Nitazoxanide and Umbelliferone improves Imiquimod-induced psoriasis in Balb/C mice

Abstract

Signal Transducer and Activator of Transcription (STAT) 3 is a significant contributor to the development and pathogenesis of psoriasis (Pso). Research demonstrated STAT3 signalling to be upregulated in Pso. Additionally, Pso results in oxidative stress that activates various signalling pathways like factor nuclear kappa-B (NF-κB). Nitazoxanide (NTZ) is an antiprotozoal drug shown to inhibit the STAT3 pathway. Umbelliferone (UMB) is an antioxidant, and anti-inflammatory and can suppress NF-κB signalling. Therefore, we propose to hypothesize that NTZ and UMB would be effective in treating Pso. Balb/c mice were treated with IMQ to induce Pso. The clinical characteristics of Pso were assessed using the Psoriasis Area and Severity Index (PASI), back skin thickness, spleen length and mass, and histology of the skin sample tissue. In addition, we measured the levels of interleukin-17 (IL-17), tumor necrosis factor-α (TNF-α), STAT3, and NF-κB. Furthermore, to gain the interaction of NTZ and UMB with STAT3, a detailed in-silico study has been performed. The impact of treatment on oxidative stress was evaluated by estimating the activity of superoxide dismutase (SOD) and catalase (CAT). The results demonstrate that mice subjected to IMQ-induced Pso exhibited positive responses to treatment with NTZ and UMB. Additionally, IL-17, TNF-α levels, STAT3, and NF-κB were decreased in NTZ and UMB-treated groups. SOD and CAT levels in NTZ and UMB groups were elevated. Our findings show that NTZ and UMB are potential therapeutic medications for Pso.