改良版葛根芩連湯（MGQD）最早在《傷寒論》中被記錄下來，被認為是治療潰瘍性結腸炎（UC）的經典處方。然而，它對UC的保護機制仍需完全阐明。本研究旨在探讨MGQD对戊糖钠硫酸盐（DSS）诱导的UC小鼠和肿瘤坏死因子α（TNF-α）诱导的Caco-2细胞单层肠道屏障模型的影响和潜在分子机制。使用LC-MS/MS技术鉴定了MGQD和MGQD药物含量血清（葛根芩連湯药物血清）的化学成分。基于体重、疾病活动指数（DAI）、结肠长度、结肠组织病理损伤、炎症因子、氧化应激反应和肠道屏障功能评价了MGQD对DSS诱导的UC的治疗作用。使用细胞计数试剂盒（CCK-8）检测MGQD-DS对Caco-2细胞存活率的影响。此外，在体外建立了TNF-α诱导的Caco-2细胞单层肠道屏障模型。将空白血清或MGQD-DS施加于Caco-2细胞单层，以观察MGQD-DS对TEER、FITC-二硫苯氨酸渗透性、炎症因子、氧化应激指标和肠上皮屏障（IEB）的影响。结果表明，MGQD通过下调白细胞介素（IL）-1β和丙二醛（MDA）的表达，减轻杯状细胞的丢失、肠道上皮超微结构的破坏，并上调超氧化物歧化酶（SOD）、过氧化物酶（CAT）、谷胱甘肽（GSH）、紧密连接蛋白-1（ZO-1）、闭隙蛋白、克拉汀-1和Ep-差素的表达，显著改善了UC小鼠的症状和病理损伤。在体外实验中，MGQD-DS显著降低了TNF-α诱导的Caco-2细胞单层FITC-二硫苯氨酸的通透性，增加了TEER，抑制了IL-21、IL-17A和MDA的表达，促进了IL-4、IL-10、转化生长因子-β（TGF-β）、SOD、CAT、GSH、闭隙蛋白和Ep-差素的表达。因此，MGQD可以改善DSS诱导的UC小鼠和TNF-α诱导的Caco-2细胞单层肠道屏障模型，其保护作用与其抑制炎症、减轻氧化应激和修复肠道屏障损伤有关。版权所有 © 2023 Elsevier B.V. 发布。

Modified Gegen Qinlian decoction (MGQD), which was first documented in Treatise on Febrile Disease, is recognized as a classic prescription to treat ulcerative colitis (UC). However, its protective mechanism against UC remains to be fully elucidated.To explore the impact and the potential molecular mechanism of MGQD on dextran sodium sulfate (DSS)-induced UC mice and tumor necrosis factor alpha (TNF-α)-induced Caco-2 cell monolayer model of intestinal barrier.The chemical components of MGQD and MGQD drug containing serum (MGQD-DS) were characterized by LC-MS/MS. The therapeutic effect of MGQD on DSS-induced UC was evaluated based on body weight, disease activity index (DAI), colon length, colonic histopathological injury, inflammatory cytokines, oxidative stress response and intestinal barrier function. Cell Counting Kit (CCK)-8 assay was applied to detect the effect of MGQD-DS on the viability of Caco-2 cells. Additionally, TNF-α-induced Caco-2 cell monolayer model of intestinal barrier was established in vitro. The Caco-2 cell monolayers were administered blank serum or MGQD-DS to observe the effects of MGQD-DS on transepithelial electrical resistance (TEER), permeability of fluorescein isothiocyanate (FITC)-dextran, inflammatory cytokines, oxidative stress indicators and intestinal epithelial barrier (IEB).MGQD significantly improved symptoms and pathological damage in UC mice by downregulating the expression of interleukin (IL)-1β and malondialdehyde (MDA), attenuating the loss of goblet cells and the destruction of intestinal epithelial ultrastructure, and upregulating the expression of superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), zonula occludens-1 (ZO-1), Occludin, Claudin-1 and E-cadherin. In vitro, MGQD-DS significantly reduced the flux of FITC-dextran, increased the TEER, inhibited the expression of IL-21, IL-17A and MDA, and promoted the expression of IL-4, IL-10, transforming growth factor-β (TGF-β), SOD, CAT, GSH, Occludin and E-cadherin in TNF-α-induced Caco-2 cell monolayer model of intestinal barrier.MGQD can ameliorate DSS-induced UC mice and TNF-α-induced Caco-2 cell monolayer model of intestinal barrier, and the protective effect is related to its inhibition of inflammation, alleviation of oxidative stress, and repair of intestinal barrier damage.Copyright © 2023. Published by Elsevier B.V.