Dihydromyricetin, the active component of rattan tea alleviates symptoms of systemic sclerosis and atopic dermatitis through modulation of RORγt and IL17A production in T cells

Abstract

Systemic sclerosis is a chronic inflammatory disease affecting the connective tissue of the human body by inducing fibrosis mainly in skin and lungs. Atopic dermatitis is another chronic inflammatory skin diseases that affects one-fifth of the population in developed countries. Dysregulation of the immune cells are one of the major characteristic features behind establishment of these two diseases. Several medicines are used to treat these diseases, but they have several side effects and high production cost. Low side effect and easy availability has generated renewed interest in studying plant derived medicines. Dihydromyricetin (Ampelopsin), a flavonoid compound extracted from stem and leaves of Ampelopsis grossedentata has shown potent anti-inflammatory property in vitro. In this study, bleomycin induced scleroderma and oxazolone induced dermatitis model were established in male BALB/c mice to check the in vivo efficacy of dihydromyricetin. Immunophenotyping and cytokine production were investigated by flow cytometry; immunofluorescence of skin was studied using confocal microscopy. We observed oral application of dihydromyricetin significantly reduced the inflammatory parameters in both diseases. We also found that dihydromyricetin dose dependently reduced the percentage of IL17A producing T cell population and reduced the total expression of RORγt in diseased T cells. Furthermore, we also found stable and strong binding of dihydromyricetin- RORγt protein complex. Stability of protein-ligand complex was examined by MD simulation study. We suggest that dihydromyricetin alleviates scleroderma and dermatitis symptoms by regulating the RORγt pathway.