Multi-target mechanisms of Bojungikki-tang in psoriasis-like dermatitis: Integrative network and transcriptomic analysis.

BACKGROUND

Psoriasis is a chronic and complex disease characterized by itching, burning, and soreness with scaly plaques and erythematous lesions. It is associated with various comorbidities, such as rheumatoid arthritis, cardiovascular disease, and psychiatric complications. Psoriasis is a systemic inflammatory disease that increases the release of pro-inflammatory cytokines from chronically-activated innate and adaptive immune systems. To treat multifactorial and complex diseases, system-oriented drug design and drug combinations for synergistic effects are highly effective and advantageous. Previous studies have revealed the immunomodulatory effects of Bojungikki-tang (BJT, Buzhong-Yiqi-Tang in traditional Chinese medicine and Hochu-ekki-to in Kampo medicine) in complex diseases; however, the effect of BJT on psoriasis, a chronic autoimmune disease, has not been evaluated.

PURPOSE: We evaluated the effect of BJT against psoriasis and the underlying mechanisms.

METHODS

The anti-psoriatic effects of BJT were evaluated in vivo, and the underlying mechanisms were elucidated through network analysis, transcriptomics, UPLC-ESI-MS/MS, and molecular docking.

RESULTS

In vivo studies confirmed that BJT reduced TNF-α, IL-1β, IL-6, Th17 cytokines, prostaglandin E2 production, and keratinocyte proliferation. Moreover, BJT regulated the expression of PLA2G4D, an enzyme of the arachidonic acid (AA) pathway, as well as other enzymes involved in this pathway, including COX-2.

CONCLUSION

This study demonstrated that BJT ameliorated psoriasis-like inflammation by concurrently regulating pivotal pro-inflammatory cytokines and two distinct steps of the AA pathway, which may be related to its multi-component composition. These findings indicate the therapeutic potential of the multi-component drug BJT on multiple targets for psoriasis-like inflammation.