Integrating transcriptomics and network pharmacology to reveal the effect and mechanism of Bai-Jie-Jing-Xie ointment on improving skin inflammation of psoriasis

Abstract

Ethnopharmacological relevance

Psoriasis is a global chronic, immune-mediated, inflammatory skin disease. Bai-Jie-Jing-Xie (BJJX) ointment has been widely used in the clinic practice for its notable efficacy and is an empirical prescription for psoriasis treatment in hospitals. Nevertheless, its precise mechanism of action on psoriasis remains unclear.

Aim of the study

To study the mechanism of action of the hospital empirical prescription BJJX in the treatment of psoriasis.

Material and methods

Imiquimod (IMQ) was used to induce the psoriasis model in BALB/c mice and UPLC-MS/MS analysis was used for quality control. Subsequently, a combination of network pharmacology (NP) and Transcriptomic (RNA-Seq) methodology was used to assess the potential targets and mechanisms of action of BJJX on psoriasis. Finally, further validation was performed using flow cytometry, RT-qPCR, and western blotting.

Results

BJJX significantly ameliorated IMQ-induced skin damage in psoriatic mice, reduced keratinocyte proliferation, and inhibited the levels of inflammatory factors (IL-23, IL-22, IL-17A, IL-6, IL-1β, and IL-8). NP predicts that BJJX may exert its therapeutic effects on psoriasis by modulating the IL-17 signaling pathway and Th17 cell differentiation. RNA-Seq analysis showed that BJJX regulated the expression of IL-17 pathway-related genes. Further experimental results demonstrated that BJJX treatment significantly reduced the mRNA expression of inflammatory factors CXCL2, CXCL3, MMP13, IL-1β, IL-23, IL-22, and IL-17A, as well as the proportion of Th17 cells. In addition, BJJX significantly inhibited the protein expression of JAK2 and STAT3.

Conclusions

BJJX attenuated IMQ-induced skin lesions in psoriasis mice by decreasing the expression of cytokines and chemokines mediated by the Th17/IL-17 axis. This study revealed, for the first time, the mechanism used by BJJX to treat psoriasis, providing a new paradigm for its pharmacological role in the clinical treatment of psoriasis.