Área de Farmacologia, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, MT, Brazil; Key Laboratory of Economic Plants and Biotechnology and the Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, PR China.
Área de Histologia e Biologia Celular, Departamento de Ciências Básicas em Saúde, Faculdade de Medicina, Universidade Federal de Mato Grosso (UFMT), Cuiabá, MT, Brazil.
Biochem Pharmacol. 2021 Apr;186:114490. doi: 10.1016/j.bcp.2021.114490. Epub 2021 Feb 27.
Canthin-6-one (Cant) is an indole alkaloid found in several botanical drugs used as medicines, reported to be gastroprotective, anti-inflammatory, anti-microbial, anti-diarrheal and anti-proliferative. We aimed to explore Cant in the management of colitis using a trinitrobenzenesulfonic acid (TNBS)-induced rat model. Cant (1, 5 and 25 mg/kg) was administered by oral gavage to Wistar rats followed by induction of colitis with TNBS. Macroscopic and histopathological scores, myeloperoxidase (MPO), malondialdehyde (MDA) and reduced glutathione (GSH) were assessed in colon tissues. Pro- (TNF-α, IL-1β and IL-12p70) and anti-inflammatory (IL-10) cytokines, and vascular endothelial growth factor (VEGF) were also quantified. Mitogen-activated protein kinase 14 (MAPK14) and Toll-like receptor-8 (TLR8), as putative targets, were considered through in silico analysis. Cant (5 and 25 mg/kg) reduced macroscopic and histological colon damage scores in TNBS-treated rats. MPO and MDA were reduced by up to 61.69% and 92.45%, respectively, compared to TNBS-treated rats alone. Glutathione concentration was reduced in rats administered with TNBS alone (50.00% of sham group) but restored to 72.73% (of sham group) with Cant treatment. TNF-α, IL-1β, IL-12p70 and VEGF were reduced, and anti-inflammatory IL-10 was increased following Cant administration compared to rats administered TNBS alone. Docking ligation results for MAPK14 (p38α) and TLR8 with Cant, confirmed that these proteins are feasible putative targets. Cant has an anti-inflammatory effect in the intestine by down-regulating molecular immune mediators and decreasing oxidative stress. Therefore, Cant could have therapeutic potential for the treatment of inflammatory bowel disease and related syndromes.
卡亭碱（Cant）是几种用作药物的植物药中发现的吲哚生物碱，据报道具有胃保护、抗炎、抗微生物、抗腹泻和抗增殖作用。我们旨在使用三硝基苯磺酸（TNBS）诱导的大鼠模型探索 Cant 在结肠炎管理中的作用。Cant（1、5 和 25mg/kg）通过口服灌胃给予 Wistar 大鼠，然后用 TNBS 诱导结肠炎。评估结肠组织中的髓过氧化物酶（MPO）、丙二醛（MDA）和还原型谷胱甘肽（GSH）、促炎（TNF-α、IL-1β 和 IL-12p70）和抗炎（IL-10）细胞因子以及血管内皮生长因子（VEGF）。通过计算机分析考虑了有丝分裂原激活蛋白激酶 14（MAPK14）和 Toll 样受体-8（TLR8）这两个潜在靶点。Cant（5 和 25mg/kg）降低了 TNBS 处理大鼠的宏观和组织学结肠损伤评分。与单独用 TNBS 处理的大鼠相比，MPO 和 MDA 分别降低了 61.69%和 92.45%。用 TNBS 单独处理的大鼠的谷胱甘肽浓度降低（仅为假手术组的 50.00%），但用 Cant 处理后恢复到 72.73%（假手术组）。与单独用 TNBS 处理的大鼠相比，TNF-α、IL-1β、IL-12p70 和 VEGF 减少，抗炎性 IL-10 增加。Cant 对 MAPK14（p38α）和 TLR8 与 Cant 的对接配体结果证实，这些蛋白是可行的潜在靶点。Cant 通过下调分子免疫介质和减少氧化应激对肠道具有抗炎作用。因此，Cant 可能具有治疗炎症性肠病和相关综合征的潜力。
