Luteolin ameliorates ulcerative colitis in mice via reducing the depletion of NCR+ILC3 through Notch signaling pathway  

作　　者：XIE Xueqian LI Pengcheng ZHAO Meng XU Bo ZHANG Guixing WANG Qing NI Chen LUO Xia ZHOU Lian 

机构地区：[1]School of Pharmaceutical Sciences,Guangzhou University of Chinese Medicine,Guangzhou 510000,China [2]Shenzhen Bao'an Traditional Chinese Medicine Hospital,Guangzhou University of Chinese Medicine,Shenzhen 518000,China

出　　处：《Chinese Journal of Natural Medicines》2024年第11期991-1002,共12页中国天然药物（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.82074092);the Natural Science Foundation of Guangdong Province(No.2021A1515012219);Guangzhou University of Chinese Medicine“Double First-Class”and High-level University Discipline Collaborative Innovation Team Project(No.2021xk81).

摘　　要：The disorder of group 3 innate lymphoid cells(ILC3)subgroup,such as the predominance of NCR-ILC3 but the deple-tion of NCR+ILC3,is unfavorable to damaged intestinal barrier repair,which leads to the prolongations and obstinacy of ulcerative colitis(UC).Our previous studies had shown that luteolin promoted NCRILC3 differentitating into NCR+ILC3 to improving the de-pletion of NCR+ILC3 in UC mice,while the mechanism is unclear.This article aimed to explore the underlying mechanism of luteolin enhancing the proportion NCR+ILC3.UC mice model was established with 2%DSS and Notch signaling was blocked,then luteolin was used to intervene.The results showed that the effect of luteolin on ameliorating disease symptoms in UC mice,including inhibit-ing the weight loss,reducing the pathological damage of colon mucosa,etc.,was diminished with blocking Notch signaling pathway.In addition,luteolin increased the proportion of NCR+ILC3,NCR+MNK3 and IL-22+ILC3,decreased intestinal permeability,pro-moted mucin secretion,and promoted ZO-1 and Occludin expression,the above effect of luteolin was neutralized by Notch inhibitor LY-411575.Luteolin activated the abnormally blocked Notch signaling pathway in UC mice.And molecular docking predicted the af-finity of luteolin for RBPJ to be-7.5 kcal·mol^(-1 )in mouse,respectively;the affinity of luteolin for Notch1 and RBPJ was respectively scored to be-6.4 kcal·mol^(-1) and-7.7 kcal·mol^(-1) homo sapiens.These results proved that luteolin is positive for enhancing the propor-tion of NCR+ILC3 via Notch signaling,and it provides a basis for targeting NCR+ILC3 for restoring intestinal barrier function to alle-viating ulcerative colitis.

关 键 词：LUTEOLIN Ulcerative colitis Group 3 innate lymphoid cells NOTCH1 RBPJ 

分 类 号：R965[医药卫生—药理学]