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基于呋喃的合成查尔酮衍生物在体内斑马鱼模型中对抗肠道炎症和氧化应激的作用。

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

机构信息

Toxicology and Pharmacology Laboratory, Department of Biotechnology, Faculty of Science and Humanities, SRM Institute of Science and Technology, Kattankulathur, 603203, Chengalpattu District, Tamil Nadu, India.

Department of Pharmaceutical Chemistry, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, 603203, Chengalpattu District, Tamil Nadu, India.

出版信息

Eur J Pharmacol. 2023 Oct 15;957:175994. doi: 10.1016/j.ejphar.2023.175994. Epub 2023 Aug 23.

Abstract

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.

摘要

炎症性肠病(IBD)是一组由与感染无关的肠道炎症引起的慢性肠道疾病。在工业化国家,IBD 的患病率正在上升,导致医疗保健成本增加。查耳酮无论是天然存在的还是合成的,都具有广泛的生物学特性,包括抗炎、抗菌和抗氧化作用。本研究关注 DKO7(E)-3-(4-(二甲氨基)苯基)-1-(5-甲基呋喃-2-基)-2-丙烯-1-酮,一种合成查尔酮,在葡聚糖硫酸钠(DSS)诱导的斑马鱼肠道炎症模型中具有潜在的抗炎作用。体外研究显示 DKO7 具有剂量依赖性的抗炎和抗氧化特性。此外,DKO7 可保护斑马鱼幼虫免受脂质过氧化、活性氧应激(ROS)和 DSS 诱导的炎症。此外,DKO7 降低了促炎基因 TNF-α、IL-1β、IL-6 和 iNOS 的表达。此外,它降低了成年斑马鱼肠道组织中一氧化氮(NO)和乳酸脱氢酶(LDH)的水平,并增加了抗氧化酶如 Catalase(CAT)和超氧化物歧化酶(SOD)的水平。DKO7 对化学物质(或 DSS)诱导的肠道炎症的保护作用也通过肠道组织的组织病理学技术得到了进一步验证。呋喃基查尔酮衍生物 DKO7 具有抗氧化和抗炎作用。此外,DKO7 成功地逆转了 DSS 诱导的斑马鱼肠道损伤。总的来说,这项研究表明 DKO7 能够减轻体内斑马鱼 DSS 诱导的肠道炎症。

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