The present study aimed to increase the content of minor ginsenosides and enhance the anti-colorectal cancer activity of ginsenosides via biotransformation by Lactiplantibacillus plantarum MB11 screened from fermented foods. A subcutaneous transplantation tumor model of murine colorectal cancer CT26 cells was established in mice to study the anticarcinogenic activities and mechanism of fermented total ginsenosides (FTGs). The results showed that L. plantarum MB11 fermentation increased the content of minor ginsenosides and decreased that of major ginsenosides. FTGs reduced the tumor weight and size compared with the model group. Immunofluorescence and TdT-mediated dUTP nick end labeling (TUNEL) analysis showed that FTGs significantly increase the number of caspase-3 cells in tumor tissue and induce cell apoptosis. Mechanically, FTGs activate AMPK/mTOR autophagy pathway and regulate JAK2/STAT3 and Bax/Bcl-2/caspase-3 apoptosis pathway. Overall, fermentation with L. plantarum MB11 enhanced minor ginsenosides in total ginsenosides, and FTGs induced subcutaneous transplantation tumor autophagy and apoptosis in mice.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by glycolipid dysregulation and hepatic steatosis. Centella asiatica (CA) and its triterpenoid constituents exert metabolic benefits. In addition, previous metabolomics study found that asiatic acid regulated pyrimidine metabolism in obese mice, while the key target and pathway were undefined. This study investigated the regulatory effects of CA and its active constituents on T2DM-related glycolipid disorders, focusing on the pyrimidine metabolism pathway. T2DM mice were established using a high-fat diet combined with streptozotocin (STZ) and treated with Centella asiatica ethanolic extract or asiatic acid (AA), with glibenclamide as a positive control. Then, glycolipid metabolism, hepatic function, pyrimidine metabolites, and related mechanisms were assessed using biochemical assays, LC–MS/MS, cellular experiments, molecular analyses, and molecular docking. CAE and AA significantly reduced FBG (decreased by 51.01% and 53.01%), improved glucose intolerance, corrected dyslipidemia, alleviated hepatic steatosis, and attenuated insulin resistance in T2DM mice. They elevated hepatic uridine, cytidine, and UDP-glucose (UDPG) levels, promoted glycogen synthesis, inhibited uridine phosphorylase 1 (UPP1) activity, upregulated UDPG synthesis genes (PGM1, UGP2), and downregulated lipogenic genes (ACACA, Fasn, SREBP1/2). Molecular docking indicated specific binding of AA and asiaticoside to UPP1. This work distinguishes from our prior research by identifying UPP1 as a functional target and elucidating the detailed molecular mechanism. CA improves T2DM-associated glycolipid disorders and hepatic injury by modulating the pyrimidine metabolism-UDPG-glycogen synthesis pathway and targeting UPP1, highlighting its therapeutic potential for metabolic diseases.