College of Pharmacy, Jiangsu Health Vocational College, Nanjing 211800, Jiangsu Province, China.
Department of Pathology, Affiliated Kunshan Hospital of Jiangsu University, Kunshan 215300, Jiangsu Province, China.
World J Gastroenterol. 2023 Aug 21;29(31):4744-4762. doi: 10.3748/wjg.v29.i31.4744.
Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological entity characterized by intrahepatic ectopic steatosis. As a consequence of increased consumption of high-calorie diet and adoption of a sedentary lifestyle, the incidence of NAFLD has surpassed that of viral hepatitis, making it the most common cause of chronic liver disease globally. Huangqin decoction (HQD), a Chinese medicinal formulation that has been used clinically for thousands of years, has beneficial outcomes in patients with liver diseases, including NAFLD. However, the role and mechanism of action of HQD in lipid metabolism disorders and insulin resistance in NAFLD remain poorly understood.
To evaluate the ameliorative effects of HQD in NAFLD, with a focus on lipid metabolism and insulin resistance, and to elucidate the underlying mechanism of action.
High-fat diet-induced NAFLD rats and palmitic acid (PA)-stimulated HepG2 cells were used to investigate the effects of HQD and identify its potential mechanism of action. Phytochemicals in HQD were analyzed by high-performance liquid chromatography (HPLC) to identify the key components.
Ten primary chemical components of HQD were identified by HPLC analysis. , HQD effectively prevented rats from gaining body and liver weight, improved the liver index, ameliorated hepatic histological aberrations, decreased transaminase and lipid profile disorders, and reduced the levels of pro-inflammatory factors and insulin resistance. studies revealed that HQD effectively alleviated PA-induced lipid accumulation, inflammation, and insulin resistance in HepG2 cells. In-depth investigation revealed that HQD triggers Sirt1/NF-κB pathway-modulated lipogenesis and inflammation, contributing to its beneficial actions, which was further corroborated by the addition of the Sirt1 antagonist EX-527 that compromised the favorable effects of HQD.
In summary, our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.
非酒精性脂肪性肝病（NAFLD）是一种以肝内异位脂肪沉积为特征的临床病理实体。随着高热量饮食的摄入增加和生活方式的久坐不动，NAFLD 的发病率已经超过了病毒性肝炎，成为全球最常见的慢性肝病病因。黄芩汤（HQD）是一种临床应用了数千年的中药方剂，对包括 NAFLD 在内的肝病患者具有有益的疗效。然而，HQD 在 NAFLD 脂质代谢紊乱和胰岛素抵抗中的作用和作用机制仍知之甚少。
评估 HQD 在 NAFLD 中的改善作用，重点关注脂质代谢和胰岛素抵抗，并阐明其作用机制。
使用高脂饮食诱导的 NAFLD 大鼠和棕榈酸（PA）刺激的 HepG2 细胞来研究 HQD 的作用，并确定其潜在的作用机制。通过高效液相色谱法（HPLC）分析 HQD 中的植物化学成分，以鉴定关键成分。
通过 HPLC 分析鉴定了 HQD 的十种主要化学成分。研究表明，HQD 能有效阻止大鼠体重和肝重增加，改善肝指数，改善肝组织学异常，降低转氨酶和脂质谱紊乱，并降低促炎因子和胰岛素抵抗水平。进一步的机制研究表明，HQD 能有效缓解 PA 诱导的 HepG2 细胞内脂质积累、炎症和胰岛素抵抗。深入研究表明，HQD 通过触发 Sirt1/NF-κB 通路调节的脂肪生成和炎症发挥其有益作用，这一作用进一步得到 Sirt1 拮抗剂 EX-527 的验证，该拮抗剂削弱了 HQD 的有利作用。
综上所述，我们的研究证实 HQD 通过触发 Sirt1/NF-κB 通路减轻 NAFLD 中的脂质代谢紊乱和胰岛素抵抗。
