Ginkgo biloba extract attenuates the disruption of pro-and anti-inflammatory T-cell balance in peripheral blood of arsenicosis patients

Abstract

Endemic arsenicosis is a public health problem that affects thousands of people worldwide. However, the biological mechanism involved is not well characterized, and there is no specific treatment. Exposure to arsenic may be associated with immune-related problems. In the present work, we performed an investigation to determine whether the Th17/Treg balance was abnormal in peripheral blood mononuclear cells (PBMCs) of patients with arsenicosis caused by burning coal. Furthermore, we investigated the effect of Ginkgo biloba extract (GBE) on the Th17/Treg imbalance in patients with arsenicosis. In this trial, 81 arsenicosis patients and 37 controls were enrolled. The numbers of Th17 and Treg cells, as well as related transcription factors and serum cytokines, were determined at the beginning and end of the study. Patients with arsenicosis exhibited higher levels of Th17 cells, Th17-related cytokines (IL-17A and IL-6), and the transcription factor RORγt. There were lower levels of Treg cells, a Treg-related cytokine (IL-10), and the transcription factor Foxp3 as compared with controls. There was a positive correlation between the levels of Th17 cells and IL-17A and the levels of arsenic in hair. Arsenicosis patients were randomly assigned to a GBE treatment group or a placebo group. After 3 months of follow-up, 74 patients completed the study (39 cases in the GBE group and 35 in the placebo group). Administration of GBE to patient upregulated the numbers of Treg cells and the level of IL-10 and downregulated the numbers of Th17 cells and the levels of cytokines associated with Th17 cells. The mRNA levels of Foxp3 and RORγt were increased and decreased, respectively. These results indicated that exposure to arsenic is associated with immune-related problems. The present investigation describes a previously unknown mechanism showing that an imbalance of pro-and anti-inflammatory T cells is involved in the pathogenesis of arsenicosis and that a GBE exerts effects on arsenicosis through regulation of the pro-and anti-inflammatory T cell balance.

Imbalanced inflammatory response in subchronic arsenic‐induced liver injury and the protective effects of Ginkgo biloba extract in rats: Potential role of cytokines mediated cell–cell interactions

“…While, the ratio of Th17 to Treg cells in the 10 mg/kg NaAsO 2 was significantly increased by 164% compared to the baseline (Figure 2(D–F)). Combine with our previous study 15 that As exposure significantly disrupted the balance of Th17 and Treg cells as well as the corresponding cytokines IL‐17, IL‐6, and IL‐10 suggested that prolonged arsenic exposure might exhaust the immunoregulatory capacity of Treg subpopulations, ultimately resulting in Th17 predominant effects and disrupting the balance of pro‐inflammatory and anti‐inflammatory. Recent literature has indicated that the imbalance of Th17 and Treg cells is involved in the liver disease 12 .…”

“…Furthermore, overexpression pro‐inflammatory mediators of TNF‐α and IL‐6 was also observed in chronic arsenic exposure individuals 47 . Our previous study also found that pro‐inflammatory cytokines IL‐6 and IL‐17A were higher in patients with arsenicosis 15 . In accordance with these observations, the present study showed that the concentration of pro‐inflammatory mediators IL‐6 and IL‐17 in sub‐chronic arsenic‐exposed rat's serum and liver were consistently increased compared with the control group.…”

“…Moreover, increasing evidence indicated that immunological factors play an important role in the pathological process of various liver disease 42 . GBE has performance many physiological benefits and pharmacological effects, such as antioxidant, anti‐inflammatory, and immunomodulatory 15,30,43 . Thus, in this paper, GBE was used as an immunomodulatory agent to investigated its protective effects on As‐induced liver injury.…”

“…Several mechanisms have been proposed for the beneficial effects of GBE , including anti‐oxidation, 26 anti‐inflammatory, 27 and immunoregulatory 28 . In a recent study, we present a scientific evidence indicated that GBE treatment can ameliorate arsenicosis patients immunological dysfunction by regulating the balance of inflammatory response 15 . Furthermore, some studies have found that GBE intervention showed a protective effect on inflammatory‐related liver damage 29–31 .…”

“…Existing studies indicated that Th17 and Treg cells represent two aspects of immune response and the subtle balance of Th17 and Treg cells is vital in the maintenance of liver immune homeostasis 12 . Our previous research found that the skewed balance of Th17 and Treg cells was closely associated with the pathogenesis of arsenicosis, 15 and investigation in arsenic poisoning rats further revealed that arsenic‐induced imbalanced immune responses was involved in arsenic‐induced liver damage 16,17 . Although the correlations between arsenic induced immunotoxicity and liver damage have been explored to some extent, the molecular mechanism underlying remains unclear.…”