Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China.
School of Medicine, South China University of Technology, Guangzhou 510006, China.
Molecules. 2022 Dec 21;28(1):68. doi: 10.3390/molecules28010068.
Ulcerative colitis is a chronic inflammatory bowel disorder that is hard to cure once diagnosed. Bisdemethoxycurcumin has shown positive effects on inflammatory diseases. However, the underlying bioactive interaction between bisdemethoxycurcumin and ulcerative colitis is unclear. The objective of this study was to determine the core target and potential mechanism of action of bisdemethoxycurcumin as a therapy for ulcerative colitis. The public databases were used to identify potential targets for bisdemethoxycurcumin and ulcerative colitis. To investigate the potential mechanisms, the protein-protein interaction network, gene ontology analysis, and Kyoto encyclopedia of genes and genomes analysis have been carried out. Subsequently, experimental verification was conducted to confirm the findings. A total of 132 intersecting genes of bisdemethoxycurcumin, as well as ulcerative coli-tis-related targets, were obtained. SRC, EGFR, AKT1, and PIK3R1 were the targets of highest potential, and the PI3K/Akt and MAPK pathways may be essential for the treatment of ulcerative colitis by bisdemethoxycurcumin. Molecular docking demonstrated that bisdemethoxycurcumin combined well with SRC, EGFR, PIK3R1, and AKT1. Moreover, the in vitro experiments suggested that bisdemethoxycurcumin might reduce LPS-induced pro-inflammatory cytokines levels in RAW264.7 cells by suppressing PI3K/Akt and MAPK pathways. Our study provided a comprehensive overview of the potential targets and molecular mechanism of bisdemethoxycurcumin against ulcerative colitis. Furthermore, it also provided a theoretical basis for the clinical treatment of ulcerative colitis, as well as compelling evidence for further study on the mechanism of bisdemethoxycurcumin in the treatment of ulcerative colitis.
溃疡性结肠炎是一种难以治愈的慢性炎症性肠病。双去甲氧基姜黄素对炎症性疾病有积极作用。然而，双去甲氧基姜黄素与溃疡性结肠炎之间潜在的生物活性相互作用尚不清楚。本研究旨在确定双去甲氧基姜黄素作为溃疡性结肠炎治疗药物的核心靶点和潜在作用机制。利用公共数据库鉴定双去甲氧基姜黄素和溃疡性结肠炎的潜在靶点。为了探讨潜在机制，进行了蛋白质-蛋白质相互作用网络、基因本体分析和京都基因与基因组百科全书分析。随后进行了实验验证以确认研究结果。共获得 132 个双去甲氧基姜黄素的交集基因和溃疡性结肠炎相关靶点。SRC、EGFR、AKT1 和 PIK3R1 是最具潜力的靶点，PI3K/Akt 和 MAPK 通路可能是双去甲氧基姜黄素治疗溃疡性结肠炎的关键。分子对接表明双去甲氧基姜黄素与 SRC、EGFR、PIK3R1 和 AKT1 结合良好。此外，体外实验表明，双去甲氧基姜黄素可能通过抑制 PI3K/Akt 和 MAPK 通路降低 LPS 诱导的 RAW264.7 细胞中促炎细胞因子的水平。本研究全面概述了双去甲氧基姜黄素治疗溃疡性结肠炎的潜在靶点和分子机制。此外，还为溃疡性结肠炎的临床治疗提供了理论依据，并为进一步研究双去甲氧基姜黄素治疗溃疡性结肠炎的机制提供了有力证据。
