二氢杨梅素通过改变脂质代谢和增强乙醇代谢来保护肝脏。,Alcoholism: Clinical & Experimental Research

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二氢杨梅素通过改变脂质代谢和增强乙醇代谢来保护肝脏。
Alcoholism: Clinical & Experimental Research Pub Date : 2020-04-08 , DOI: 10.1111/acer.14326
Joshua Silva ₁ , Xin Yu ₁ , Renita Moradian ₁ , Carson Folk ₁ , Maximilian H Spatz ₁ , Phoebe Kim ₁ , Adil A Bhatti ₁ , Daryl L Davies ₁ , Jing Liang ₁

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背景过量饮酒（乙醇，EtOH）是慢性肝病的一个重要原因，占美国肝硬化相关死亡人数的近一半。EtOH 诱导的肝毒性与 EtOH 代谢及其相关的促炎细胞因子增加、氧化应激以及随后的枯否细胞活化有关。二氢杨梅素 (DHM) 是一种从枳椇中分离的生物类黄酮，可以减少乙醇中毒并可能防止化学性肝损伤。但是，关于 DHM 对乙醇代谢和肝脏保护的影响的信息仍然很少。因此，目前的研究检验了以下假设：补充 DHM 可增强 EtOH 代谢并减少 EtOH 介导的脂质失调，从而促进肝细胞健康。方法使用雄性 C57BL/6J 小鼠和强制饮酒随意 EtOH 喂养模型和 HepG2/VL-17A 肝母细胞瘤细胞模型评估 DHM（5 和 10 mg/kg；腹腔注射）的保肝作用。EtOH 介导的脂质积累和 DHM 对脂质沉积的影响是通过 H&E 染色、甘油三酯测量和细胞内脂质染料确定的。通过蛋白质印迹和蛋白质阵列确定磷酸化/总蛋白质以及血清和肝细胞因子的蛋白质表达。使用肝脏匀浆的总 NAD+ /NADH 测定来检测 NAD + 水平。结果 DHM 减少了长期喂食乙醇的小鼠的肝脂肪变性、肝甘油三酯和肝损伤标志物。DHM 处理导致 AMPK 和下游靶标、肉碱棕榈酰转移酶 (CPT)-1a、和乙酰辅酶A羧化酶（ACC）-1。DHM 诱导 EtOH 代谢酶的表达并降低 EtOH 和乙醛浓度，部分原因可能是 NAD+ 的变化。此外，DHM 降低了血清和细胞模型中促炎细胞因子和趋化因子的表达。结论总之，这些发现支持将 DHM 作为膳食补充剂，通过改变脂质代谢、增强 EtOH 代谢和抑制炎症反应来减少 EtOH 诱导的肝损伤，从而促进肝脏健康。

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Dihydromyricetin Protects the Liver via Changes in Lipid Metabolism and Enhanced Ethanol Metabolism.

BACKGROUND Excess alcohol (ethanol, EtOH) consumption is a significant cause of chronic liver disease, accounting for nearly half of the cirrhosis-associated deaths in the United States. EtOH-induced liver toxicity is linked to EtOH metabolism and its associated increase in proinflammatory cytokines, oxidative stress, and the subsequent activation of Kupffer cells. Dihydromyricetin (DHM), a bioflavonoid isolated from Hovenia dulcis, can reduce EtOH intoxication and potentially protect against chemical-induced liver injuries. But there remains a paucity of information regarding the effects of DHM on EtOH metabolism and liver protection. As such, the current study tests the hypothesis that DHM supplementation enhances EtOH metabolism and reduces EtOH-mediated lipid dysregulation, thus promoting hepatocellular health. METHODS The hepatoprotective effect of DHM (5 and 10 mg/kg; intraperitoneal injection) was evaluated using male C57BL/6J mice and a forced drinking ad libitum EtOH feeding model and HepG2/VL-17A hepatoblastoma cell models. EtOH-mediated lipid accumulation and DHM effects against lipid deposits were determined via H&E stains, triglyceride measurements, and intracellular lipid dyes. Protein expression of phosphorylated/total proteins and serum and hepatic cytokines was determined via Western blot and protein array. Total NAD+ /NADH Assay of liver homogenates was used to detect NAD + levels. RESULTS DHM reduced liver steatosis, liver triglycerides, and liver injury markers in mice chronically fed EtOH. DHM treatment resulted in increased activation of AMPK and downstream targets, carnitine palmitoyltransferase (CPT)-1a, and acetyl CoA carboxylase (ACC)-1. DHM induced expression of EtOH-metabolizing enzymes and reduced EtOH and acetaldehyde concentrations, effects that may be partly explained by changes in NAD+ . Furthermore, DHM reduced the expression of proinflammatory cytokines and chemokines in sera and cell models. CONCLUSION In total, these findings support the utility of DHM as a dietary supplement to reduce EtOH-induced liver injury via changes in lipid metabolism, enhancement of EtOH metabolism, and suppressing inflammation responses to promote liver health.

更新日期：2020-04-08

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