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

Abstract

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 1,000 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.

Antioxidant and Anti-inflammatory Properties Mediate the Neuroprotective Effects of Hydro-ethanolic Extract of Tiliacora triandra Against Cisplatin-induced Neurotoxicity

“… 50 , 51 Weerawatanakorn et al and Pasachan et al identified the presence of a high content of phenolic constituents in T. triandra leaves extract and these compounds were adjudged as the active principles showing antioxidant, anti-inflammatory and antidiabetic effects in their study. 48 , 52 Our UHPLC-DAD-ESI-QTOF-MS analysis of TT extract indicated the presence of phenolic and flavonoids, which may have accounted for the excellent antioxidant and anti-inflammatory effects against CDDP induced neurotoxicity. For instance Liu et al reported that isovitexin protected against CDDP induced renal injury via anti-inflammatory and antioxidative properties.…”

Application of Quercetin in the Treatment of Gastrointestinal Cancers

“…They investigated the underlying mechanism and the in vivo effects in a type 2 diabetes mellitus (T2DM) rat model. They asked whether TTE could act as a nutritional agent in the management of T2DM and prevent complications such as non-alcoholic steatohepatitis, non-alcoholic fatty liver disease, and eventual cirrhosis ( Pasachan et al, 2021a ). They used a Diels aqueous extract of TTE to affect glucose synthesis in cells with T2DM and HepG2 cells.…”

“…Similar to metformin, TTE showed antidiabetic, anti-triglyceridemic, anti-hyperglycemic, and antioxidant effects in rats with T2DM. TTE may be used as a nutraceutical agent in individuals with insulin resistance, obesity, or those receiving antidiabetic medication ( Pasachan et al, 2021a ). Table 5 lists some studies on the therapeutic effects of quercetin in HCC.…”

Tiliacora triandra Leaf Powder Ethanolic Extract in Combination with Cisplatin or Gemcitabine Synergistically Inhibits the Growth of Cholangiocarcinoma Cells In Vitro and in Nude Mouse Xenograft Models

“…T. triandra is used not only as food but also as traditional medicine. For example, it has been reported as an antipyretic, detoxication agent, anti-inflammatory agent [ 20 ], antimalarial agent [ 21 ], antimycobacterial agent [ 22 ], antioxidant [ 23 ], antidiabetic agent [ 24 ], and anticancer agent [ 25 , 26 ]. Several compounds identified in T. triandra include alkaloids [ 25 ], phenolic compounds [ 23 , 27 ], flavonoids, polysaccharides [ 27 ], and fatty acids [ 26 ].…”