Arginyl-fructosyl-glucose (AFG), a major Maillard reaction product of red ginseng, improved kidney and pancreatic injury in vitro and in vivo in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) has been associated with kidney fibrosis becoming the major cause of diabetic nephropathy, leading to end-stage kidney diseases (ESKD) worldwide. To date, although the roots of ginseng (Panax ginseng C.A. Meyer) have revealed nephroprotective and antidiabetic activities, including Arginyl-Fructosyl Glucose (AFG), a non-saponin compound of red ginseng, the mechanism of action involved in diabetic nephropathy specifically remains unclear. This study was designed to assess the ameliorative effects of AFG In vitro and In vivo on kidney injury in T2DM mice induced by high-fat diet (HFD) + sucrose/Streptozotocin (STZ). The results showed that AFG significantly attenuated fasting blood glucose (FBG), body weight variation, and food and water consumption. Furthermore, the histopathological and immunofluorescence analyses combined with mRNA and protein expressions in HEK293 cells and T2DM mice revealed the ability of AFG to improve glucose and lipid metabolism, and inflammation. AFG also alleviated apoptosis, oxidative stress, and insulin resistance by upregulating PI3K/AKT, p38 MAPK/ERK and insulin-like signaling pathways in cross-talk with the TGF-β/Smad signaling pathway. Overall, AFG could improve kidney and pancreatic injury on HFD + sucrose/STZ-induced T2DM through the downregulation of TGF-β, involved in kidney fibrosis, and Smads, act as his downstream mediator. It is thus suggesting that AFG could become a novel therapeutic drug for T2DM and its complications.