Zhao Wen-Yan, Xiang Qian, Wang Chan, Wu Xiao-Ying, Zhu Ying-Hui, Yang Dan-Yang, Chen Yu-Xun, Xiao Xiao-Lin, Gong Qian-Feng, Yu Huan
School of Pharmacy, Jiangxi University of Chinese Medicine Nanchang 330004, China.
Zhongguo Zhong Yao Za Zhi. 2022 Oct;47(19):5316-5326. doi: 10.19540/j.cnki.cjcmm.20220314.402.
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.
为阐明吴茱萸制黄连水煎剂治疗慢性结肠炎的作用机制，本研究采用超高效液相色谱-四极杆飞行时间质谱联用技术（UPLC-Q-TOF-MS）、网络药理学及实验验证，预测其涉及的靶点和信号通路。构建慢性结肠炎小鼠模型以验证核心靶点。通过UPLC-Q-TOF-MS鉴定出该草药中的48种化合物。利用SwissTargetPrediction筛选潜在活性成分和药物靶点。通过GeneCards、OMIM、PharmGKB和TDD检索疾病靶点。共获得31种活性成分、该草药的453个靶点以及慢性结肠炎的3960个靶点。将草药与慢性结肠炎的共同靶点导入STRING构建蛋白质-蛋白质相互作用（PPI）网络，并使用CytoNCA插件筛选关键靶点。共获得90个关键靶点，关键活性成分包括异鼠李素、槲皮素、柠檬苦素和氧化小檗碱。通过DAVID对关键靶点进行基因本体（GO）注释和京都基因与基因组百科全书（KEGG）通路富集分析。这些靶点主要参与蛋白质磷酸化的正调控、一氧化氮生物合成过程的正调控以及凋亡过程的负调控。该药物可能通过PI3K-Akt、VEGF、HIF-1和TNF信号通路治疗慢性结肠炎。建立慢性结肠炎小鼠模型，然后用吴茱萸制黄连水煎剂进行治疗。实验结果表明，该药物在治疗慢性结肠炎时可减轻结肠病理损伤，显著降低白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α水平，抑制PI3K/Akt通路的激活，并下调VEGFA的表达。
