Radosavljevic Tatjana, Brankovic Milica, Djuretić Jasmina, Grujic-Milanovic Jelica, Kovacic Marijana, Jevtic Jovan, Stankovic Sanja, Samardzic Janko, Vucevic Danijela, Jakovljevic Vladimir
Institute of Pathophysiology "Ljubodrag Buba Mihailović", Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Int J Mol Sci. 2024 Dec 26;26(1):86. doi: 10.3390/ijms26010086.
Alcohol-associated liver disease (ALD) is a common non-communicable chronic liver disease characterized by a spectrum of conditions ranging from steatosis and alcohol-associated steatohepatitis (AH) to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The pathogenesis of ALD involves a complex interplay of various molecular, biochemical, genetic, epigenetic, and environmental factors. While the mechanisms are well studied, therapeutic options remain limited. Alpinetin, a natural flavonoid with antioxidant and anti-inflammatory properties, has shown potential hepatoprotective effects, though its efficacy in ALD remains unexplored. This study investigated the hepatoprotective effects of alpinetin using a Lieber-DeCarli ethanol liquid diet model of ALD in C57BL/6 mice. Mice were divided into three groups: the control group, the ethanol group, and the ethanol group treated with alpinetin. Serum activity of ALT, AST, γ-GT, and ALP was measured to assess liver function, along with antioxidative and oxidative/nitrosative stress markers in liver tissue. Pro-inflammatory cytokines and endoplasmic reticulum (ER) stress parameters in liver tissue were also evaluated. Histological assessment of disease activity was performed using the SALVE grading and staging system. Treatment with alpinetin significantly reduced serum levels of ALT, AST, γ-GT, and oxidative/nitrosative stress markers while increasing antioxidative markers. The levels of pro-inflammatory cytokines and ER stress parameters were significantly decreased. Histological analysis demonstrated reduced steatosis, hepatocyte ballooning, and inflammation. These findings suggest that alpinetin holds promise as a potential therapeutic agent for managing ALD.
酒精性肝病（ALD）是一种常见的非传染性慢性肝病，其特征是一系列病症，从脂肪变性和酒精性脂肪性肝炎（AH）到纤维化、肝硬化和肝细胞癌（HCC）。ALD的发病机制涉及多种分子、生化、遗传、表观遗传和环境因素的复杂相互作用。虽然其机制已得到充分研究，但治疗选择仍然有限。高山黄芩素是一种具有抗氧化和抗炎特性的天然黄酮类化合物，已显示出潜在的肝脏保护作用，不过其在ALD中的疗效仍未得到探索。本研究使用C57BL/6小鼠的ALD Lieber-DeCarli乙醇液体饮食模型研究了高山黄芩素的肝脏保护作用。将小鼠分为三组：对照组、乙醇组和用高山黄芩素治疗的乙醇组。测量血清谷丙转氨酶（ALT）、谷草转氨酶（AST）、γ-谷氨酰转肽酶（γ-GT）和碱性磷酸酶（ALP）活性以评估肝功能，同时检测肝组织中的抗氧化和氧化/亚硝化应激标志物。还评估了肝组织中的促炎细胞因子和内质网（ER）应激参数。使用SALVE分级和分期系统对疾病活动进行组织学评估。用高山黄芩素治疗可显著降低血清ALT、AST、γ-GT水平和氧化/亚硝化应激标志物，同时增加抗氧化标志物。促炎细胞因子水平和ER应激参数显著降低。组织学分析显示脂肪变性、肝细胞气球样变和炎症减轻。这些发现表明，高山黄芩素有望成为治疗ALD的潜在治疗药物。
