Decryption of Active Constituents and Action Mechanism of the Traditional Uighur Prescription (BXXTR) Alleviating IMQ-Induced Psoriasis-Like Skin Inflammation in BALB/c Mice.

Xiaobo Pang,Yingnan Sun,Le Gao,Tao Wang,Hangyu Wang,Jinhui Wang,Ke Zhang,Long Chen,Jian Huang

doi:10.3390/ijms19071822

Abstract

Bai Xuan Xia Ta Re Pian (BXXTR) is a traditional Uighur medicine ancient prescription in China widely used in the treatment of psoriasis, presenting a high curative rate and few side effects. Given that the active constituents and action mechanism still remain unclear, the aim of this study is to explore the potential active constituents and mechanism of antipsoriasis of BXXTR. Psoriasis-like lesions model in BALB/c mice was induced by Imiquimod (IMQ), including five treatment groups: control group, IMQ-treated group, IMQ-ACITRETIN group (Positive control group), IMQ-BXXTR low dose group, IMQ-BXXTR medium dose group and IMQ-BXXTR high dose group. The Psoriasis Area and Severity Index (PASI) score, skin and ear thickness, and histologic section were collected. The differentially expressed genes were determined by using RNAseq technology and the relevant pathways were analyzed by KEGG database. The ELISA kit and western blot assays were used to detect the related protein expression levels. In addition, the chemical constituents of BXXTR were determined by UPLC-TOF-MS analysis and the potential active constituents were predicted by SEA DOCK and Gene Ontology (GO). The data demonstrated that BXXTR significantly alleviated IMQ-induced psoriasis. RNA-seq analysis showed that BXXTR induced the expression levels of 31 genes; the KEGG analysis suggested that BXXTR could significantly change IL-17-related inflammatory pathways. The ELISA kit confirmed that the expression level of IL-17A protein was significantly reduced. 75 compounds of BXXTR were determined by UPLC-TOF-MS analysis, 11 of 75 compounds were identified as potential active compounds by similarity ensemble approach docking (SEA DOCK) and Gene Ontology (GO). BXXTR reduced the severity of skin lesions by inhibiting IL-17-related inflammatory pathways. The results indicated that BXXTR could suppress psoriasis inflammation by multiple-constituents-regulated multiple targets synergistically. Collectively, this study could provide important guidance for the elucidation of the active constituents and action mechanism of BXXTR for the treatment of psoriasis.

Highlights

Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders characterized by neovascularization, hyperproliferative keratinocytes, abnormal keratinocyte differentiation, generally accompanied by marked parakeratosis and extensive inflammatory cell infiltration, including T cells, neutrophils, and dendritic cells (DCs)
Given that the active constituents and action mechanism remain unclear, the aim of this study is to investigate the therapeutic efficacy of Bai Xuan Xia Ta Re Pian (BXXTR) in IMQ-induced psoriasis-like mice models and elucidate the potential active constituents and action mechanism of BXXTR
The research ideas of “multicomponent, multitarget and cotreatment” were used in this experiment to screen specific targets of the compound preparations and related intervention pathways to explore the mechanism of BXXTR in the treatment of psoriasis [20,21,22]

Summary

Introduction

Psoriasis is one of the most common immune-mediated chronic inflammatory skin disorders characterized by neovascularization, hyperproliferative keratinocytes, abnormal keratinocyte differentiation, generally accompanied by marked parakeratosis and extensive inflammatory cell infiltration, including T cells, neutrophils, and dendritic cells (DCs). Previous studies have shown that the formation of neovascularization in psoriatic skin lesions provides nutritional support for epidermal keratinocyte hyperplasia while inflammatory cells enter the diseased tissue through the highly permeable endothelium. The infiltration of inflammatory cells accelerates the formation of neovascularization. Elevated levels of IL-23 and Th17-associated cytokines in the serum and in cutaneous lesions of psoriatic patients indicate an important role of the IL-23/IL-17 Axis in the pathogenesis of psoriasis, Including IL-23, IL-17, IL-18, IL-22, IL-1β, IL-6 and TNF-α [5]. Therapeutic approaches directed at blocking some of these inflammatory mediators have proven effective in reducing patients’ symptoms

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