Katsaros Ioannis, Sotiropoulou Maria, Vailas Michail, Papachristou Fotini, Papakyriakopoulou Paraskevi, Grigoriou Marirena, Kostomitsopoulos Nikolaos, Giatromanolaki Alexandra, Valsami Georgia, Tsaroucha Alexandra, Schizas Dimitrios
First Department of Surgery, National and Kapodistrian University of Athens, Laikon General Hospital, 11527 Athens, Greece.
Laboratory of Experimental Surgery, Faculty of Medicine, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
Nutrients. 2024 Dec 11;16(24):4282. doi: 10.3390/nu16244282.
Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder with no established pharmacotherapy. Quercetin, a polyphenolic flavonoid, demonstrates potential hepatoprotective effects but has limited bioavailability. This study evaluates the impact of quercetin on NAFLD and assesses the roles of autophagy-related proteins in disease progression. Forty-seven male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce NAFLD, followed by quercetin treatment for 4 weeks. Mice were divided into baseline, control, and two quercetin groups, receiving low (10 mg/kg) and high (50 mg/kg) doses. Liver histology was scored using the NAFLD Activity Score (NAS). Immunohistochemistry and immunoblotting were performed to analyze autophagy markers. Quercetin-treated groups showed significant reductions in NAS compared to controls ( = 0.011), mainly in steatosis and steatohepatitis. Immunohistochemistry indicated increased expression of autophagy markers LCA and p62 in quercetin groups. Western blot analysis revealed significant elevations in LC3A in the treated groups, suggesting improved autophagic activity and lipid degradation. Quercetin effectively reduces NAFLD severity and modulates autophagy-related proteins. These findings suggest that quercetin enhances autophagic flux, supporting its therapeutic potential for NAFLD. Additional research is needed to clarify the molecular mechanisms of quercetin and to determine the optimal dosing for clinical application.
非酒精性脂肪性肝病（NAFLD）是一种主要的代谢紊乱疾病，目前尚无成熟的药物治疗方法。槲皮素是一种多酚类黄酮，具有潜在的肝脏保护作用，但生物利用度有限。本研究评估了槲皮素对NAFLD的影响，并评估了自噬相关蛋白在疾病进展中的作用。47只雄性C57BL/6J小鼠被喂食高脂饮食（HFD）12周以诱导NAFLD，随后进行4周的槲皮素治疗。小鼠被分为基线组、对照组和两个槲皮素组，分别接受低剂量（10 mg/kg）和高剂量（50 mg/kg）的治疗。使用非酒精性脂肪性肝病活动评分（NAS）对肝脏组织学进行评分。进行免疫组织化学和免疫印迹分析以分析自噬标志物。与对照组相比，槲皮素治疗组的NAS显著降低（P = 0.011），主要体现在脂肪变性和脂肪性肝炎方面。免疫组织化学表明，槲皮素组自噬标志物LCA和p62的表达增加。蛋白质免疫印迹分析显示，治疗组中LC3A显著升高，表明自噬活性和脂质降解得到改善。槲皮素可有效降低NAFLD的严重程度并调节自噬相关蛋白。这些发现表明，槲皮素可增强自噬通量，支持其对NAFLD的治疗潜力。需要进一步的研究来阐明槲皮素的分子机制，并确定临床应用的最佳剂量。
