Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, South Korea.
J Ethnopharmacol. 2020 Sep 15;259:112927. doi: 10.1016/j.jep.2020.112927. Epub 2020 May 7.
Ginsenoside, a major pharmacologically active ingredient in ginseng, has been known to exhibit beneficial properties such as antioxidant and anti-inflammatory effects. Ginsenoside compound Mc1 is one of the newly identified de-glycosylated ginsenosides. Endoplasmic reticulum (ER) stress has implicated in the development of non-alcoholic fatty liver disease (NAFLD) through apoptosis and lipid accumulation.
We aimed to examine the protective effects of Mc1 treatment on ER stress-induced cell death and impaired insulin signaling in HepG2 human hepatoblastoma cells and ER stress-induced liver steatosis and insulin resistance in a diet-induced obesity (DIO) mouse model.
HepG2 cells were treated with palmitate and Mc1 to evaluate the effects of Mc1 on ER stress-induced damage. C57BL/6 mice were fed with a high-fat diet (HFD) for 4 weeks and received an intraperitoneal injection of either vehicle or Mc1 (10 mg/kg/day). The control mice were fed with a chow diet and injected with vehicle for the same period. ER stress, cell death, and degree of steatosis were evaluated in the liver tissues of mice. The effect of Mc1 treatment on glucose metabolism was also determined.
Mc1 co-treatment reduced the palmitate-induced ER stress and death of HepG2 cells. The palmitate-induced insulin resistance improved after Mc1 co-treatment. Consistent with the in vitro data, chronic Mc1 supplementation reduced ER stress and apoptotic damage in the liver of obese mice. Mc1 treatment ameliorated glucose intolerance and insulin resistance through the suppression of c-Jun N-terminal kinase (JNK) phosphorylation. In addition, Mc1 treatment reduced obesity-induced lipogenesis and prevented fat accumulation in the liver of DIO mice.
Mc1 exerted protective effects against ER stress-induced apoptotic damage, insulin resistance and lipogenesis in palmitate-treated hepatocytes and in the liver of DIO mice. Therefore, Mc1 supplementation could be a potential therapeutic strategy to prevent NAFLD in patients with obesity and insulin resistance.
人参中的主要药理活性成分——人参皂苷，已被证明具有抗氧化和抗炎等有益特性。人参皂苷 Mc1 是新鉴定的去糖基化人参皂苷之一。内质网（ER）应激通过细胞凋亡和脂质积累参与非酒精性脂肪性肝病（NAFLD）的发展。
我们旨在研究 Mc1 处理对 ER 应激诱导的 HepG2 人肝癌细胞死亡和胰岛素信号受损的保护作用，以及 Mc1 处理对饮食诱导肥胖（DIO）小鼠模型中 ER 应激诱导的肝脂肪变性和胰岛素抵抗的影响。
用棕榈酸和 Mc1 处理 HepG2 细胞，以评估 Mc1 对 ER 应激诱导损伤的影响。C57BL/6 小鼠用高脂肪饮食（HFD）喂养 4 周，并接受 Mc1（10mg/kg/天）或载体的腹腔注射。对照组小鼠用标准饮食喂养，并在相同时间内注射载体。评估小鼠肝脏中的 ER 应激、细胞死亡和脂肪变性程度。还测定了 Mc1 处理对葡萄糖代谢的影响。
Mc1 共处理可降低棕榈酸诱导的 HepG2 细胞 ER 应激和死亡。Mc1 共处理改善了棕榈酸诱导的胰岛素抵抗。与体外数据一致，慢性 Mc1 补充可减少肥胖小鼠肝脏中的 ER 应激和凋亡损伤。Mc1 治疗通过抑制 c-Jun N 末端激酶（JNK）磷酸化改善葡萄糖不耐受和胰岛素抵抗。此外，Mc1 处理可减少肥胖引起的脂肪生成并防止 DIO 小鼠肝脏脂肪堆积。
Mc1 对棕榈酸处理的肝细胞和 DIO 小鼠肝脏中的 ER 应激诱导的细胞凋亡损伤、胰岛素抵抗和脂肪生成具有保护作用。因此，Mc1 补充可能是预防肥胖和胰岛素抵抗患者 NAFLD 的一种潜在治疗策略。
