Department of Physiology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Division of Physiology, School of Medical Sciences, University of Phayao, Phayao 56000, Thailand.
Molecules. 2021 Feb 25;26(5):1239. doi: 10.3390/molecules26051239.
This study investigated the effects of (Colebr.) Diels aqueous extract (TTE) on hepatic glucose production in hepatocellular carcinoma (HepG2) cells and type 2 diabetic (T2DM) conditions. HepG2 cells were pretreated with TTE and its major constituents found in TTE, epicatechin (EC) and quercetin (QC). The hepatic glucose production was determined. The in vitro data were confirmed in T2DM rats, which were supplemented daily with 1000 mg/kg body weight (BW) TTE, 30 mg/kg BW metformin or TTE combined with metformin for 12 weeks. Results demonstrate that TTE induced copper-zinc superoxide dismutase, glutathione peroxidase and catalase genes, similarly to EC and QC. TTE decreased hepatic glucose production by downregulating phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and increasing protein kinase B and AMP-activated protein kinase phosphorylation in HepG2 cells. These results correlated with the antihyperglycemic, antitriglyceridemic, anti-insulin resistance, and antioxidant activities of TTE in T2DM rats, similar to the metformin and combination treatments. Consistently, impairment of hepatic gluconeogenesis in T2DM rats was restored after single and combined treatments by reducing PEPCK and G6Pase genes. Collectively, TTE could potentially be developed as a nutraceutical product to prevent glucose overproduction in patients with obesity, insulin resistance, and diabetes who are being treated with antidiabetic drugs.
本研究探讨了（Colebr.）Diels 水提取物（TTE）对肝癌（HepG2）细胞和 2 型糖尿病（T2DM）状态下肝葡萄糖生成的影响。用 TTE 及其在 TTE 中发现的主要成分表儿茶素（EC）和槲皮素（QC）预处理 HepG2 细胞。测定肝葡萄糖生成。在 T2DM 大鼠中验证了体外数据，这些大鼠每天补充 1000mg/kg 体重（BW）TTE、30mg/kg BW 二甲双胍或 TTE 与二甲双胍联合补充 12 周。结果表明，TTE 诱导铜锌超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶基因，与 EC 和 QC 相似。TTE 通过下调磷酸烯醇丙酮酸羧激酶（PEPCK）和葡萄糖-6-磷酸酶（G6Pase）并增加 HepG2 细胞中蛋白激酶 B 和 AMP 激活蛋白激酶的磷酸化来降低肝葡萄糖生成。这些结果与 T2DM 大鼠中 TTE 的降血糖、降甘油三酯、抗胰岛素抵抗和抗氧化活性相关，与二甲双胍和联合治疗相似。同样，在单一和联合治疗后，T2DM 大鼠的肝糖异生受损得到恢复，这是通过降低 PEPCK 和 G6Pase 基因实现的。总之，TTE 有可能被开发为一种营养保健品，以预防肥胖、胰岛素抵抗和糖尿病患者在接受抗糖尿病药物治疗时的葡萄糖过度产生。
