Background

Ginsenoside F2 (GF2), a minor component of Panax ginseng, has been reported to possess a wide variety of pharmacological activities. However, its effects on glucose metabolism have not yet been reported. Here, we investigated the underlying signaling pathways involved in its effects on hepatic glucose.

Methods

HepG2 cells were used to establish insulin-resistant (IR) model and treated with GF2. Cell viability and glucose uptake-related genes were also examined by real-time PCR and immunoblots.

Results

Cell viability assays showed that GF2 up to 50 μM did not affect normal and IR-HepG2 cell viability. GF2 reduced oxidative stress by inhibiting phosphorylation of the mitogen-activated protein kinases (MAPK) signaling components such as c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2), and p38 MAPK, and reducing the nuclear translocation of NF-κB. Furthermore, GF2 activated PI3K/AKT signaling, upregulated the levels of glucose transporter 2 (GLUT-2) and GLUT-4 in IR-HepG2 cells, and promoted glucose absorption. At the same time, GF2 reduced phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression as well as inhibiting gluconeogenesis.

Conclusion

Overall, GF2 improved glucose metabolism disorders by reducing cellular oxidative stress in IR-HepG2 cells via MAPK signaling, participating in the PI3K/AKT/GSK-3β signaling pathway, promoting glycogen synthesis, and inhibiting gluconeogenesis.

中文翻译：

---

人参皂苷 F2 通过调节人肝癌细胞胰岛素信号转导增强葡萄糖代谢

背景

人参皂甙 F2 (GF2) 是人参的次要成分，据报道具有多种药理活性。然而，其对葡萄糖代谢的影响尚未见报道。在这里，我们调查了涉及其对肝葡萄糖影响的潜在信号通路。

方法

HepG2 细胞用于建立胰岛素抵抗 (IR) 模型并用 GF2 处理。还通过实时 PCR 和免疫印迹检查了细胞活力和葡萄糖摄取相关基因。

结果

细胞活力测定显示高达 50 μM 的 GF2 不影响正常和 IR-HepG2 细胞活力。GF2 通过抑制有丝分裂原活化蛋白激酶 (MAPK) 信号成分（如 c-Jun N 末端激酶 (JNK)、细胞外信号调节激酶 1/2 (ERK1/2) 和 p38 MAPK）的磷酸化来减少氧化应激，减少 NF-κB 的核转位。此外，GF2 激活 PI3K/AKT 信号，上调 IR-HepG2 细胞中葡萄糖转运蛋白 2 (GLUT-2) 和 GLUT-4 的水平，并促进葡萄糖吸收。同时，GF2 降低磷酸烯醇丙酮酸羧激酶和葡萄糖-6-磷酸酶的表达并抑制糖异生。

结论

总体而言，GF2通过MAPK信号降低IR-HepG2细胞的细胞氧化应激，参与PI3K/AKT/GSK-3β信号通路，促进糖原合成，抑制糖异生，从而改善糖代谢紊乱。