摘要
该研究拟通过“网络药理学预测-动物炎症改善分析-分子作用机制探索”等多个层面,研究大黄有效组分大黄酸与大黄素联合治疗溃疡性结肠炎(ulcerative colitis,UC)的药效及作用机制。采用网络药理学预测“大黄酸-大黄素”联合干预UC作用机制,筛选出52个潜在靶点,主要参与癌症通路、PI3K/AKT信号通路、癌症中microRNAs以及细胞凋亡通路,其中PI3K/AKT信号通路被报道与UC密切相关,为最佳的候选联合治疗通路;采用葡聚糖硫酸钠建立经典UC小鼠模型,记录空白组、模型组、大黄酸组、大黄素组、联合用药组、柳氮磺胺吡啶阳性药物给药后各治疗指标差异,结果显示,与模型组比较,大黄酸和大黄素联合用药组的小鼠体质量、疾病活动指数(DAI)、结肠长度、肿瘤坏死因子(TNF-α)、白细胞介素6(IL-6)、白细胞介素1β(IL-1β)和髓过氧化物酶(MPO)均有显著改善(P<0.01);结肠黏膜损伤显著降低;结肠组织p-PI3K/PI3K及p-AKT/AKT蛋白表达水平显著下调(P<0.01),且以上所有指标均较大黄酸/大黄素单独用药组效果更好;结合金氏Q值法评价其联合作用,其在结肠长度、TNF-α、IL-6、IL-1β、MPO、p-PI3K/PI3K及p-AKT/AKT的作用效果均大于1.15,说明大黄酸与大黄素具有协同作用。研究显示大黄酸与大黄素具有协同治疗UC作用,其作用机制可能与抑制PI3K/AKT通路及下调促炎因子有关,是值得关注的治疗UC新组分。
This study aimed to explore the efficacy and mechanism of combined rhein and emodin in the treatment of ulcerative colitis(UC)from the aspects of network pharmacology,animal inflammation improvement and molecular mechanism.Network pharmacology predicted that combined rhein and emodin acted on 52 potential targets,mainly participating in signaling pathways such as cancer,PI3 K/AKT,microRNAs in cancer and apoptosis.PI3 K/AKT signaling pathway has been reported to be closely related to UC,and the optimal candidate pathway for combined therapy.The UC mice model was established by dextran sodium sulfate,and then the modeled mice were randomly divided into control group,model group,rhein group,emodin group,rhein+emodin group and sulfasalazine group.After administration,compared with the conditions in model group,body weight,disease activity index(DAI)score,colon length,TNF-α,IL-6,IL-1βand myeloperoxidase(MPO)of mice in rhein+emodin group were improved(P<0.01);colonic mucosal injury was significantly reduced;the expression of p-PI3 K/PI3 K and p-AKT/AKT proteins were down-regulated(P<0.01).All the above indices were better than those in the rhein/emodin group alone.The Jin′s Q-values of the effect of combined rhein and emodin on colon length,TNF-α,IL-6,IL-1β,MPO,p-PI3 K/PI3 K and p-AKT/AKT were all greater than 1.15,which indicated that there was obvious synergistic effect between rhein and emodin.In all,rhein and emodin have synergistic effect in the treatment of UC,and the mechanism may be related to the inhibition of PI3 K/AKT signaling pathway and the down-regulation of proinflammatory factors.They are the new components in the treatment of UC,which is worthy of attention.
作者
高飞
钟辉云
陈可禧
董玲玲
林美斯
杜鸿灵
GAO Fei;ZHONG Hui-yun;CHEN Ke-xi;DONG Ling-ling;LIN Mei-si;DU Hong-ling(State Key Laboratory of Southesern Chinese Medicine Resources,School of Pharmacy,Chengdu Universiy of Traditional Chinese Medicine,Chengdu 61137,China;School of Medicine and Food,Sichuan Vocational College of Health and Rehabiliation,Zigong 643000,China;Department of Clinical Pharmacy,West China Hospital,Sichuan University,Chengdu 610041,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2022年第15期4148-4155,共8页
China Journal of Chinese Materia Medica
基金
国家自然科学基金青年基金项目(81903811)
四川省科技厅科技创新人才项目(2022JDRC0046)
中华中医药学会青年人才托举工程A类项目(2021-QNRC2-A09)。
