Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China.
Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, Anhui Institute of Innovative Drugs, School of Pharmacy, Anhui Medical University, Hefei 230032, China; School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Hefei 230032, China.
Int Immunopharmacol. 2021 Jun;95:107471. doi: 10.1016/j.intimp.2021.107471. Epub 2021 Mar 20.
Alcoholic liver disease (ALD) is the most common chronic liver disease worldwide. Currently, there is no definitive treatment for alcohol-induced liver injury (ALI). Inflammatory response and oxidative stress play a crucial role in ALI. Cyclooxygenase 2 (COX-2) can be induced by inflammation and it has been reported that the enhanced expression of COX-2 in alcoholic liver injury. Rutaecarpine (RUT) was extracted from evodia rutaecarpa. RUT has a wide range of pharmacological activities. In order to increase its anti-inflammatory activity, our group introduced sulfonyl group to synthesized the 3-[2-(trifluoromethoxy)benzenesulfonamide]-rutaecarpine (3-B-RUT). In this study, we explored the protective effect of 3-B-RUT on alcoholic liver injury in vivo and in vitro and preliminarily explore its mechanism. Mice ALI model was established according to the chronic-plus-binge ethanol model. Results showed that 3-B-RUT (20 μg/kg) attenuated alcohol-induced liver injury and suppressed liver inflammation and oxidative stress, and the effect was comparable to RUT (20 mg/kg). In vitro results are consistent with in vivo results. Mechanistically, the 3-B-RUT might suppress inflammatory response and oxidative stress by regulating activation of NF-κB/COX-2 pathway. In summary, 3-B-RUT, a derivative of RUT, may be a promising clinical candidate for ALI treatment.
酒精性肝病（ALD）是全球最常见的慢性肝病。目前，对于酒精性肝损伤（ALI）尚无明确的治疗方法。炎症反应和氧化应激在 ALI 中起着关键作用。环氧化酶 2（COX-2）可被炎症诱导，有报道称 COX-2 在酒精性肝损伤中的表达增强。吴茱萸碱（RUT）从吴茱萸中提取。RUT 具有广泛的药理活性。为了提高其抗炎活性，我们小组在合成时引入了磺酰基，得到了 3-[2-（三氟甲氧基）苯磺酰胺]-吴茱萸碱（3-B-RUT）。本研究旨在探讨 3-B-RUT 对体内和体外酒精性肝损伤的保护作用，并初步探讨其机制。根据慢性加 binge 乙醇模型建立了小鼠 ALI 模型。结果表明，3-B-RUT（20μg/kg）可减轻酒精诱导的肝损伤，抑制肝炎症和氧化应激，作用与 RUT（20mg/kg）相当。体内结果与体外结果一致。在机制上，3-B-RUT 可能通过调节 NF-κB/COX-2 通路的激活来抑制炎症反应和氧化应激。综上所述，RUT 的衍生物 3-B-RUT 可能是治疗 ALI 的有前途的临床候选药物。
