Effects of Fisetin on Allergic Contact Dermatitis via Regulating the Balance of Th17/Treg in Mice

Abstract

Background. Allergic contact dermatitis (ACD) is a form of chronic cutaneous inflammatory disease of immunological origin that has adverse impacts on patient quality of life, underscoring the need for the development of safe and effective therapeutic agents to treat affected individuals. Fisetin is a Chinese herbal preparation that reportedly exhibits antitumor, antioxidant, antimicrobial, anticoagulatory, and antimalarial activity. In the current report, the immunomodulatory activity of fisetin was appraised by assessing its impact on balance between regulatory T (Treg) and Th17 cells in an ACD model. Methods. BALB/c mice ( $n=60$ ) were randomized into control, ACD model, CTX positive control (20 mg/kg), and fisetin treatment groups (three dose levels: 2, 4, or 8 mg/kg). ACD induction was achieved by sensitizing mice on the shaved ventral abdomen via the application of 5% DNFB (50 μL) on days 1 and 2, followed by rechallenge in the right ear with 5% DNFB (20 μL) on day 5. Beginning on day 1, immunized mice were intraperitoneally injected with the appropriate fisetin dose (in saline) once per day for 7 days. On day 7, ear swelling, transcription factor expression, Th17/Treg cell populations, and cytokine production were assessed in vivo. Results. Fisetin treatment significantly suppressed ear swelling and associated inflammatory cell infiltration, besides reducing the production of Th17 cytokines (IL-17, TNF-α, and IL-6) and the expression of the Th17 lineage transcription factor RORγt while simultaneously enhancing Treg-specific cytokine production (TGF-β and IL-10) and the expression of the Treg lineage transcription factor Foxp3, thereby restoring the Th17/Treg cell in ACD mice. Conclusions. These data indicate that fisetin exhibits immunomodulatory activity and can alter the Th17/Treg cell balance, highlighting its potential value as a treatment drug for ACD.