PAMs ameliorates the imiquimod-induced psoriasis-like skin disease in mice by inhibition of translocation of NF-κB and production of inflammatory cytokines.

Rongkun Dou,Diqiang Li,Xue Yuan,Wei Su,Piao Yang,Zongying Liu,Danzhou Xiangfei,Zhenfei Bi,Yalan Yang,Yinsong Dong,Ruixue Bai,Canquan Mao,Andrzej T Slominski

doi:10.1371/journal.pone.0176823

Abstract

Psoriasis is a chronic and persistent inflammatory skin disease seriously affecting the quality of human life. In this study, we reported an ancient formula of Chinese folk medicine, the natural plant antimicrobial solution (PAMs) for its anti-inflammatory effects and proposed the primary mechanisms on inhibiting the inflammatory response in TNF-α/IFN-γ-induced HaCaT cells and imiquimod-induced psoriasis-like skin disease mouse model. Two main functional components of hydroxysafflor Yellow A and allantoin in PAMs were quantified by HPLC to be 94.2±2.2 and 262.9±12.5 μg/mL respectively. PAMs could significantly reduce the gene expression and inflammatory cytokines production of Macrophage-Derived Chemokine (MDC), IL-8 and IL-6 in TNF-α/IFN-γ-induced HaCaT cells. PAMs also significantly ameliorates the psoriatic-like symptoms in a mouse model with the evaluation scores for both the single (scales, thickness, erythema) and cumulative features were in the order of blank control < Dexamethasone < PAMs < 50% ethanol < model groups. The results were further confirmed by hematoxylin-eosin staining, RT-qPCR and immunohistochemistry. The down-regulated gene expression of IL-8, TNF-α, ICAM-1 and IL-23 in mouse tissues was consistent with the results from those of the HaCaT cells. The inhibition of psoriasis-like skin inflammation by PAMs was correlated with the inactivation of the translocation of P65 protein into cellular nucleus, indicating the inhibition of the inflammatory NF-κB signaling pathway. Taken together, these findings suggest that PAMs may be a promising drug candidate for the treatment of inflammatory skin disorders, such as psoriasis.

Highlights

Skin is the largest body’s organ serving as the barrier between the environment and internal milieu, and involved in numerous biological processes, such as skin immune, pigmentary, epidermal and adnexal systems [1]
HPLC chromatograms were obtained using an isocratic flow under different conditions for the two main active components of hydroxysafflor Yellow A and allantoin in plant antimicrobial solution (PAMs)
Nuclear factor-κB (NF-κB) is thought to play a key role in inflammatory signaling pathways by regulation of many cytokines [9,37]. We found that it could regulate the production of TNF-α, IL-8, IL-23 and ICAM-1 associated with psoriasis

Summary

Introduction

Skin is the largest body’s organ serving as the barrier between the environment and internal milieu, and involved in numerous biological processes, such as skin immune, pigmentary, epidermal and adnexal systems [1]. PAMs ameliorates skin disease salary for Ms Danzhou Xiangfei (who is a Co-PI of the funded project), Mr Yinsong Dong and Wei Su, whose main roles are the preparation and the quality control of PAMs. The company did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of these three authors is articulated in the ‘author contributions’ section

Methods

Results

Discussion

Conclusion