for the key targets were carried out via DAVID. The targets were mainly involved in the positive regulation of protein phosphorylation, positive regulation of nitric oxide biosynthetic process, and negative regulation of apoptotic process. The medicine may treat chronic colitis through PI3 K-Akt, VEGF, HIF-1, and TNF signaling pathways. A mouse model of chronic colitis was established and then treated with Euodiae Fructus stir-fried with the water decoction of Coptidis Rhizoma. The experimental results demonstrated that the medicine can alleviate the pathological damage of colon, significantly reduce the levels of IL-1β, IL-6, and TNF-α, inhibit the activation of PI3 K/Akt pathway, and down-regulate the expression of VEGFA in the treatment of chronic colitis.
作者
赵文燕
向茜
王蝉
吴晓莹
朱盈徽
杨丹阳
陈雨迅
肖小林
龚千锋
于欢
ZHAO Wen-yan;XIANG Qian;WANG Chan;WU Xiao-ying;ZHU Ying-hui;YANG Dan-yang;CHEN Yu-xun;XIAO Xiao-lin;CONG Qian-feng;YU Huan(School of Pharmacy,Jiangxi University of Chinese Medicine,Nanchang 330004,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2022年第19期5316-5326,共11页
China Journal of Chinese Materia Medica
基金
国家中医药管理局标准化建设项目(ZYBZH-Y-JX-27)。
