Ginsenoside Rg1 exerts anti-apoptotic effects on non-alcoholic fatty liver cells by downregulating the expression of SGPL1

Non-alcoholic fatty liver disease (NAFLD) has a high incidence, and can lead to liver cirrhosis and even hepatocellular carcinoma in severe cases. To the best of our knowledge, there is currently no safe and effective treatment for the management of this disease. Ginsenoside Rg1 (Rg1) is an active monomer derived from ginseng and notoginseng. In the present study, HHL-5 hepatocytes were used to establish an in vitro cell model of NAFLD by medium- and long-chain fat emulsion treatment, and the effects of Rg1 on adipose accumulation, apoptosis and the expression levels of apoptosis-related proteins in HHL-5 hepatocytes were examined. The results demonstrated that Rg1 inhibited the accumulation of fat in HHL-5 cells, while inhibiting apoptosis, and Rg1 downregulated the expression levels of the pro-apoptotic protein Bax and upregulated the expression levels of the anti-apoptotic protein Bcl-2, indicating that Rg1 could promote the stability or integrity of mitochondria and exert an anti-apoptotic effect by regulating Bcl-2 family proteins. In addition, Rg1 markedly downregulated the expression levels of sphingosine-1-phosphate lyase 1 (SGPL1), a key enzyme in the sphingosine signaling pathway, in HHL-5 cells with steatosis, and increased the expression levels of the downstream pro-survival signals phosphorylated (p-)Akt and p-Erk1/2. Furthermore, overexpression of SGPL1 abolished the anti-apoptotic effect of Rg1 on SGPL1-overexpressing HHL-5 cells with steatosis, and downregulated the expression levels of pro-survival proteins, such as Bcl-2, p-Akt and p-Erk1/2, whereas the expression levels of pro-apoptotic Bax were markedly increased. In conclusion, although there are some reports regarding the protective effect of Rg1 on fatty liver cells, to the best of our knowledge, the present study is the first to report that Rg1 may exert an anti-apoptotic effect on fatty liver cells by regulating SGPL1 in the sphingosine signaling pathway. Rg1 is the main component of the prescription drug Xuesaitong in China; therefore, the findings of the present study may provide a theoretical molecular basis for the use of Rg1 or Xuesaitong in the treatment of patients with NAFLD.