Effects of luteolin on treatment of psoriasis by repressing HSP90

Abstract

Aims: This study was conducted to further clarify the efficacy and potential of luteolin in treating psoriasis and to explore its inner mechanisms.

Methods: A pharmacology network displayed the construction of a drug disease target prediction method. The prediction technique was validated via cell experiments in vitro and animal experiments in vivo, respectively. The effects of IFN-γ and luteolin were detected in HaCaT cells. The secretion of exosome and expression of mRNA and protein were detected to explain the relationship between luteolin's regulation of HSP90 (HSP90α and HSP90β) activity in vitro. An in vivo psoriasis mouse model was established to further explore the efficacy of luteolin. Morphological and histological changes in skin lesions were observed, and the CD63, calnexin, Hsp90α, and Hsp90β protein expression was analyzed. Peripheral blood mononuclear cells (PBMCs) were separated and detected via flow pattern analysis to determine how luteolin effects the immune cells in a psoriasis model.

Results: Luteolin as a candidate compound is predicted to have a molecular-target correspondence with HSP90 according to a pharmacology network analysis. Cell experiments indicated that the pathogenesis of psoriasis was significantly related to the increase in IFN-γ, which promoted the transcriptional expression and exosome secretion of HSP90 in HaCaT cells; conversely, luteolin inhibited those and alleviated the promotion of IFN-γ. The effect of luteolin on HSP90 was slightly weaker than that of INF-γ. Animal experiments indicated that the efficacy of luteolin was similar to that of 17-AAG, which both alleviated skin tissue lesions and symptoms, improved the expression of Hsp90 mRNA and protein in skin tissue, and promoted exosome secretion of Hsp90 in plasma. For immune cells in mice with psoriasis, luteolin reduced the proportion of Th1/Th2 and Th17/Treg and inhibited the increase in Th1 and Th17 in the peripheral blood.

Conclusion: Luteolin can relieve the lesions and symptoms of psoriasis through reversing the effects of IFN-γ, inhibiting the expression and exosome secretion of HSP90, and regulating the proportion of immunocytes. Therefore, this study provides the possible mechanisms and potential utilization of luteolin as a novel treatment for psoriasis.

Keywords: Exosome; HSP90; Luteolin; Psoriasis.