Qinzhuliangxue mixture alleviates psoriasis-like skin lesions via inhibiting the IL6/STAT3 axis

J Ethnopharmacol. 2021 Jun 28:274:114041. doi: 10.1016/j.jep.2021.114041. Epub 2021 Mar 20.

Abstract

Ethnopharmacological relevance: Psoriasis is a chronic inflammatory skin disease mediated by immunity. Our pre-clinical studies have proved that QZLX mixture can improve patients' clinical symptoms with psoriasis without noticeable adverse reactions. In a psoriasis-like mouse model induced by imiquimod, QZLX mixture has been shown to alleviate epidermal inflammation and inhibit the hyperproliferation of keratinocytes. However, its related molecular mechanism remains to be elucidated.

Aim of the study: To assess the mechanism of QZLX mixture against psoriasis.

Materials and methods: This study combines network pharmacology and experiments to study the mechanism of QZLX against psoriasis. First, construct the active compound-target network and PPI network. Secondly, determine possible drug targets through Molecular docking and KEGG. Thirdly, high-performance liquid chromatography (HPLC) was used for the quality control of QZLX. Finally, use a mouse model of psoriasis to further confirm the role of QZLX.

Results: (1) Network pharmacology analysis shows that QZLX alleviates psoriasis's epidermal inflammation, and neovascularization may be achieved by inhibiting the IL6/STAT3 signaling pathway. (2) QZLX improves the pathological characteristics of IMQ-induced skin damage in psoriasis-like mice. (3) QZLX inhibits the IL6/STAT3 signaling pathway and reduces the expression of IL-17, IL-23, and TNF-α related to inflammation in peripheral blood, as well as the expression of S100A7 in the lesion area. QZLX is better than MTX in inhibiting neovascularization by down-regulating the expression of HIF-1 and CD31 in the lesion area. Finally, inhibition of Ki67 alleviates the excessive proliferation of keratinocytes.

Conclusion: In sum, this study clarifies the mechanism of QZLX against psoriasis and provides evidence to support its clinical use.

Keywords: Chinese medicine; Experimental verification; Molecular docking technology; Network pharmacology; Psoriasis; Qinzhuliangxue mixture.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Cell Proliferation / drug effects
  • Cytokines / genetics
  • Cytokines / immunology
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / pharmacology
  • Drugs, Chinese Herbal / therapeutic use*
  • Hypoxia-Inducible Factor 1, alpha Subunit / immunology
  • Imiquimod
  • Keratinocytes / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Docking Simulation
  • Phytochemicals / analysis
  • Phytochemicals / pharmacology
  • Phytochemicals / therapeutic use
  • Protein Interaction Maps
  • Psoriasis / chemically induced
  • Psoriasis / drug therapy*
  • Psoriasis / immunology
  • Psoriasis / pathology
  • STAT3 Transcription Factor / immunology
  • Skin / drug effects
  • Skin / immunology
  • Skin / pathology

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Drugs, Chinese Herbal
  • Hif1a protein, mouse
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Phytochemicals
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • qinzhu liangxue
  • Imiquimod