Lee Yongjun, Kwon Dong-Joo, Kim Young Han, Ra Moonjin, Heo Seong Il, Ahn Won Gyeong, Park Jeong-Ran, Lee Seoung Rak, Kim Ki Hyun, Kim Sun Young
Hongcheon Institute of Medicinal Herb, 101 Yeonbongri, Hongcheon, Republic of Korea.
School of Pharmacy, Sungkyunkwan University, Suwon, Korea.
PLoS One. 2017 Nov 1;12(11):e0185134. doi: 10.1371/journal.pone.0185134. eCollection 2017.
Chronic alcohol consumption causes alcohol-induced lipogenesis and promotes hepatic injury by preventing the oxidation of hepatocellular fatty acids through the suppression of the activation of AMP-activated protein kinase (AMPK). HIMH0021, an active flavonoid compound, which is a component of the Acer tegmentosum extract, has been shown to protect against liver damage caused by alcohol consumption. Therefore, in this study, we aimed to determine whether HIMH0021 could regulate alcoholic fatty liver and liver injury in mice. Oral administration of 10 days of Lieber-DeCarli ethanol plus a single binge of 30% ethanol (chronic-plus-binge model) induced steatosis and liver injury and inflammation in mice, which appears similar to the condition observed in human patients with alcohol-related diseases. HIMH0021, which was isolated from the active methanol extract of A. tegmentosum, inhibited alcohol-induced steatosis and attenuated the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during hepatocellular alcohol metabolism, both of which promote lipogenesis as well as liver inflammation. Treatment with HIMH0021 conferred protection against lipogenesis and liver injury, inhibited the expression of cytochrome P4502E1, and increased serum adiponectin levels in the mice subjected to chronic-plus-binge feeding. Furthermore, in hepatocytes, HIMH0021 activated fatty acid oxidation by activating pAMPK, which comprises pACC and CPT1a. These findings suggested that HIMH0021 could be used to target a TNFα-related pathway for treating patients with alcoholic hepatitis.
长期饮酒会导致酒精性脂肪生成，并通过抑制腺苷酸活化蛋白激酶（AMPK）的激活来阻止肝细胞脂肪酸的氧化，从而促进肝损伤。HIMH0021是一种活性黄酮类化合物，是青皮槭提取物的一种成分，已被证明可预防饮酒引起的肝损伤。因此，在本研究中，我们旨在确定HIMH0021是否能调节小鼠的酒精性脂肪肝和肝损伤。口服10天的Lieber-DeCarli乙醇加一次30%乙醇的暴饮（慢性加暴饮模型）可诱导小鼠脂肪变性、肝损伤和炎症，这与酒精相关疾病患者的情况相似。从青皮槭的活性甲醇提取物中分离出的HIMH0021，在肝细胞酒精代谢过程中抑制了酒精诱导的脂肪变性，并降低了丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）的血清水平，这两种酶都促进脂肪生成和肝脏炎症。用HIMH0021治疗可保护小鼠免受脂肪生成和肝损伤，抑制细胞色素P4502E1的表达，并提高慢性加暴饮喂养小鼠的血清脂联素水平。此外，在肝细胞中，HIMH0021通过激活包括pACC和CPT1a的pAMPK来激活脂肪酸氧化。这些发现表明，HIMH0021可用于靶向肿瘤坏死因子α相关途径来治疗酒精性肝炎患者。
