BACKGROUND 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 sedent...BACKGROUND 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.AIM 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.METHODS 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 highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,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.In vitro 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 pathwaymodulated 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.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.展开更多
目的观察盘龙七片对骨关节炎(osteoarthritis,OA)小鼠沉默信息转录调控因子(silent information regulator type 1,SIRT1)/核因子-κB(nuclear factor-kappa B,NF-κB)通路及软骨细胞凋亡的影响。方法手术切除右膝关节内侧半月板和前交...目的观察盘龙七片对骨关节炎(osteoarthritis,OA)小鼠沉默信息转录调控因子(silent information regulator type 1,SIRT1)/核因子-κB(nuclear factor-kappa B,NF-κB)通路及软骨细胞凋亡的影响。方法手术切除右膝关节内侧半月板和前交叉韧带复制小鼠OA模型。将小鼠分为正常对照组,模型组,阳性对照组,盘龙七片低、中、高剂量组。通过番红O-快速绿染色观察膝关节结构变化,进行Mankin评分评估关节炎严重程度,流式细胞术检测软骨细胞凋亡指数,qRT-PCR检测Bax、Bcl-2、Caspase-3 mRNA表达水平,Western blot法检测软骨细胞SIRT1、NF-κB蛋白表达水平。结果与正常对照组比较,模型组小鼠膝关节软骨细胞凋亡率增加,Bax、Caspase-3 mRNA和NF-κB蛋白表达水平显著增加,Bcl-2 mRNA和SIRT1蛋白表达水平显著降低,差异均有统计学意义(P<0.05);与模型组比较,阳性对照组与盘龙七片低、中、高剂量组小鼠膝关节软骨细胞凋亡率显著降低,Bax、Caspase-3 mRNA和NF-κB蛋白表达水平显著降低,Bcl-2 mRNA和SIRT1蛋白表达水平显著增加,差异均有统计学意义(P<0.05),盘龙七片的作用呈明显的剂量依赖性。结论盘龙七片可抑制OA小鼠膝关节软骨细胞凋亡,其作用机制可能与调节SIRT1/NF-κB信号通路相关。展开更多
基金the Scientific Research Project of Jiangsu Health Commission,No.Z2022078the Natural Science Foundation of Jiangsu Province,No.BK20220299.
文摘BACKGROUND 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.AIM 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.METHODS 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 highperformance liquid chromatography(HPLC)to identify the key components.RESULTS Ten primary chemical components of HQD were identified by HPLC analysis.In vivo,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.In vitro 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 pathwaymodulated 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.CONCLUSION In summary,our study confirmed that HQD mitigates lipid metabolism disorders and insulin resistance in NAFLD by triggering the Sirt1/NF-κB pathway.
