Furan based synthetic chalcone derivative functions against gut inflammation and oxidative stress demonstrated in in-vivo zebrafish model

• Published in: European journal of pharmacology 2023-10, Vol.957, p.175994-175994, Article 175994
• Main Authors: Nayak, S.P. Ramya Ranjan, Dhivya, L.S., R, Reshma, Almutairi, Bader O., Arokiyaraj, Selvaraj, Kathiravan, M.K., Arockiaraj, Jesu
• Format: Article
• Language: English
• Subjects: Antioxidant; Chalcone; Gut inflammation; Inflammatory bowel disease; Oxidative stress
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2023.175994

Inflammatory Bowel Disease (IBD) is a group of persistent intestinal illnesses resulting from bowel inflammation unrelated to infection. The prevalence of IBD is rising in industrialized countries, increasing healthcare costs. Whether naturally occurring or synthetic, chalcones possess a broad range of biological properties, including anti-inflammatory, anti-microbial, and antioxidant effects. This investigation focuses on DKO7 (E)-3-(4-(dimethylamino)phenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one, a synthesized chalcone with potential anti-inflammatory effects in a zebrafish model of intestinal inflammation induced by Dextran sodium sulfate (DSS). The in vitro study displayed dose-dependent anti-inflammatory as well as antioxidant properties of DKO7. Additionally, DKO7 protected zebrafish larvae against lipid peroxidation, reactive oxygen stress (ROS), and DSS-induced inflammation. Moreover, DKO7 reduced the expression of pro-inflammatory genes, including TNF-α, IL-1β, IL-6, and iNOS. Further, it reduced the levels of nitric oxide (NO) and lactate dehydrogenase (LDH) in the intestinal tissues of adult zebrafish and increased the levels of antioxidant enzymes such as Catalase (CAT) and superoxide dismutase (SOD). The protective effect of DKO7 against chemically (or DSS) induced intestinal inflammation was further verified using histopathological techniques in intestinal tissues. The furan-based chalcone derivative, DKO7, displayed antioxidant and anti-inflammatory properties. Also, DKO7 successfully reverses the DSS-induced intestinal damage in zebrafish. Overall, this study indicates the ability of DKO7 to alleviate DSS-induced gut inflammation in an in-vivo zebrafish. [Display omitted] •(E)-3-(4-(dimethylamino)phenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (named DKO7) displayed anti-inflammaion in in-vitro.•DKO7 protected in-vivo zebrafish larvae model from dextran sulfate sodium (DSS) induced ROS, lipid peroxidation and cellular apoptosis.•DKO7 increased production of antioxidant enzymes and decreased the production of LDH and NO in the intestinal tissues.•DKO7 reduced the expression of proinflammatory biomarkers in vivo intestinal tissue.•DKO7 restored the histoarchitecture of the intestine in the 9nflammatory bowel disease (IBD) in vivo model.