Cytoprotective and Anti-genotoxic Effects of Xanthone Derivatives from Garcinia mangostana Against H2O2 Induced PBMC Cell and Blood Leukocytes Damage of Normal and Type 2 Diabetes Volunteers

Abstract

Hyperglycemia is well-known for inducing cellular oxidative damage in type II diabetes (T2D) patients. This research addressed the cytoprotective and anti-genotoxic effect of xanthone derivatives from Garcinia mangostana against hydrogen peroxide (H2O2)-induced human peripheral blood mononuclear cell (PBMC) and blood leukocytes damage of the normal and T2D volunteers. The cytoprotective effects of an aqueous extract of xanthone (100 and 200 µg/mL) was assessed on cell viability and free radical scavenging activity using the trypan blue exclusion method on PBMC cells. Malondialdehyde (MDA) levels and lactate dehydrogenase (LDH) activity were measured as cellular oxidative damage markers and estimated from culture medium of PBMCs of normal and T2D volunteers. The anti-genotoxicity was assessed as the protective effect of xanthone against H2O2-induce DNA damage of blood leukocytes of the normal volunteers following comet assay technique. Xanthone and Gallic acid (control) concentrations 100, 200 and 100 µg/mL significantly (P < 0.05) protected from H2O2 (20 mM)-induced oxidative damage of PBMCs. It was confirmed by increased cell viability and free radical scavenging activity coupled with the decreased MDA and LDH levels in cell culture medium compared to H2O2 (20 mM)-treated group. In H2O2 (40 mM)-induced blood leukocytes of normal volunteers, different concentration xanthone (50 - 500 µg/mL) significantly (P < 0.05) improved the anti-genotoxicity effect compared to negative/positive control group by lowering comet formation. Xanthone treatments on PBMCs and blood leukocytes of the normal and T2D volunteers could attenuate the H2O2-induced cellular oxidative damage and cell death via exhibiting antioxidant and free radical scavenging activities.