Protective Anti-Inflammatory and Antioxidant Mechanisms of Ohwia caudata Leaf Hydroethanolic Extract in a Dermatitis Mouse Model

Contact dermatitis is a common inflammatory skin disorder characterized by erythematous and pruritic lesions caused by irritant exposure. Ohwia caudata, a traditional medicinal plant, possesses anti-inflammatory and antioxidant properties, but its dermatoprotective potential remains unclear. To investigate the protective effects and mechanisms of Ohwia caudata leaves’ hydroethanolic extract in a murine model of TPA-induced contact dermatitis. Major phytochemicals in Ohwia caudata extract were identified by HPLC–MS. SKH1/J hairless mice were topically treated with Ohwia caudata extract following TPA stimulation. Skin barrier function was assessed by transepidermal water loss and hydration. Inflammatory (IL-6, TNF-α, TGF-β), antioxidant (SIRT1, Nrf2, HO-1), and ERK-related (p-ERK, eIF2α, ATF-4, CHOP) proteins were analyzed by immunoblotting and immunofluorescence. HPLC–MS revealed harmine, swertisin, isoliquiritigenin, eupatilin, 3′,4′-dimethoxyflavone, and nerolidol as key constituents. The extract significantly reduced transepidermal water loss and enhanced hydration, indicating improved barrier integrity. It downregulated IL-6 and TNF-α while restoring TGF-β expression. ERK and downstream eIF2α/ATF-4/CHOP activation were suppressed, whereas SIRT1/Nrf2/HO-1 antioxidant signaling was enhanced. Ohwia caudata leaves hydroethanolic extract protects against TPA-induced dermatitis by improving skin barrier function, suppressing inflammation, and activating antioxidant defense, supporting its potential as a natural therapeutic for inflammatory skin diseases.