苦参碱：通过靶向HMGB1/NLRP3/半胱天冬酶-1通路治疗溃疡性结肠炎的一种有前景的疗法。
Matrine: A Promising Treatment for Ulcerative Colitis by Targeting the HMGB1/NLRP3/Caspase-1 Pathway.
作者信息
Sun Kexin, Lin Weiye, Hong Qianran, Chen Shuangyu, Li Jiayang, Qiu Shengliang
机构信息
The First School of Clinical Medicine, Zhejiang Chinese Medical University, 548 Binwen Rd, Hangzhou, 310053, P.R. China.
Zhejiang Provincial Hospital of Chinese Medicine, The First Affiliated Hospital of Zhejiang Chinese Medical University, 54 Youdian Rd, Hangzhou, 310006, P.R. China.
出版信息
Comb Chem High Throughput Screen. 2025;28(4):654-663. doi: 10.2174/0113862073292384240209095838.
BACKGROUND
Previous studies have found that matrine (MAT) effectively treated Ulcerative Colitis (UC). The purpose of this study is to explore its mechanism based on the HMGB1/NLRP3/Caspase-1 signaling pathway.
METHODS
MAT was administered intragastrically to DSS-induced UC mice for 14 days. The Disease Activity Index (DAI) and histological staining were measured to detect histopathological changes in colon. The levels of IL-1β, IL-6, and TNF-α in serum were measured by ELISA. The protein and mRNA expression of HMGB1/NLRP3/Caspase-1 in the colon were detected by immunohistochemistry, western Blotting or qRT-PCR.
RESULTS
MAT improved the histological pathological changes of UC mice, as assessed by DAI, colonic length, and colonic mucosal injury. MAT also reduced colonic inflammatory damage by reducing the serum IL-1β, IL-6, and TNF-α content and decreasing the expression of HMGB1, NLRP3, Caspase-1, and IL-1β and proteins and mRNA in the colon.
CONCLUSION
MAT could significantly alleviate DSS-induced UC symptoms by reducing the expressions of pro-inflammatory cytokines, such as IL-1β, TNF-α, and IL-6, the mechanism of which is related to the inhibition of HMGB1/NLRP3/Caspase-1 signaling pathway.
背景
先前的研究发现苦参碱（MAT）可有效治疗溃疡性结肠炎（UC）。本研究旨在基于HMGB1/NLRP3/半胱天冬酶-1信号通路探讨其作用机制。
方法
对用葡聚糖硫酸钠（DSS）诱导的UC小鼠进行为期14天的苦参碱灌胃给药。测量疾病活动指数（DAI）和组织学染色，以检测结肠的组织病理学变化。通过酶联免疫吸附测定（ELISA）测量血清中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的水平。通过免疫组织化学、蛋白质免疫印迹法（western Blotting）或实时定量聚合酶链反应（qRT-PCR）检测结肠中HMGB1/NLRP3/半胱天冬酶-1的蛋白质和信使核糖核酸（mRNA）表达。
结果
通过DAI、结肠长度和结肠黏膜损伤评估，苦参碱改善了UC小鼠的组织病理学变化。苦参碱还通过降低血清IL-1β、IL-6和TNF-α含量以及减少结肠中HMGB1、NLRP3、半胱天冬酶-1、IL-1β的蛋白质和mRNA表达，减轻了结肠炎症损伤。
结论
苦参碱可通过降低促炎细胞因子如IL-1β、TNF-α和IL-6的表达，显著减轻DSS诱导的UC症状，其机制与抑制HMGB1/NLRP3/半胱天冬酶-1信号通路有关。
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