地榆乙醇提取物抑制JAK2/STAT3信号通路改善溃疡性结肠炎  

Ethanolic extract of Sanguisorba officinalis improves ulcerative colitis via inhibition of JAK2/STAT3 pathway

作　　者：龚雷强 李聪聪 雷浩然 王栋 邓赟[1] 郭大乐 GONG Leiqiang;LI Congcong;LEI Haoran;WANG Dong;DENG Yun;GUO Dale(State Key Laboratory of Southwestern Chinese Medicine Resource,School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,Sichuan;School of Basic Medical Sciences,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,Sichuan)

机构地区：[1]成都中医药大学药学院西南特色中药资源国家重点实验室,成都611137 [2]成都中医药大学基础医学院,成都611137

出　　处：《中药与临床》2024年第5期28-36,共9页Pharmacy and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金青年项目(82204603);成都中医药大学“杏林学者”学科人才科研提升计划项目(ZDZX2022002)。

摘　　要：目的:本研究旨在探究地榆乙醇提取物的主要化学成分及其治疗溃疡性结肠炎的活性评价及作用机制。方法:通过高分辨液相质谱联用技术鉴别地榆乙醇提取物中主要化学成分;ICR小鼠随机分为空白对照组、DSS模型组、地榆乙醇提取物高、中、低剂量组和美沙拉嗪阳性药组,3%DSS水溶液诱导溃疡性结肠炎小鼠模型,每天观察和记录小鼠的体重、粪便状态和便血情况。组织切片H&E、PAS染色观察各组小鼠结肠组织病理学变化。RT-qPCR和Western blot探究地榆乙醇提取物治疗溃疡性结肠炎的作用机制。结果:高分辨液相质谱联用鉴别出地榆乙醇提取物中鞣质、酚酸、黄酮、黄酮苷、萜类及其皂苷衍生物等共49种化合物成分。地榆乙醇提取物有效改善结肠萎缩和临床症状;H&E和PAS染色表明其能减轻结肠组织炎症细胞的浸润,黏膜上皮细胞的坏死脱落,肠腺隐窝结构及肠黏液层屏障的破坏;显著降低M1巨噬细胞相关的促炎细胞因子mRNA转录水平(IL-1β、IL-6、iNOS和TNF-α),并促进M2巨噬细胞相关的抗炎细胞因子mRNA转录(IL-10、TGF-β和ARG-1);地榆乙醇提取物有效下调JAK2/STAT3信号通路上IL-1β、iNOS、JAK2和P-STAT3关键蛋白的表达水平。结论:本研究基于高分辨液相质谱联用技术,鉴定出地榆乙醇提取物中49种主要化学成分。地榆提取物可通过调节结肠组织M1/M2型巨噬细胞相关细胞因子的平衡和抑制JAK2/STAT3信号通路,发挥保护作用。地榆乙醇提取物未来有望成为治疗UC的有效药物。Objective:The purpose of this study is to investigate the primary chemical composition of the ethanolic extract of Sanguisorba officinalis(SOE)and its activity assessment and mechanism of action in the treatment of ulcerative colitis.Methods:The primary chemical constituents in the SOE were identified using high-resolution liquid chromatography-mass spectrometry(UPLC-Q-Orbitrap-HRMS).ICR mice were randomly grouped into the control group,the DSS model group,the SOE at high,medium and low doses and the positive drug group of Mesalazine.3%DSS solution induced ulcerative colitis’s model in mice and the body weight,faecal characteristics and hemafecal condition were recorded daily.H&E and PAS staining of tissue sections were performed to observe the histopathological lesions in the colon.RT-qPCR and Western blot were conducted to investigate the mechanism of action of SOE in the treatment of ulcerative colitis.Results:A total of 49 compounds,including tannins,phenolic acids,flavonoids,flavonoid glycosides,terpenoids and their saponin derivatives,were identified in the SOE by UPLC-Q-Orbitrap-HRMS.SOE effectively improved colonic atrophy and clinical symptoms.H&E and PAS staining showed that it reduced the infiltration of inflammatory cells in the colonic tissue,the necrotic shedding of mucosal epithelial cells and the disruption of the crypt structure and intestinal mucus layer barrier.SOE significantly reduced mRNA transcript levels of pro-inflammatory cytokines associated with the M1 macrophage(IL-1β,IL-6,iNOS and TNF-α)and promoted mRNA transcripts of anti-inflammatory cytokines associated with the M2 macrophage(IL-10,TGF-βand ARG-1).Finally,SOE markedly down-regulated the expression levels of key proteins of IL-1β,iNOS,JAK2 and P-STAT3 in the JAK2/STAT3 pathway.Conclusion:Based on UPLC-Q-Orbitrap-HRMS,49 primary chemical components are identified in SOE.SOE exhibit protective effects by regulating the balance of M1/M2 associated macrophage cytokines and inhibiting JAK2/STAT3 pathway in colonic tissue.SOE is a

关 键 词：地榆乙醇提取物 高分辨液相质谱联用 溃疡性结肠炎 JAK2/STAT3信号通路 

分 类 号：R285[医药卫生—中药学] R282[医药卫生—中医学]