Berberine(BBR)is a natural compound isolated from Coptis chinensis and for decades an over-the-count medicine in China for bacterial-caused diarrhea.We have identified BBR to be an effective drug in treating hyperlipidemia as well as hyperglycemia.Clinical studies showed that oral administration of BBR caused significant reduction of blood cholesterol,LDL-c,triglyceride,as well as glucose and HbA1c in patients with hyperlipidemia or T2D.A small%of patients have minor and transient side-effect in the GI system.The cholesterol-lowering effect was associated with the ERK mediated LDLR m RNA up-regulation;the glucose-lowering effect mainly resulted from PKD-mediated insulin receptor expression as well as activation of AMPK.The clinical efficacy of BBR were verified by a large number of independent clinical groups in and outside China.For BBR absorption mechanism,we showed that BBR was first converted into dh BBR by nitroreductase in the gut microbiota,promoting BBR enter into intestinal well,where it was oxidized back to BBR,and then got into blood.Our recent study showed that BBR could also promote gut microbiota pathways to make SCFAs(such as butyrate),which entered blood and reduced blood lipids and glucose,suggesting a newly identified MOA of BBR.BBR is now in clinical trial in China.We consider it a multiple-target drug for metabolic disorders in clinic. Berberine (BBR) is a natural compound isolated from Coptis chinensis and for decades an over-the-count medicine in China for bacterial-caused diarrhea. We have identified BBR to be effective drug in treating hyperlipidemia as well as hyperglycemia. Clinical findings showed that oral administration of BBR caused significant reduction of blood cholesterol, LDL-c, triglyceride, as well as glucose and HbA1c in patients with hyperlipidemia or T2D. A small% of patients have minor and transient side-effect in the GI system.The cholesterol -lowering effect was associated with the ERK mediated LDLR m RNA up-regulation; the glucose-lowering effect primarily due from PKD-mediated insulin receptor expression as well as activation of AMPK. The clinical efficacy of BBR were verified by a large number of independent clinical groups in and outside China. For BBR absorption mechanism, we showed that BBR was first converted into dh BBR by nitroreductase in the gut microbiota, promoting BBR enter into intestinal we ll, where it was oxidized back to BBR, and then got into blood. Our recent study showed that BBR could also promote gut microbiota pathways to make SCFAs (such as butyrate), which entered blood and reduced blood lipids and glucose, suggesting newly identified MOA of BBR.BBR is now in clinical trial in China. We consider it a multiple-target drug for metabolic disorders in clinic.