Hydroxyhydroquinone and Quassinoids as Promising Compounds with Hypoglycemic Activity through Redox Balance

In the present study, an insulin-resistant cell model (human hepatocellular carcinoma cell line: HepG2) was chosen to investigate the efficacy of two compound classes and their common molecular motif for glycemic control and insulin sensitization. The two compounds’ classes were flavonoid extracts from Rourea cuspidata and quassinoid extracts from Picrasma crenata. The flavonoid-like hydroxyhydroquinone (HHQ) was synthesized. HepG2 cells were tested in a high-glucose environment (HepG2/IRM) by monitoring ROS activity, the concentration of adenosine triphosphate (ATP), and the measurement of mitochondrial membrane potential (MMP). The expression of forkhead box O1 (FOXO1) protein, which mediates gluconeogenesis and insulin resistance, was also investigated using indirect immunocytochemistry and Western blot techniques. A significant increase in glucose uptake and well-regulated ATP concentrations were observed in the treated cells. The downregulation of FOXO1 expression was seen in cells treated with HHQ and quassinoids in comparison to cells treated with flavonoids. This study provides a pharmacological basis for the application of HHQ, quassinoids from P. crenata, and flavonoids from R. cuspidata in the treatment of metabolic diseases such as type 2 diabetes mellitus.