Topical treatment of Ginkgolide a ameliorates psoriasiform dermatitis by suppressing M1 macrophage polarization by the blockade of PI3K/AKT/c-JUN pathways.

Psoriasis (PsO) is a chronic, relapsing inflammatory skin disease. While targeted biologics have improved outcomes, limitations in long-term remission and safety concerns underscore the urgent need for cost-effective, safe, and potent topical therapies. Here, we investigated the therapeutic potential of Ginkgolide A (GA) for mild-to-moderate PsO. To maximize local efficacy and circumvent first-pass metabolism, we formulated a GA oily solution for topical administration. This administration of GA effectively alleviated IMQ-induced psoriasis-like dermatitis in mice. Furthermore, safety assessments confirmed that this topical approach is well-tolerated with no obvious toxicity under the tested conditions. Mechanistically, GA directly suppressed M1 macrophage polarization, as evidenced by reduced pro-inflammatory cytokine production (TNF-α, IL-6, IL-1β). Time-course signaling analysis revealed that GA concurrently inhibits the PI3K-AKT axis, with mTOR, JNK and ERK being unaffected. In conclusion, our findings position the GA oily solution as a promising, cost-effective, and potent topical candidate for psoriasis, addressing a persistent clinical gap while offering translational implications for other related immune-mediated diseases.