4.6 Article

Tiliacora triandra (Colebr.) Diels Leaf Aqueous Extract Inhibits Hepatic Glucose Production in HepG2 Cells and Type 2 Diabetic Rats

Journal

MOLECULES
Volume 26, Issue 5, Pages -

Publisher

MDPI
DOI: 10.3390/molecules26051239

Keywords

Tiliacora triandra (Colebr; ) Diels; diabetes; hepatic insulin resistance; hepatic gluconeogenesis; antioxidant

Funding

  1. Faculty of Medicine Research Fund, Chiang Mai University, Chiang Mai, Thailand [66/2560, 93/2560]
  2. Thailand Research Fund [PHD58I0009, RSA5980009]
  3. NSTDA Chair Professor grant of the Crown Property Bureau Foundation
  4. National Science and Technology Development Agency

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The study showed that Tiliacora triandra aqueous extract could reduce hepatic glucose production and enhance antioxidant capacity in HepG2 cells and T2DM rats. It also improved insulin resistance and regulated key gene expressions related to glucose metabolism. These findings suggest the potential use of TTE as a nutraceutical product for diabetes management.
This study investigated the effects of Tiliacora triandra (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.

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