摘要Coptis chinensis Franch.and Panax ginseng C.A.Mey.are traditional herbal medicines with millennia of documented use and broad therapeutic applications,including anti-diabetic properties.However,the synergistic effect of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng on type 2 diabetes mellitus(T2DM)and its underlying mechanism remain unclear.The research demonstrated that the optimal ratio of total alkal-oids from Coptis chinensis and total ginsenosides from Panax ginseng was 4∶1,exhibiting max-imal efficacy in improving insulin resistance and gluconeogenesis in primary mouse hepato-cytes.This combination demonstrated significant synergistic effects in improving glucose tol-erance,reducing fasting blood glucose(FBG),the weight ratio of epididymal white adipose tissue(eWAT),and the homeostasis model assessment of insulin resistance(HOMA-IR)in leptin receptor-deficient(db/db)mice.Subsequently,a T2DM liver-specific network was con-structed based on RNA sequencing(RNA-seq)experiments and public databases by integrat-ing transcriptional properties of disease-associated proteins and protein-protein interactions(PPIs).The network recovery index(NRI)score of the combined treatment group with a 4∶1 ratio exceeded that of groups treated with individual components.The research identified that activated adenosine 5'-monophosphate-activated protein kinase(AMPK)/acetyl-CoA carboxylase(ACC)signaling in the liver played a crucial role in the synergistic treatment of T2DM,as verified by western blot experiment in db/db mice.These findings demonstrate that the 4∶1 combination of total alkaloids from Coptis chinensis and total ginsenosides from Panax ginseng significantly improves insulin resistance and glucose and lipid metabolism disorders in db/db mice,surpassing the efficacy of individual treatments.The synergistic mechanism correlates with enhanced AMPK/ACC signaling pathway activity.