Zingiber officinale essential oil mitigates psoriasis-like skin inflammation by modulating inflammatory and proliferative responses: in-silico, in-vitro, and in-vivo studies.

Psoriasis, a chronic skin disease characterized as keratinocytes hyperproliferation and inflammation, remains a clinical challenge due to limitations of long-term synthetic drug therapy. Plant drugs can meet this limitation therefore, in this study, we investigated the anti-psoriatic potential of Zingiber officinale (ginger) essential oil (ZOEO) through in-silico, in-vitro, and in-vivo approaches. GC/GC-MS analysis was done to characterize the phytochemical profile of ZOEO and analysis identified α-zingiberene, β-sesquiphellandrene, β-bisabolene, camphene, and ar-curcumene as major phytoconstituents. In-silico molecular docking and dynamics simulations were conducted that showed strong binding affinities of these phytoconstituents toward psoriasis-related targets IL-23, IL-22, TNF-α, and NF-κB. For in-vitro study, qRT-PCR and ELISA were performed to quantify TNF-α, IL-6, IL-1β, IL-17 A, and IL-23 levels; and immunofluorescence analysis was used to evaluate NF-κB translocation in LPS-induced inflammation in RAW 264.7 macrophages. The anti-proliferative effects were assessed via cell scratch assay, proliferation assays, and TNF-α-induced cytokine production such as IL-6, IL-17 A, IL-22, and IL-23 in HaCaT keratinocytes. Results showed that ZOEO significantly suppressed inflammatory mediators and keratinocyte proliferation. For Iin-vivo study, PASI scores, CosCam scores, qRT-PCR, ELISA, histopathology, and immunohistochemical analysis of specific markers (IL-23, IL-17, CCR6, and NF-κB) were performed to evaluate the effectiveness of topically applied ZOEO against IMQ-induced psoriasis-like skin inflammation in BALB/c mice. ZOEO significantly reduced psoriasis-like symptoms, decreased inflammatory cytokine levels (TNF-α, IL-6, IL-1β, IL-17 A, and IL-23), and downregulated the IL-23-IL-17 A signalling axis. Acute dermal toxicity was assessed in CF rats and rabbits as per OECD guidelines and no signs of dermal toxicity were observed in both models. In conclusion, ZOEO exhibits significant anti-psoriatic activity through modulation of inflammatory and proliferative pathways and highlights the potential of ZOEO as a safe phytomedicine for the management of psoriasis.