Ginsenoside R3 alleviates non-alcoholic fatty liver disease by regulating the PPARγ/miR-103-3p pathway

Purpose: To determine the effect of ginsenoside R3 (Rg3) on non-alcoholic fatty liver disease (NAFLD), and the mechanism involved. Methods: High-fat diet (HFD) was used to establish an NAFLD mouse model. The mice were daily and intraperitoneally injected with Rg3 at a dose of 1 mg/kg. Blood lipid levels and levels of liver inflammatory markers were measured by enzyme-linked immunosorbent assay (ELISA) while liver pathological changes and lipid accumulation were assessed with hematoxylin-eosin (H&E) staining and oil red O staining, respectively. The mRNA and protein expressions of miR-103-3p and PPARγ were determined with quantitative real-time polymerase chain reaction (qPCR) and western blot assay, respectively. Furthermore, an in vitro hepatocyte NAFLD model was established, and Rg3 was used to treat the cells; PPARγ was overexpressed in the cells. Lipid accumulation, inflammatory factors, as well as PPARγ and miR-103-3p expressions were assessed as indicated for the in vivo studies above. Apoptosis was determined by flow cytometry. Results: Rg3 alleviated the NAFLD-induced decreases in liver function, reversed NAFLD-mediated pathological injury in liver tissue injury, and decreased hepatic lipid build-up and inflammatory lesions (p < 0.05). It also significantly reversed the upregulation of PPARγ and miR-103-3p in the liver tissue of NAFLD mice. At the cellular level, Rg3 significantly inhibited free fatty acid (FFA)-induced lipid accumulation, apoptosis and inflammatory factors in primary mouse hepatocytes. The PPARγ overexpression counteracted the inhibitory effect of Rg3 on hepatocyte apoptosis, and increased miR103-3p expression (p < 0.05). Conclusion: These data suggest that Rg3 mitigates NAFLD through regulation of the PPARγ/miR-103- 3p pathway. Therefore, Rg3 may be suitable for the treatment of NAFLD. However, clinical trials are required to ascertain the validity of this therapeutic strategy in clinical practice.