Enhanced Anti-inflammatory Effects of 18β-Glycyrrhetinic Acid and Hesperetin for the Treatment of Psoriasis: Evidence from LPS-stimulated RAW264.7 Cells and Imiquimod-induced Psoriasis Mouse Model.

Psoriasis is a persistent, immune-driven inflammatory skin disorder impacting an estimated 125 million individuals globally. The pursuit of effective and safe treatments at affordable costs remains an ongoing challenge. Phytochemicals show promise due to their anti-inflammatory and immunomodulatory effects. Phytochemicals 18β-glycyrrhetinic acid (GA) and hesperetin (HST) exhibit excellent anti-inflammatory properties in cells; however, their low oral bioavailability in the blood compromises their therapeutic potential. This study aimed to evaluate the combined effects of GA and HST in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and an imiquimod (IMQ)-induced psoriasis mouse model. The results demonstrated that GA and HST synergistically inhibited nitric oxide production at a 1:1 concentration ratio in vitro. The combination also reduced IL-1β and IL-6 levels in LPS-stimulated RAW264.7 cells more effectively than either compound alone. Compared with either treatment alone, the combination of these two compounds significantly reduced the PASI scores, spleen index, Baker's histology score, and pro-inflammatory cytokines IL-1β, IL-6, IL-17, IL-22, IL-23, and TNF-α in the IMQ-induced psoriasis mouse model. Moreover, this combination also significantly upregulated the expression of the anti-inflammatory cytokine IL-10. The anti-psoriatic effects of this combination are comparable to the reference drug methotrexate. This research provides a rationale for the combination of GA and HST as an effective anti-psoriatic agent.