The potential effects of ticagrelor and/or sodium butyrate on imiquimod-induced psoriasis in mice model: The role of NLRP3 inflammasome signaling pathway

Background

Psoriasis is a chronic immune-mediated inflammatory skin disease with a huge negative impact on patients’ quality of life and an increasing need to discover new alternatives for psoriasis treatment with better efficacy and fewer adverse effects. This study was designed to investigate the immunomodulatory and anti-inflammatory effects of ticagrelor (TICA) and/or sodium butyrate (NaB) in imiquimod (IMQ)-induced psoriasis model.

Methods

Mice were randomly allocated into five equal groups: control group, untreated IMQ group, IMQ + TICA group, IMQ + NaB group, and IMQ + TICA + NaB group. IMQ cream (62.5 mg) was applied topically on the shaved dorsal skin and 5 mg on the right ear for 7 consecutive days. The treatment protocol started post-induction and for 10 days with daily intraperitoneal injection of (10 mg/kg TICA) and (500 mg/kg NaB). The effects of these drugs on inflammatory, immune-modulatory, pyroptosis, and multi drug resistance 1 (MDR1) levels were assessed.

Results

IMQ + TICA + NaB group showed enhanced amelioration of disease activity, with significant improvements in body weight, Psoriasis area severity index (PASI) score, ear thickness, and spleen index. The levels of the inflammatory and immune markers [interleukin-1β (IL-1β) and IL-17] and MDR1 level, as well as the immunohistochemical expression of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, and nuclear factor-kappa B (NF-κB/p65), were significantly alleviated. Moreover, the superiority of the combination extended to histopathological findings, epidermal thickness, and Baker's scoring.

Conclusion

TICA and NaB might be considered promising candidates for psoriasis treatment via modulation of IL-17 and NF-κB/NLRP3/IL-1β pathway.