<i>Stachys byzantina</i> K. Koch in the Treatment of Skin Inflammation: A Comprehensive Evaluation of Its Therapeutic Properties

<i>Stachys byzantina</i> is a plant widely cultivated for food and medicinal purposes. <i>Stachys</i> species have been reported as anti-inflammatory, antibacterial, anxiolytic, and antinephritic agents. This study aimed to evaluate the anti-inflammatory potential of the ethanolic extract (EE) from the aerial parts of <i>S. byzantina</i> and its most promising fraction in models of acute and chronic inflammation, including a psoriasis-like mouse model. The EE was fractionated into hexane (HF), dichloromethane (DF), ethyl acetate (AF), and hydroalcoholic (HD) fractions. Screening for anti-inflammatory activity based on nitric oxide inhibition (IC₅₀ μg/mL: HF 24.29 ± 5.87, EE 176.45 ± 18.65), hydroxyl radical scavenging (HF 3.89 ± 0.61, EE 6.38 ± 2.25), β-carotene/linoleic acid assay (HF 10.13 ± 3.81, EE 25.64 ± 2.12), and ORAC identified HF as the most active fraction. Topical application of HF effectively reduced croton oil- and phenol-induced ear edema in mice, with no statistical difference to the reference drugs. A formulation containing HF showed significant activity in the imiquimod-induced psoriasis model, reducing pro-inflammatory cytokines and nitric oxide production in macrophages, with no cytotoxicity to skin cells. Phytochemical analysis of HF revealed the presence of terpenes, steroids (491.68 ± 4.75 mg/g), phenols (34.30 ± 4.96 mg/g), flavonoids (151.77 ± 6.66 mg/g), and α-tocopherol, which was identified and quantified by HPLC-UV analysis (10.56 ± 0.97 mg/g of HF). These findings highlight the therapeutic potential of <i>S. byzantina</i> for skin inflammation, particularly contact dermatitis and psoriasis, encouraging further studies, including in human volunteers.