Cinnamomum verum (Syn. C. zeylanicum) bark ethanolic extract inhibits carbohydrate digestive enzymes and enhances glucose uptake in 3T3-adipocytes: Insights from in vitro and computational perspectives

Abstract

Diabetes is a burdensome global disease that increases the risks of other vascular health complications and constantly contributing to global mortality rate. Over the years, medicinal plants have come in handy for the treatment and management of the disease. The present study was aimed at investigating the possible anti-diabetic activity of ethanolic extract of C. verum's bark using in vitro and in silico models. The total phenolic and flavonoid contents of C. verum was determined as well as the quantification of polyphenolic compounds by high-performance liquid chromatography (HPLC). The inhibitory effect of C. verum on the carbohydrate digestive enzymes, α-glucosidase and α-amylase were elucidated as well as its effect on 3T3 adipocytes glucose uptake. HPLC-quantified compounds were docked with GLUT 4 glucose transporter and peroxisome proliferator-activated receptor-γ (PPAR-γ). C. verum extract displayed a considerable level of phenolic and flavonoid contents, 223.69 ± 0.23 mg GAE/g and 5.03 ± 0.44 mg QE/g, respectively and significantly (p < 0.05) inhibited α-glucosidase (IC₅₀: 59.94 µg/mL) and α-amylase (IC₅₀: 222.16 µg/mL) enzymes, while promoting adipocyte glucose uptake. Strong binding affinity was recorded in the docking of the HPLC-quantified compounds (gallic acid, quercetin, vanillic acid and ferulic acid) of C. verum ethanolic bark extract with GLUT 4 and PPAR-γ. The extract was not cytotoxic to 3T3-L1 fibroblast cell lines exposed for over 48 hrs. The results portray C. verum’s bark ethanolic extract as a potential target for glycemic control by its demonstrated α-glucosidase and α-amylase inhibitory properties, which can be attributed to its phyto-constituents. Future in vivo studies, supported by molecular analysis are recommended to corroborate these results.