Disease Prevention and Health Management Center, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, China.
Disease Prevention and Health Management Center, People's Hospital of Songyang, Lishui, China.
Pharm Biol. 2022 Dec;60(1):1949-1959. doi: 10.1080/13880209.2022.2126503.
Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disease, can develop into metabolic associated fatty liver disease (MAFLD). Gypenosides (GP), the main phytochemical component of (Thunb.) Makino (Cucurbitaceae), have been applied for treatment of metabolic diseases.
We investigate how GP modulate MAFLD-related hepatic steatosis and intestinal barrier injury.
In cell experiments, Caco-2 cells were treated with GP (150 or 200 μmol/L, 24 h), following lipopolysaccharide (LPS) exposure (10 μg/mL, 24 h) to mimic MAFLD . In experiments, control, model and model + GP groups were set. High fructose diet/high fat (HFD/HF)-fed (12 weeks) MAFLD rats received GP treatment (300 mg/kg, 6 weeks), followed by intra-peritoneal glucose tolerance test and histopathological examination of rat liver and intestinal mucosa using haematoxylin-eosin staining.
GP at 200 μM significantly reversed LPS-induced decreases in transepithelial electrical resistance (TER) value (25%), protein expression of occludin (two fold) and ZO-1 (four fold), and the ratio of p-AMPK to AMPK (five fold), while partially repressing LPS-induced leakage of FD4 (50%) and LPS-induced increases in the Toll-like receptor 4 (TLR4) level (50%) and the ratio of p-p65 to p65 (55%). Compared with the model rats, rats with GP treatment presented a reduction in gain of weight and glucose tolerance. In addition, GP alleviated HFD/HF-induced histopathological abnormalities in rat liver and intestinal mucosa.
GP attenuates hepatic steatosis and intestinal barrier injury in MAFLD rats via the AMPK and TLR4/nuclear factor kappa B (NF-κB) pathways, providing a potential treatment for MAFLD patients.
非酒精性脂肪性肝病（NAFLD）是最常见的慢性肝病，可发展为代谢相关脂肪性肝病（MAFLD）。绞股蓝总苷（GP）是葫芦科绞股蓝（Thunb.）Makino 的主要植物化学成分，已被用于治疗代谢性疾病。
研究 GP 如何调节 MAFLD 相关的肝脂肪变性和肠道屏障损伤。
在细胞实验中，用 GP（150 或 200 μmol/L，24 h）处理 Caco-2 细胞，然后用脂多糖（LPS，10 μg/mL，24 h）处理以模拟 MAFLD。在动物实验中，设置对照组、模型组和模型+GP 组。高脂高果糖饮食（HFD/HF）喂养（12 周）的 MAFLD 大鼠给予 GP 治疗（300 mg/kg，6 周），然后进行腹腔内葡萄糖耐量试验，并通过苏木精-伊红染色对大鼠肝和肠黏膜进行组织病理学检查。
200 μM 的 GP 可显著逆转 LPS 诱导的跨上皮电阻（TER）值（25%）、occludin 蛋白表达（2 倍）和 ZO-1 蛋白表达（4 倍）以及 p-AMPK/AMPK 比值（5 倍）的降低，同时部分抑制 LPS 诱导的 FD4 渗漏（50%）和 LPS 诱导的 Toll 样受体 4（TLR4）水平（50%）和 p-p65/p65 比值（55%）的升高。与模型大鼠相比，给予 GP 治疗的大鼠体重增加和葡萄糖耐量降低。此外，GP 减轻了 HFD/HF 诱导的大鼠肝和肠黏膜的组织病理学异常。
GP 通过 AMPK 和 TLR4/核因子 kappa B（NF-κB）通路减轻 MAFLD 大鼠的肝脂肪变性和肠道屏障损伤，为 MAFLD 患者提供了一种潜在的治疗方法。
