Department of Gastroenterology, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, China.
Digestive Disease Center, The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, China.
Molecules. 2023 Jan 20;28(3):1060. doi: 10.3390/molecules28031060.
Cepharanthine (CEP), a bisbenzylisoquinoline alkaloid from tubers of Stephania, protects against some inflammatory diseases. Aconitate decarboxylase 1 (ACOD1) is also known as immune-responsive gene 1 (IRG1), which plays an important immunometabolism role in inflammatory diseases by mediating the production of itaconic acid. ACOD1 exhibits abnormal expression in ulcerative colitis (UC). However, whether CEP can combat UC by affecting ACOD1 expression remains unanswered. This study was designed to explore the protective effects and mechanisms of CEP in treating colitis through in vitro and in vivo experiments. In vitro assays indicated that CEP inhibited LPS-induced secretion of pro-inflammatory cytokines and ACOD1 expression in RAW264.7 macrophages. Additionally, in the mouse model of DSS-induced colitis, CEP decreased macrophage infiltration and ACOD1 expression in colon tissue. After treatment with antibiotics (Abx), the expression of ACOD1 changed with the composition of gut microbiota. Correlation analysis also revealed that Family-XIII-AD3011-group and Rumini-clostridium-6 were positively correlated with ACOD1 expression level. Additionally, data of the integrative Human Microbiome Project (iHMP) showed that ACOD1 was highly expressed in the colon tissue of UC patients and this expression was positively correlated with the severity of intestinal inflammation. Collectively, CEP can counter UC by modulating gut microbiota and inhibiting the expression of ACOD1. CEP may serve as a potential pharmaceutical candidate in the treatment of UC.
石蒜裂碱（CEP）是从石蒜属植物块茎中提取的一种双苄基异喹啉生物碱，具有抗炎作用。异柠檬酸裂解酶 1（ACOD1）也称为免疫反应基因 1（IRG1），通过介导异柠檬酸的产生，在炎症性疾病中发挥重要的免疫代谢作用。ACOD1 在溃疡性结肠炎（UC）中表达异常。然而，CEP 是否可以通过影响 ACOD1 的表达来治疗 UC 尚不清楚。本研究通过体外和体内实验设计旨在探讨 CEP 治疗结肠炎的保护作用及其机制。体外实验表明，CEP 抑制 LPS 诱导的 RAW264.7 巨噬细胞中促炎细胞因子的分泌和 ACOD1 的表达。此外，在 DSS 诱导的结肠炎小鼠模型中，CEP 减少了结肠组织中的巨噬细胞浸润和 ACOD1 的表达。用抗生素（Abx）处理后，ACOD1 的表达随肠道微生物群的组成而变化。相关性分析还表明，Family-XIII-AD3011 组和 Rumini-clostridium-6 与 ACOD1 的表达水平呈正相关。此外，整合人类微生物组计划（iHMP）的数据显示，ACOD1 在 UC 患者的结肠组织中高表达，并且这种表达与肠道炎症的严重程度呈正相关。综上所述，CEP 通过调节肠道微生物群和抑制 ACOD1 的表达来对抗 UC。CEP 可能成为治疗 UC 的潜在药物候选物。
