Zanthoxylum alkylamides improves hepatic glucose metabolism by regulating gut microbiota in STZ-induced T2DM rats

The observed beneficial impact of Zanthoxylum alkylamides (ZA) in addressing Type 2 diabetes mellitus (T2DM) suggests a potential association with short-chain fatty acids (SCFAs) and gut microbial composition. This study systematically investigated the influence of ZA on the organ index, c-peptide and lipid levels, gut microbiota composition, SCFAs production, and hepatic glucose metabolism in T2DM rats. The results indicate the success of ZA in treating T2DM rats characterized by hepatomegaly, nephromegaly, elevated blood lipids, and suppressed c-peptide levels. Following ZA intervention, the capacity of T2DM rats to produce SCFAs was not only restored but exceeded normal levels. Additionally, there was an augmentation in gut bacteria diversity, with a heightened abundance of Proteobacteria and an elevated Firmicutes/Bacteroidetes ratio. Conversely, a reduction in Actinobacteria abundance was noted. Importantly, ZA demonstrated the ability to regulate insulin activity and alleviate T2DM by activating the PI3K/Akt/mTOR signaling pathway in the liver of rats. In summary, our research reveals promising avenues for managing T2DM, encompassing diagnostic, therapeutic, monitoring, and drug discovery methodologies.