Zhang Pengcheng, Ma Dongshen, Wang Yongchen, Zhang Miao, Qiang Xiaoyan, Liao Min, Liu Xie, Wu Hui, Zhang Yubin
State Key Laboratory of Natural Medicines, Department of Biochemistry, China Pharmaceutical University, Nanjing 210009, China.
Food Chem Toxicol. 2014 Dec;74:225-32. doi: 10.1016/j.fct.2014.10.005.
Alcohol consumption is customary in many cultures and it is a common human behavior worldwide. Binge ethanol and chronic alcohol consumption, two usual drinking patterns of human beings, produce a state of oxidative stress in liver and disturb the liver function. However, a safe and effective therapy for alcoholic liver disease in humans is still elusive. This study identified the natural product berberine as a potential agent for treating or preventing ethanol-induced liver injury. We demonstrated that berberine attenuated oxidative stress resulted from binge drinking in liver by reducing hepatic lipid peroxidation, glutathione exhaust and mitochondrial oxidative damage. Furthermore, berberine also prevented the oxidative stress and macrosteatosis in response to chronic ethanol exposure in mice. Either the total cytochrome P450 2E1 or the mitochondria-located cytochrome P450 2E1, which is implicated in ethanol-mediated oxidative stress, was suppressed by berberine. On the other hand, berberine significantly blunted the lipid accumulation in liver due to chronic alcohol consumption, at least partially, through restoring peroxisome proliferator-activated receptor α/peroxisome proliferator-activated receptor-gamma Co-activator-1α and hepatocyte nuclear factor 4α/microsomal triglyceride transfer protein pathways. These findings suggested that berberine could serve as a potential agent for preventing or treating human alcoholic liver disease.
饮酒在许多文化中都很常见，是一种全球普遍的人类行为。暴饮乙醇和长期饮酒是人类常见的两种饮酒模式，会在肝脏中产生氧化应激状态并扰乱肝功能。然而，一种安全有效的人类酒精性肝病治疗方法仍然难以找到。本研究确定天然产物黄连素是一种治疗或预防乙醇诱导的肝损伤的潜在药物。我们证明，黄连素通过减少肝脏脂质过氧化、谷胱甘肽耗竭和线粒体氧化损伤，减轻了暴饮在肝脏中引起的氧化应激。此外，黄连素还能预防小鼠长期乙醇暴露后的氧化应激和大脂肪变性。黄连素抑制了与乙醇介导的氧化应激有关的总细胞色素P450 2E1或位于线粒体的细胞色素P450 2E1。另一方面，黄连素至少部分地通过恢复过氧化物酶体增殖物激活受体α/过氧化物酶体增殖物激活受体γ共激活因子-1α和肝细胞核因子4α/微粒体甘油三酯转移蛋白途径，显著减轻了长期饮酒导致的肝脏脂质积累。这些发现表明，黄连素可作为预防或治疗人类酒精性肝病的潜在药物。
