Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Graduate Institute of Health Industry Technology, Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Taoyuan City, Taiwan.
Kaohsiung J Med Sci. 2024 Mar;40(3):280-290. doi: 10.1002/kjm2.12795. Epub 2024 Jan 31.
Gypenoside XIII is isolated from Gynostemma pentaphyllum (Thunb.) Makino. In mice, G. pentaphyllum extract and gypenoside LXXV have been shown to improve non-alcoholic steatohepatitis (NASH). This study investigated whether gypenoside XIII can regulate lipid accumulation in fatty liver cells or attenuate NASH in mice. We used HepG2 hepatocytes to establish a fatty liver cell model using 0.5 mM oleic acid. Fatty liver cells were treated with different concentrations of gypenoside XIII to evaluate the molecular mechanisms of lipid metabolism. In addition, a methionine/choline-deficient diet induced NASH in C57BL/6 mice, which were given 10 mg/kg gypenoside XIII by intraperitoneal injection. In fatty liver cells, gypenoside XIII effectively suppressed lipid accumulation and lipid peroxidation. Furthermore, gypenoside XIII significantly increased SIRT1 and AMPK phosphorylation to decrease acetyl-CoA carboxylase phosphorylation, reducing fatty acid synthesis activity. Gypenoside XIII also decreased lipogenesis by suppressing sterol regulatory element-binding protein 1c and fatty acid synthase production. Gypenoside XIII also increased lipolysis and fatty acid β-oxidation by promoting adipose triglyceride lipase and carnitine palmitoyltransferase 1, respectively. In an animal model of NASH, gypenoside XIII effectively decreased the lipid vacuole size and number and reduced liver fibrosis and inflammation. These findings suggest that gypenoside XIII can regulate lipid metabolism in fatty liver cells and improve liver fibrosis in NASH mice. Therefore, gypenoside XIII has potential as a novel agent for the treatment of NASH.
绞股蓝皂苷 XIII 从绞股蓝（Thunb.）Makino 中分离得到。在小鼠中，已证实绞股蓝提取物和绞股蓝皂苷 LXXV 可改善非酒精性脂肪性肝炎（NASH）。本研究旨在探讨绞股蓝皂苷 XIII 是否可调节脂肪肝细胞中的脂质积累或减轻 NASH 小鼠的肝脏损伤。我们使用 HepG2 肝细胞，通过添加 0.5 mM 油酸建立脂肪肝细胞模型。用不同浓度的绞股蓝皂苷 XIII 处理脂肪肝细胞，以评估脂质代谢的分子机制。此外，采用蛋氨酸/胆碱缺乏饮食诱导 C57BL/6 小鼠 NASH，并用腹腔注射 10 mg/kg 的绞股蓝皂苷 XIII 进行治疗。在脂肪肝细胞中，绞股蓝皂苷 XIII 可有效抑制脂质积累和脂质过氧化。此外，绞股蓝皂苷 XIII 可显著增加 SIRT1 和 AMPK 磷酸化，减少乙酰辅酶 A 羧化酶磷酸化，降低脂肪酸合成活性。绞股蓝皂苷 XIII 还可通过抑制固醇调节元件结合蛋白 1c 和脂肪酸合酶的产生来减少脂生成。绞股蓝皂苷 XIII 还可通过分别促进脂肪甘油三酯脂肪酶和肉碱棕榈酰基转移酶 1 来增加脂肪分解和脂肪酸 β-氧化。在 NASH 动物模型中，绞股蓝皂苷 XIII 可有效减少肝脂肪变性细胞的脂质空泡大小和数量，并减轻肝纤维化和炎症。这些发现表明，绞股蓝皂苷 XIII 可调节脂肪肝细胞中的脂质代谢并改善 NASH 小鼠的肝纤维化。因此，绞股蓝皂苷 XIII 可能成为治疗 NASH 的新型药物。
