Qingre Lishi Decoction ameliorates imiquimod-induced psoriasis-like skin lesions in SKH-1 mice by regulating the Treg-DC-Th17 axis and inhibiting MAPK-mediated DC maturation

J Ethnopharmacol. 2024 Jan 10;318(Pt A):116931. doi: 10.1016/j.jep.2023.116931. Epub 2023 Jul 18.

Abstract

Ethnopharmacological relevance: Psoriasis, an immune system disorder, is a chronic relapsing disease that cannot be cured. Chinese herbal medicine is gradually considered a promising alternative treatment for psoriasis due to its multiple effects, ability to target multiple pathways and lower toxicity. Qingre Lishi Decoction (QRLSD) is effective in clinical treatment. However, its related molecular mechanism remains to be elucidated.

Aim of the study: The purpose of this research was to investigate the therapeutic impacts of Qingre Lishi Decoction on the murine model of psoriasis-like skin lesions induced by imiquimod and to reveal the underlying mechanisms.

Materials and methods: First, QRLSD was orally administered to evaluate its efficacy in an imiquimod (IMQ)-induced psoriasis mouse model. Further, UPLC-Q-TOF/MS was used to analyze the compounds of QRLSD. To investigate the mechanism and main targets of QRLSD for treating psoriasis, network pharmacology and molecular docking methods were utilized. Finally, To further confirm the anti-psoriasis target, dendritic cells derived from bone marrow (BMDCs) were cultured in vitro.

Results: In vivo experiments found that QRLSD could regulate the ratio of dendritic cells, Treg cells, and Th17 cells in the body and inhibit inflammation and keratinocyte proliferation in psoriasis-like skin lesions. Further analysis showed that the p38-MAPK pathway is one of its main signaling pathways. In vitro experiments confirmed that QRLSD suppressed the maturation and activation of BMDCs via the p38-MAPK signaling pathway.

Conclusions: This study suggests that Qingre Lishi Decoction has the promise to be an effective formula for treating psoriasis through the p38-MAPK pathway, which can help break through the current limitations of psoriasis in clinical treatment.

Keywords: Dendritic cell; Network pharmacology; Psoriasis; Qingre Lishi Decoction; Regulatory T cell; p38MAPK.

MeSH terms

  • Aminoquinolines / adverse effects
  • Animals
  • Disease Models, Animal
  • Imiquimod
  • Mice
  • Mice, Inbred BALB C
  • Molecular Docking Simulation
  • Psoriasis* / chemically induced
  • Psoriasis* / drug therapy
  • Skin
  • Skin Diseases* / metabolism
  • T-Lymphocytes, Regulatory / metabolism
  • Th17 Cells

Substances

  • Imiquimod
  • Aminoquinolines