Alantolactone Suppresses Proliferation and the Inflammatory Response in Human HaCaT Keratinocytes and Ameliorates Imiquimod-Induced Skin Lesions in a Psoriasis-Like Mouse Model

Abstract

Psoriasis is an immune-mediated inflammatory disease that affects 2% to 3% of the world population. Alantolactone, a sesquiterpene lactone, was isolated from Inula helenium and Radix inulae and has several biological effects, including antifungal, anthelmintic, antimicrobial, anti-inflammatory, antitrypanosomal, and anticancer properties. This study aimed to evaluate the antipsoriatic potential of alantolactone in vitro and in vivo and to explore its underlying mechanisms. These results showed that alantolactone significantly attenuated IL-17A, IL-22, oncostatin M, IL-1α, and TNF-α (M5) cytokine-induced hyperproliferation in HaCaT keratinocytes. Moreover, M5 cytokines significantly upregulated the mRNA levels of TNF-α, IL-6, IL-1β, and IL-8. However, alantolactone attenuated the upregulation of these inflammatory cytokines. In addition, alantolactone was found to inhibit STAT3 phosphorylation and NF-κB p65 nuclear translocation in HaCaT keratinocytes. Furthermore, alantolactone treatment in mice significantly alleviated the severity of skin lesions (erythema, scaling and epidermal thickness, and inflammatory cell infiltration) and decreased the mRNA expression of inflammatory cytokines (e.g., TNF-α, IL-6, IL-1β, IL-8, IL-17A, and IL-23) in an IMQ-induced-like mouse model. Therefore, our new findings revealed that alantolactone alleviates psoriatic skin lesions by inhibiting inflammation, making it an attractive candidate for future development as an antipsoriatic agent.

Keywords

• alantolactone
• cytokine
• keratinocytes
• STAT3
• NF-κB p65
• psoriasis