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黄芪治疗溃疡性结肠炎疗效机制的系统研究。

Systemic investigation of the mechanism underlying the therapeutic effect of Astragalus membranaceus in ulcerative colitis.

作者信息

Mao Jingxin, Tan Lihong, Tian Cheng, Wang Wenxiang, Zou YanLin, Zhu Zhaojing, Li Yan

机构信息

Department of Science and Technology Industry, Chongqing Medical and Pharmaceutical College, Chongqing 400030, China; College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, China.

Department of Science and Technology Industry, Chongqing Medical and Pharmaceutical College, Chongqing 400030, China; Chongqing Key Laboratory of High Active Traditional Chinese Drug Delivery System, Chongqing Medical and Pharmaceutical College, Chongqing 400030, China.

出版信息

Am J Med Sci. 2025 Feb;369(2):238-251. doi: 10.1016/j.amjms.2024.07.019. Epub 2024 Jul 14.

Abstract

BACKGROUND

Whether Astragalus membranaceus is an effective drug in the treatment of ulcerative colitis (UC) is unknown and how it exhibits activity in UC is unclear.

METHODS

TCMSP, GeneCards, String, and DAVID databases were used to screen target genes in PPI network and we performed GO and KEGG pathway enrichment analysis. Molecular docking and animal experiments were performed. The body weight and disease activity index (DAI) of mice were recorded. ELISA kits were used to detect the levels of CAT, SOD, MDA and IL-6, IL-10, TNF-α in the blood of mice. Western blot kits were utilized to measure the expression of MAPK14, RB1, MAPK1, JUN, ATK1, and IL2 proteins.

RESULTS

The active components of Astragalus membranaceus mainly include 7-O-methylisomucronulatol, quercetin, kaempferol, formononetin and isrhamnetin. Astragalus membranaceus may inhibit the expression of TNF-α, IL-6, MDA, while promoting the expression of CAT, SOD, and IL-10. The expression levels of MAPK14, RB1, MAPK1, JUN and ATK1 proteins were significantly decreased while IL2 protein increased after administration of Astragalus membranaceus.

CONCLUSIONS

Astragalus membranaceus may be an effective drug in the treatment of UC by acting on targets with anti-UC effect via its antioxidant action and by regulating the balance of pro-inflammatory and anti-inflammatory factors.

摘要

背景

黄芪是否为治疗溃疡性结肠炎(UC)的有效药物尚不清楚,其在UC中发挥作用的机制也不明确。

方法

利用中药系统药理学数据库与分析平台(TCMSP)、基因卡片(GeneCards)、搜索工具检索相互作用基因(String)和数据库注释、可视化与综合发现(DAVID)数据库筛选蛋白质-蛋白质相互作用(PPI)网络中的靶基因,并进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。进行分子对接和动物实验。记录小鼠体重和疾病活动指数(DAI)。使用酶联免疫吸附测定(ELISA)试剂盒检测小鼠血液中过氧化氢酶(CAT)、超氧化物歧化酶(SOD)、丙二醛(MDA)以及白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)的水平。利用蛋白质免疫印迹(Western blot)试剂盒检测丝裂原活化蛋白激酶14(MAPK14)、视网膜母细胞瘤蛋白1(RB1)、丝裂原活化蛋白激酶1(MAPK1)、原癌基因蛋白c-Jun(JUN)、蛋白激酶B1(ATK1)和白细胞介素2(IL2)蛋白的表达。

结果

黄芪的活性成分主要包括7-O-甲基异微柔毛醇、槲皮素、山奈酚、芒柄花素和异鼠李素。黄芪可能抑制TNF-α、IL-6、MDA的表达,同时促进CAT、SOD和IL-10的表达。给予黄芪后,MAPK14、RB1、MAPK1、JUN和ATK1蛋白的表达水平显著降低,而IL2蛋白增加。

结论

黄芪可能通过其抗氧化作用作用于具有抗UC作用的靶点,并调节促炎和抗炎因子的平衡,从而成为治疗UC的有效药物。

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