Department of Geriatrics, The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology, Kunming, Yunnan 650100, P.R. China.
Department of Pathophysiology, Medical School, Kunming University of Science and Technology, Kunming, Yunnan 650500, P.R. China.
Mol Med Rep. 2022 May;25(5). doi: 10.3892/mmr.2022.12694. Epub 2022 Mar 24.
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 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.
非酒精性脂肪性肝病 (NAFLD) 的发病率很高，在严重情况下可导致肝硬化甚至肝细胞癌。据我们所知，目前尚无安全有效的方法来治疗这种疾病。人参皂苷 Rg1（Rg1）是从人参和三七中提取的一种活性单体。本研究采用中长链脂肪乳剂处理 HHL-5 肝细胞，建立 NAFLD 细胞模型，观察 Rg1 对 HHL-5 肝细胞脂肪堆积、凋亡及凋亡相关蛋白表达水平的影响。结果表明，Rg1 抑制 HHL-5 细胞脂肪堆积，同时抑制细胞凋亡，下调促凋亡蛋白 Bax 的表达水平，上调抗凋亡蛋白 Bcl-2 的表达水平，表明 Rg1 可通过调节 Bcl-2 家族蛋白促进线粒体的稳定性或完整性，发挥抗凋亡作用。此外，Rg1 显著下调脂肪变性 HHL-5 细胞中鞘氨醇信号通路关键酶鞘氨醇-1-磷酸酶 1（SGPL1）的表达水平，并增加下游存活信号磷酸化（p）Akt 和 p-Erk1/2 的表达水平。此外，过表达 SGPL1 可消除 Rg1 对 SGPL1 过表达脂肪变性 HHL-5 细胞的抗凋亡作用，并下调 Bcl-2、p-Akt 和 p-Erk1/2 等存活蛋白的表达水平，而促凋亡 Bax 的表达水平则显著增加。综上所述，虽然有一些关于 Rg1 对脂肪性肝细胞保护作用的报道，但据我们所知，本研究首次报道 Rg1 可能通过调节鞘氨醇信号通路中的 SGPL1 发挥抗脂肪性肝细胞凋亡作用。Rg1 是中国药物血塞通的主要成分；因此，本研究结果可能为 Rg1 或血塞通治疗非酒精性脂肪性肝病患者提供理论分子基础。
