Notoginsenoside R1 promotes Lgr5^(+) stem cell and epithelium renovation in colitis mice via activating Wnt/β-Catenin signaling  

作　　者：Zhi-lun Yu Rui-yang Gao Cheng Lv Xiao-long Geng Yi-jing Ren Jing Zhang Jun-yu Ren Hao Wang Fang-bin Ai Zi-yi Wang Bei-bei Zhang Dong-hui Liu Bei Yue Zheng-tao Wang Wei Dou 

机构地区：[1]The MOE Key Laboratory of Standardization of Chinese Medicines,Shanghai Key Laboratory of Compound Chinese Medicines,and the SATCM Key Laboratory of New Resources and Quality Evaluation of Chinese Medicines,Institute of Chinese Materia Medica,Shanghai University of Traditional Chinese Medicine(SHUTCM),Shanghai,201203,China [2]Centre for Chinese Herbal Medicine Drug Development Limited,Hong Kong Baptist University,Hong Kong SAR,China

出　　处：《Acta Pharmacologica Sinica》2024年第7期1451-1465,共15页中国药理学报（英文版）

基　　金：supported by the National Natural Science Foundation of China (82274329 to WD;81920108033 to ZTW);the China Postdoctoral Science Foundation (2023M732336 to BY);the Shanghai Science and Technology Committee Sailing Program Foundation (23YF1442500 to BY).

摘　　要：Inflammatory bowel disease(IBD)is characterized by persistent damage to the intestinal barrier and excessive inflammation,leading to increased intestinal permeability.Current treatments of IBD primarily address inflammation,neglecting epithelial repair.Our previous study has reported the therapeutic potential of notoginsenoside R1(NGR1),a characteristic saponin from the root of Panax notoginseng,in alleviating acute colitis by reducing mucosal inflammation.In this study we investigated the reparative effects of NGR1 on mucosal barrier damage after the acute injury stage of DSS exposure.DSS-induced colitis mice were orally treated with NGR1(25,50,125 mg·kg^(-1)·d^(-1))for 10 days.Body weight and rectal bleeding were daily monitored throughout the experiment,then mice were euthanized,and the colon was collected for analysis.We showed that NGR1 administration dose-dependently ameliorated mucosal inflammation and enhanced epithelial repair evidenced by increased tight junction proteins,mucus production and reduced permeability in colitis mice.We then performed transcriptomic analysis on rectal tissue using RNA-sequencing,and found NGR1 administration stimulated the proliferation of intestinal crypt cells and facilitated the repair of epithelial injury;NGR1 upregulated ISC marker Lgr5,the genes for differentiation of intestinal stem cells(ISCs),as well as BrdU incorporation in crypts of colitis mice.In NCM460 human intestinal epithelial cells in vitro,treatment with NGR1(100μM)promoted wound healing and reduced cell apoptosis.NGR1(100μM)also increased Lgr5+cells and budding rates in a 3D intestinal organoid model.We demonstrated that NGR1 promoted ISC proliferation and differentiation through activation of the Wnt signaling pathway.Co-treatment with Wnt inhibitor ICG-001 partially counteracted the effects of NGR1 on crypt Lgr5^(+) ISCs,organoid budding rates,and overall mice colitis improvement.These results suggest that NGR1 alleviates DSS-induced colitis in mice by promoting the regeneration of Lgr5^(+) stem cel

关 键 词：inflammatory bowel disease notoginsenoside R1 intestinal stem cells Wnt/β-Catenin pathway ICG-001 

分 类 号：R96[医药卫生—药理学]