溃疡性结肠炎(ulcerative colitis,UC)是一种慢性非特异性炎症,中医药对UC的疗效确切.中药青黛发挥多靶点、复发率低、毒副作用较小的独特优势,对UC有较快缓解作用.青黛治疗UC微观分子机制可能涉及芳香烃受体/白介素-22(aryl hydrocarbon receptor/interleukin-22,AhR/IL-22)、核因子—红细胞2型相关因子/血红素氧合酶-1(nuclear factor erythroid 2-related factor 2/heme oxygenase-1,Nrf2/HO-1)、Janus 激酶/信号转导和转录激活因子 3(janus kinase/signal transducer and activator of transcription 3,JAK/STAT3)、转化生长因子 β/Smad(transforming growth factor β,TGF-β/Smad)、磷脂酰肌醇-3-激酶(phosphoinositide 3-kinase,PI3K)/蛋白激酶 B(protein kinase B,Akt)、有丝分裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、核因子-κB(nuclearfactor kappa-B,NF-κB)7条信号通路.大量动物实验、细胞实验证明,青黛及活性成分可通过直接作用于AhR然后激活AhR/IL-22信号通路,调节免疫反应,加强肠黏膜屏障功能;通过Nrf2/HO-1信号通路发挥抗氧化应激保护肠道屏障;通过JAK/STAT3信号通路调节辅助性T淋巴细胞17/调节性T淋巴细胞免疫平衡;通过NF-κB、MAPK信号通路发挥抗炎、抗细胞焦亡、保护紧密连接屏障作用;通过PI3K/Akt信号通路调节凋亡蛋白表达,预防UC相关癌症进展;通过TGF-β/Smad信号通路调节炎症因子,预防肠道纤维化等.现代分子生物学研究证实青黛及主要成分可通过调节相关信号通路相关分子的表达,降低肠道细胞的异常凋亡、分化及相关炎性因子的转录与释放,改善肠道稳态,加速溃疡愈合.本综述系统阐述青黛通过各信号通路调节机体免疫反应治疗UC,充分挖掘青黛活性成分及方剂的作用机制,为中医药发展提供理论基础.
Research progress of effect of Indigo naturalis in treatment of ulcerative colitis based on cell signaling pathway
Ulcerative colitis(UC)is a chronic non-specific inflammation,and traditional Chinese medicine(TCM)has a significant effect on UC.Indigo naturalis has the unique advantages of multiple targets,low recurrence rate and less toxic and side effects,and has a rapid remission effect on UC.The mechanism of UC may involve seven pathways including AHR/IL-22、Nrf2/HO-1、JAK/STAT3、TGF-β/Smad、MAPK、PI3K/Akt、NF-κB signaling pathway.A large number of animal experiments and cell experiments have proved that,Indigo naturalis and its active components can directly act on the AhR and then activate the AHR/IL-22 signaling pathway,to ate the immune response,to strengthen the intestinal mucosal barrier function;it protects the intestinal barrier against oxidative stress through the Nrf2/HO-1 signaling pathway;it regulates the immune balance of Th17/Treg through the JAK/STAT3 signaling pathway;it plays an anti-inflammatory,anti-pyroptosis and protective tight junction barrier role through NF-κB and MAPK signaling pathway;it regulates of apoptotic protein expression through the PI3K/Akt signaling pathway to prevent UC-related cancer progression;it regulates inflammatory factors through the TGF-β/Smad signaling pathway,to prevent intestinal fibrosis.Modern molecular biology studies have confirmed that Indigo naturalis and its main components can reduce the abnormal apoptosis,differentiation and transcription and release of intestinal cells and related inflammatory factors,improve intestinal homeostasis and accelerate ulcer healing.This review systematically expounds that Indigo naturalis regulates the immune response of the body to treat UC,fully excavates its active components and prescriptions,and provides a theoretical basis for the development of TCM.
万方数据
维普
