溃疡性结肠炎（UC）是一种累及肠管的疾病，其特征是慢性炎症反应。黄连碱（COP）是黄连的独特成分，具有抗炎、抗氧化、抗菌、抗癌等功效。早期研究证实COP是治疗结肠炎的一种有前景的药物，但结肠炎的发病机制和COP的治疗靶点还不够阐明。在本次后续研究中，我们采用右旋糖酐硫酸钠（DSS）诱导的UC模型来进一步阐明COP对小鼠UC的可能机制。采用COP和阳性药物柳氮磺胺吡啶(SASP)口服灌胃建立DSS诱导的结肠炎小鼠模型。评估了氧化应激、炎症细胞因子、肠道屏障通透性、TXNIP/NLRP3炎症小体途径的蛋白表达和肠道微生物组结构。在这项研究中，我们的团队发现COP可以减轻DSS引起的小鼠UC，并显着改善体重减轻、疾病活动指数、肠道通透性（血清二胺氧化酶和 D-乳酸）、收缩结肠长度和组织学改变。此外，COP大大降低了结肠组织中促炎因子、丙二醛（MDA）活性和活性氧（ROS）水平的产生，同时增加了超氧化物歧化酶（SOD）活性。此外，COP 下调了硫氧还蛋白相互作用蛋白 (TXNIP)、NOD 样受体蛋白 3 (NLRP3)、凋亡相关斑点样蛋白 (ASC)、caspase-1、IL-1β 和 IL-18 的蛋白质表达。肠道微生物组测序表明，DSS 和 COP 对 DSS 诱发的 UC 小鼠肠道微生物的组成和多样性产生巨大影响。此外，COP还提高了益生菌Bacteroidota、Akkermansia_muciniphila和Bacteroides_acidifaciens的丰度，降低了潜在致病菌的比例，如Lachnospiraceae、Acetatifactor_muris、Clostridium_XlVa、Alistipes和Oscillibacter，并降低了Bacillota/Bacteroidota的比例，这极大地帮助逆转了肠道微生物群达到平衡状态。这些细菌的变化与结肠炎相对指数密切相关。COP抗UC的机制与抑制TXNIP/NLRP3炎症小体信号通路和调整肠道微生物组有关。这些证明为 COP 的反 UC 功能提供了新的理解，COP 可能是对抗 UC 的潜在候选者。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Ulcerative colitis (UC) is a disease involving the enteric canal which is characterised by chronisch inflammatory reaction. Coptisine (COP), the distinctive component of Coptis chinensis Franch., is famous for its anti-inflammation, antioxidation, anti-bacteria, and anti-cancer. Earlier researches certified that COP is a prospective remedy for colitis, but the mechanism of colitis and the therapeutical target of COP are deficiently elucidated.In this follow-up study, we adopted dextran sulfate sodium (DSS)-elicited UC model to further elucidate the possible mechanism of COP on UC in mice.COP and the positive drug sulfasalazine (SASP) were administered by oral gavage in DSS-induced colitis mouse model. Oxidative stress, inflammatory cytokines, intestinal barrier permeability, protein expression of the TXNIP/NLRP3 inflammasome pathway and intestinal microbiome structure were assessed.Among this investigation, our team discovered that COP could mitigate DSS-elicited UC in murines, with prominent amelioration in weight loss, disease activity index, intestinal permeability (serum diamine oxidase and D-lactate), contracted colonal length and histologic alterations. Furthermore, COP greatly lowered the generation of pro-inflammatory factors, malondialdehyde (MDA) activity and reactive oxygen species (ROS) level, while increased superoxide dismutase (SOD) activity in colonal tissues. Additionally, COP downmodulated the proteic expressions of thioredoxin-interacting protein (TXNIP), NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, IL-1β and IL-18. Enteric microbiome sequencing displayed that DSS and COP tremendously influenced the constitution and diversity of enteric microbes in DSS-elicited UC murines. Besides, COP elevated the abundance of probiotic bacteria Bacteroidota, Akkermansia_muciniphila and Bacteroides_acidifaciens, lowered the proportions of potential pathogenic bacteria, such as Lachnospiraceae, Acetatifactor_muris, Clostridium_XlVa, Alistipes and Oscillibacter, and reduced the ratio of Bacillota/Bacteroidota, which vastly helped to reverse the enteric microbiome to a balanceable condition. Alterations in these bacteria were strongly correlated with the colitis relative index.The mechanism of COP against UC is connected with the suppression of TXNIP/NLRP3 inflammasome signalling pathway and the adjustment of the enteric microbiome profiles. The proofs offer new understandings upon the anti-UC function of COP, which might be a prospective candidate against UC.Copyright © 2024 Elsevier B.V. All rights reserved.