Amelioration of imiquimod induced psoriasis through reduction in IL-17A and Th17 population by dihydromyricetin involves regulation of RORγt pathway.

BACKGROUND AND PURPOSE

Psoriasis is a chronic inflammatory skin disorder affecting approximately 125 million people. IL-17 A secreted from Th17 cells plays a major role in elucidating psoriasis. Dihydromyricetin (DHM) is plant derived flavonoid isolated from leaves and stems of Rattan tea (Ampelopsis grossedentata). Reports indicate anti-inflammatory property of DHM but no information is currently available on its mechanism of action or effect on IL17 producing Th17 cells and exact role in psoriasis.

EXPERIMENTAL APPROACH

DHM shows strong anti-inflammatory properties in vitro, DHM reduced LPS-induced ROS generation, and pro-inflammatory cytokines in macrophages. The efficacy of DHM against chronic inflammatory disorder in vivo was investigated in imiquimod-induced psoriasis established in male BALB/C mice as this model closely resembles human psoriasis. Immunophenotyping and cytokine production were observed by flow cytometry, the status of gene expression was determined by real-time PCR, and nuclear co-localization and immunofluorescence of skin tissue were studied using confocal microscopy.

KEY RESULTS

We observed increased inflammatory parameters in imiquimod treated diseased animals and the application of DHM topically and orally reduced the inflammatory parameters and improved indicators of cardiac damage prominent in psoriatic conditions. In our study, we found that the application of DHM dose-dependently reduced the percentage of IL-17 A-producing T cell population and reduced the nuclear co-translocation of RORγt in psoriatic T cells and possibly also influenced upstream IL-6 signaling.

CONCLUSION AND IMPLICATIONS

Our study suggests that DHM effectively alleviates psoriatic symptoms, and its mechanism of action involves the regulation of RORγt pathway in T cells.