Santos, P.R.; Danetti, S.; Rastegar, A.J.; de Souza, W.V.; Frassini, R.; Scariot, F.J.; Moura, S.; Roesch-Ely, M. Hydroxyhydroquinone and Quassinoids as Promising Compounds with Hypoglycemic Activity through Redox Balance. Compounds2024, 4, 17-36.
Santos, P.R.; Danetti, S.; Rastegar, A.J.; de Souza, W.V.; Frassini, R.; Scariot, F.J.; Moura, S.; Roesch-Ely, M. Hydroxyhydroquinone and Quassinoids as Promising Compounds with Hypoglycemic Activity through Redox Balance. Compounds 2024, 4, 17-36.
Santos, P.R.; Danetti, S.; Rastegar, A.J.; de Souza, W.V.; Frassini, R.; Scariot, F.J.; Moura, S.; Roesch-Ely, M. Hydroxyhydroquinone and Quassinoids as Promising Compounds with Hypoglycemic Activity through Redox Balance. Compounds2024, 4, 17-36.
Santos, P.R.; Danetti, S.; Rastegar, A.J.; de Souza, W.V.; Frassini, R.; Scariot, F.J.; Moura, S.; Roesch-Ely, M. Hydroxyhydroquinone and Quassinoids as Promising Compounds with Hypoglycemic Activity through Redox Balance. Compounds 2024, 4, 17-36.
Abstract
Reactive oxygen species (ROS) are essential signaling molecules involved in almost all metabolic processes. In the present study, a HepG2 insulin resistant cell model (HepG2/IRM) was chosen to investigate the efficacy of hydroxyhydroquinone (HHQ), quassinoids from Picrasma crenata and flavonoids from Rourea cuspidata as potential glycemic controlling agents for insulin sensitization. HHQ was synthetized and extracts from P. crenata and R. cuspidata were tested in hepatic cell line, which were evaluated through cytotoxic activity, levels of ROS, ATP, mitochondrial membrane potential and expression of FoxO1 protein in a high glucose environment. Our results demonstrate that the HHQ, quassinoids and flavonoids were not toxic to cells at concentrations up to 50mM and 50 mg/mL in HepG2/IRM and HepG2. ROS activity was increased for all groups with insulin induction upon glucose consumption. HHQ and quassinoids downregulate the expression of FoxO1 in comparison to cells exposed to flavonoids. The results here presented suggests that quassinoids may act on nuclear glucocorticoid receptors to inhibit FoxO1 expression by competing with cortisol and HHQ can act as ROS scavenger to ameliorate mitochondria activity and modulate ATP generation. 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.
Keywords
hydroxyhydroquinone; quassinoids; glycemia
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
