Objective:Metabolic syndrome is a complex medical condition that has become an alarming epidemic,but an effective therapy for this disease is still lacking.The use of the herbal formula Huangqisan(HQS)to treat diabetes is documented in the Chinese medical literature as early as 1117 A.D.;however,its therapeutic effects and underlying mechanisms remain elusive.Methods:To investigate the beneficial effects of HQS on metabolic disorders,high-fat diet-induced obe-sity(DIO),leptin receptor dysfunction(db/db)and low-density lipoprotein receptor-knockout(LDLR-/)mice were used.Obese mice were treated with either HQS or vehicle.Blood,liver tissue,white fat tissue and brown adipose tissue were harvested at the end of the treatment.Metabolic disease-related param-eters were evaluated to test effects of HQS against diabetes,obesity and hyperlipidemia.Aortic arches from LDLR-/-mice were analyzed to investigate the effects of HQS on atherosclerosis.RNA-sequence,quantitative real-time polymerase chain reaction and Western blot were performed to investigate the mechanisms of HQS against metabolic disorder.Results:HQS lowered body weight,fasting blood glucose and serum lipid levels and improved glucose tolerance and insulin sensitivity in DIO mice and db/db mice(P＜0.05).HQS also blocked atherosclerotic plaque formation in LDLR-/-mice.HQS suppressed de novo lipid synthesis by reducing the expression of messenger RNA for sterol regulatory element-binding factor 1,stearyl coenzyme A desaturase 1 and fatty acid synthase,and enhancing adenosine 5'-monophosphate-activated protein kinase signaling in both in vivo and in vitro experiments,indicating potential mechanisms for HQS's activity against diabetes.Conclusion:HQS is effective for reversing metabolic disorder and has the potential to be used as therapy for metabolic syndrome.