Ma Miaomiao, Liang Leshi, Lin Meihong, Luo Canhua, Deng Xingfeng, Yu Changhui
Department of Gastroenterology, Zhujiang Hospital, the Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guandong 510282, China.
Department of Gastroenterology, the Second Provincial People's Hospital of Guangdong Province, Guangzhou, Guangdong 510317, China.
Biol Pharm Bull. 2025;48(3):246-261. doi: 10.1248/bpb.b24-00590.
Ulcerative colitis (UC) is a chronic inflammatory bowel disease without efficient treatment. Fuzi has anti-inflammatory and immunomodulatory properties. However, the bioactive compounds and mechanisms of fuzi in the treatment of UC are not completely understood. The active components of fuzi were retrieved from Traditional Chinese Medicine Database System Pharmacology and Analysis Platform; PharmMapper was used to predict the targets of the active components of fuzi; UC-related disease targets were obtained from Online Mendelian Inheritance in Man and Genecards databases, and Venny 2.1 was used to obtain common targets; Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed on the common targets using R 4.0.2. STRING and Cytoscape 3.9.0 was used to construct a protein-protein interaction (PPI) network for the intersection targets. We then determined the role of the candidate molecule from fuzi, Higenamine (Hig), in a mouse model of dextran sulfate sodium (DSS)-induced colitis. In total, 21 active components and 420 corresponding targets of fuzi were obtained, of which 224 common targets were identified by intersecting with UC-related targets. The GO, KEGG, and PPI results suggested that fuzi and Hig may target RAC-alpha serine/threonine-protein kinase (AKT) to regulate the phosphoinositide-3-kinase (PI3K)/AKT pathway in UC. Animal experiments have shown that Hig treatment greatly reduced DSS-induced colitis, as measured by the disease activity index score, colonic inflammation, and intestinal barrier integrity. Mechanistically, Hig downregulated the DSS-induced PI3K-AKT signaling pathway by inhibiting AKT phosphorylation. Altogether, Hig alleviated DSS-induced colitis in mice, possibly by inhibiting colon inflammation and improving the intestinal barrier by regulating the PI3K-AKT signaling pathway. The active component Hig from fuzi is likely to play a role in the treatment of UC.
溃疡性结肠炎（UC）是一种缺乏有效治疗方法的慢性炎症性肠病。附子具有抗炎和免疫调节特性。然而，附子治疗UC的生物活性成分和机制尚未完全明确。从中药数据库系统药理学与分析平台检索附子的活性成分；利用PharmMapper预测附子活性成分的靶点；从《人类孟德尔遗传在线》和Genecards数据库获取UC相关疾病靶点，并使用Venny 2.1获取共同靶点；使用R 4.0.2对共同靶点进行京都基因与基因组百科全书（KEGG）和基因本体论（GO）分析。使用STRING和Cytoscape 3.9.0构建交集靶点的蛋白质-蛋白质相互作用（PPI）网络。然后，我们在葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠模型中确定了附子中的候选分子去甲乌药碱（Hig）的作用。共获得21种附子活性成分及420个相应靶点，其中与UC相关靶点交叉鉴定出224个共同靶点。GO、KEGG和PPI结果表明，附子和Hig可能靶向RAC-α丝氨酸/苏氨酸蛋白激酶（AKT），以调节UC中的磷酸肌醇-3-激酶（PI3K）/AKT通路。动物实验表明，通过疾病活动指数评分、结肠炎症和肠屏障完整性测量，Hig治疗可大大减轻DSS诱导的结肠炎。从机制上讲，Hig通过抑制AKT磷酸化下调DSS诱导的PI3K-AKT信号通路。总之，Hig可能通过调节PI3K-AKT信号通路抑制结肠炎症并改善肠屏障，从而减轻小鼠DSS诱导的结肠炎。附子中的活性成分Hig可能在UC治疗中发挥作用。
