Ginkgo biloba Extract Attenuates the Disruption of Pro- and Anti-inflammatory Balance of Peripheral Blood in Arsenism Patients by Decreasing Hypermethylation of the Foxp3 Promoter Region.

Abstract

Coal-burning type of arsenism, a chronic arsenism caused by environmental arsenic pollution, found firstly at Guizhou Province of China, manifested as the disruption of pro- and anti-inflammatory T cell balance and multiple organ damage, while no specific treatment for the arsenism patients. The effect of methylation of the forkhead box P3 (Foxp3) promoter region on arsenic-induced disruption of pro- and anti-inflammatory T cell balance was first evaluated in this study, between the control and arsenism groups. The results show that arsenic can induce the hypermethylation of 6 sites in the Foxp3 promoter by upregulating the expression of recombinant DNA Methyltransferase 1 (Dnmt1) mRNA, leading to the downregulation of Foxp3 mRNA, Tregs, and interleukin 10 (IL-10, anti-inflammatory cytokine) levels, and increased the levels of interleukin 17 (IL-17, pro-inflammatory cytokine) in the peripheral blood of patients with arsenic poisoning. Further randomized controlled double-blind experiments (including the placebo control groups and the Ginkgo biloba extract (GBE) intervention groups) showed that compared to the placebo control group or before GBE intervention, the levels of Dnmt1 mRNA, Foxp3 methylation, and IL-17 in the peripheral blood of the GBE intervention group were significantly decreased after intervention (P < 0.05), but the levels of regulatory T cells (Tregs) and IL-10 were significantly increased (P < 0.05). Our study provides some limited evidence that GBE can attenuate the disruption of pro- and anti-inflammatory balance of peripheral blood in arsenism patients by decreasing hypermethylation of the Foxp3 promoter region. This study provides scientific basis for further understanding a possible natural medicinal plant, GBE, as a more effective measure to prevent and control the disruption of pro- and anti-inflammatory balance caused by coal-burning type of arsenism.