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

Int J Mol Sci. 2018 Jun 21;19(7):1822. 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.

Keywords: BXXTR; active constituent; an-inflammation; mechanism; psoriasis.

MeSH terms

  • Aminoquinolines
  • Animals
  • Cell Proliferation
  • Dermatologic Agents / chemistry
  • Dermatologic Agents / pharmacology*
  • Disease Models, Animal
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology*
  • Gene Expression Regulation
  • Humans
  • Imiquimod
  • Interleukin-17 / genetics
  • Interleukin-17 / immunology
  • Interleukin-18 / genetics
  • Interleukin-18 / immunology
  • Interleukin-23 / genetics
  • Interleukin-23 / immunology
  • Keratinocytes / drug effects*
  • Keratinocytes / immunology
  • Keratinocytes / pathology
  • Male
  • Medicine, Chinese Traditional / methods
  • Mice
  • Mice, Inbred BALB C
  • Psoriasis / chemically induced
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • Psoriasis / pathology
  • Severity of Illness Index
  • Signal Transduction
  • Skin / drug effects*
  • Skin / immunology
  • Skin / pathology
  • Toll-Like Receptor 8 / genetics
  • Toll-Like Receptor 8 / immunology
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Aminoquinolines
  • Dermatologic Agents
  • Drugs, Chinese Herbal
  • Interleukin-17
  • Interleukin-18
  • Interleukin-23
  • TLR8 protein, mouse
  • Toll-Like Receptor 8
  • Transforming Growth Factor beta
  • Tumor Necrosis Factor-alpha
  • Imiquimod