Diabetes, Metabolic Syndrome and Obesity (Mar 2023)
Ginsenoside Rg1 Ameliorates Pancreatic Injuries via the AMPK/mTOR Pathway in vivo and in vitro
Abstract
Jin Chen,1,* Guoping Zhu,2,* Wenbo Xiao,3 Xiaosong Huang,4 Kewu Wang,2 Yi Zong2 1Department of Hematology, Yiwu Central Hospital, Yiwu, People’s Republic of China; 2Department of Radiology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Department of Pharmacy, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kewu Wang; Yi Zong, Department of Radiology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, No. N1, Shangcheng Avenue, Yiwu, Zhejiang, People’s Republic of China, Email [email protected]; [email protected]: The main propanaxatriol-type saponin found in ginseng (Panax ginseng C. A. Mey), ginsenoside Rg1 (G-Rg1), has bioactivities that include anti-inflammatory, antioxidant, and anti-diabetic properties. This study aimed to investigate the effects of G-Rg1 on streptozotocin (STZ)-induced Type 1 Diabetes mellitus (T1DM) mice and the insulin-secreting cell line in RIN-m5F cells with high-glucose (HG) treatment.Methods: The STZ-induced DM mice model was treated with G-Rg1 alone or combined with 3-Methyladenine (3-MA, an autophagy inhibitor)/rapamycin (RAPA, an autophagy activator) for 8 weeks, and levels of glucose and lipid metabolism, histopathological changes, as well as autophagy and apoptosis of relevant markers were estimated. In vitro, the HG-induced RIN-m5F cells were treated with G-Rg1, 3-MA, and Compound C (CC), an AMPK inhibitor, or their combinations to estimate the influences on cell apoptosis, autophagy, and AMPK/mTOR pathway-associated target gene levels.Results: G-Rg1 treatment attenuated glucose and lipid metabolism disorder and pancreatic fibrosis in diabetic mice. In addition, subdued autophagy and p-AMPK protein expression, and enhanced p-mTOR protein expression and apoptosis levels in TIDM mice and HG-induced RIN-m5F cells were ameliorated by G-Rg1 treatment. Furthermore, these anti-apoptosis effects of G-Rg1 were partially abolished by 3-MA and CC.Conclusion: Our findings revealed that G-Rg1 exhibits strong anti-apoptosis ability in pancreatic tissues of type 1 diabetic mice and HG-induced RIN-m5F cells, and the mechanisms involved in activating AMPK and inhibiting mTOR-mediated autophagy, indicating that G-Rg1 may have the therapeutic and preventive potential for treating pancreatic injury in diabetic patients.Keywords: diabetes mellitus, ginsenoside Rg1, autophagy, apoptosis, AMPK
