The Pharmacological Mechanism of Guchangzhixie Capsule Against Experimental Colitis.
The Pharmacological Mechanism of Guchangzhixie Capsule Against Experimental Colitis.
复制标题
古肠止泻胶囊抗实验性结肠炎的药理机制。
DOI：
10.3389/fphar.2021.762603
复制
发表时间：
2021
影响因子：
5.6
通讯作者：
Qin Z
中科院分区：
文献类型：
--
作者：
Yan J;Yu W;Lu C;Liu C;Wang G;Jiang L;Jiang Z;Qin Z
溃疡性结肠炎（UC）是炎症性肠病（IBD）的主要类型，其特征是免疫反应过度活跃和结直肠上皮破坏，伴有复杂的病理因素。固肠止泻胶囊（GCZX）已被纳入中国药典2020年版，已被广泛用于治疗UC。然而，潜在的分子机制尚未阐明。在本研究中，通过口服4%葡聚糖硫酸钠（DSS）5天，随后进行GCZX治疗另外15天，建立了实验性结肠炎小鼠模型。通过网络药理学分析，预测了固脉止痛胶囊的相关作用机制。进行细胞实验，检查GCZX治疗后肠类器官（IO）、巨噬细胞（Mφ）和人结肠上皮细胞（NCM 460细胞系）的功能变化。对来自小鼠模型的粪便进行16 S rRNA测序。采用液相色谱-质谱法（LC-MS）检测血清代谢物。结果，DSS诱导实验性结肠炎，并且这种诱导通过GCZX治疗减轻，如UC小鼠模型中挽救的病理症状所证明的，如直肠出血停止，白蛋白、白介素-17以及趋化因子（C-X-C基序）配体1（CXCL 1）水平降低，以及结肠长度缩短。网络药理学分析表明，GCZX靶基因在病原体诱导的感染、炎症途径以及肿瘤过程中富集。DSS处理降低了微生物多样性，导致病理细菌的积累，这是由GCZX胶囊逆转。基于微生物群组成的PICRUSt 2（通过重建未观察状态进行的社区系统发育调查）表明，GCZX治疗后传染病和癌症的发病率降低。与这些数据完全一致，GCZX给药抑制Mφ转化为促炎表型，减轻肿瘤坏死因子-α（TNFα）损害的IO功能，并减少上皮细胞对Mφ的募集。结论：GCZX胶囊是治疗UC的有效药物，其药理学机制涉及重建抗炎环境和促进粘膜愈合。
Ulcerative colitis (UC) is the major type of inflammatory bowel disease (IBD) characterized by an overactive immune response and destruction of colorectal epithelium with intricate pathological factors. Guchangzhixie (GCZX) capsule, included in the Chinese Pharmacopoeia 2020, has been widely utilized against UC. However, the underlying molecular mechanisms have not been elucidated. In the present study, a murine model of experimental colitis was established by orally feeding 4% dextran sodium sulfate (DSS) for 5 days and subsequently subjecting to GCZX treatment for another 15 days. Network pharmacology analysis was performed to predict the pertinent mechanisms of GCZX capsule. Cellular experiments examining the functional changes of intestinal organoids (IOs), macrophages (Mφs), and human colon epithelial cell cells (NCM460 cell line) after GCZX therapy were performed. Sequencing of 16S rRNA was conducted on the stools from the mouse model. Liquid chromatography-mass spectrometry (LC–MS) was utilized to detect serum metabolites. As a result, DSS induced experimental colitis, and this induction was alleviated by GCZX treatment, as evidenced by rescued pathological symptoms in UC mouse models, such as rectal bleeding stopping, decreased levels of albumin, interleukin-17, as well as chemokine (C-X-C motif) ligand 1 (CXCL1), and reduction in colon length. Network pharmacology analysis showed that GCZX-target genes were enriched in pathogen-induced infections, inflammatory pathways, as well as neoplastic processes. DSS treatment decreased microbial diversity and led to the accumulation of pathological bacterial, which was reversed by GCZX capsule. PICRUSt2 (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) based on profiles of microbiota composition demonstrated a decreased incidence of infectious disease and cancers after GCZX therapy. In full accordance with these data, GCZX administration suppressed Mφ transition to pro-inflammatory phenotype, alleviated tumor necrosis factor-α (TNFα)-compromised IOs functions, and decreased the recruitment of Mφs by epithelial cells. We conclude that GCZX capsule is an effective drug for UC and its pharmacological mechanisms involve re-establishing an anti-inflammatory milieu and favoring mucosal healing.
登录
查看更多内容
影响因子：
3
作者：
Chen, Yong;Wong, Ricky W. K.;Kao, Richard
通讯作者：
Kao, Richard
影响因子：
1.7
作者：
Kechin, Andrey;Boyarskikh, Uljana;Filipenko, Maxim
通讯作者：
Filipenko, Maxim
DOI：
10.1152/ajpregu.00442.2005
发表时间：
2006-01-01
影响因子：
2.8
作者：
Furlan, R;Ardizzone, S;Malliani, A
通讯作者：
Malliani, A
影响因子：
3.5
作者：
Endo, Mari;Hori, Masatoshi;Hanawa, Toshihiko
通讯作者：
Hanawa, Toshihiko
影响因子：
14.9
作者：
Hamosh, A;Scott, AF;McKusick, VA
通讯作者：
McKusick, VA