Trifolirhizin improves the hyperproliferation and excessive inflammatory response in human HaCaT keratinocytes and ameliorates skin lesions in psoriasis-like mouse models.
Keratinocyte hyperproliferation and excessive inflammatory responses are associated with psoriasis pathogenesis. Trifolirhizin has anti-inflammatory and anti-proliferation effects. The purpose of the study was to investigate the role of trifolirhizin in psoriasis-like skin lesions and its molecular mechanism. Imiquimod-induced psoriasis-like mouse models were treated with trifolirhizin. Skin lesions and inflammatory factors were assessed. In vitro, human HaCaT keratinocytes were stimulated by a mixture of interleukin (IL)-1α, IL-17, IL-22, tumor necrosis factor (TNF)-α, and oncostatin M (M5) to establish a psoriatic keratinocyte model. Cell viability and cycle were assessed via CCK-8 assay and flow cytometry. Inflammatory factors, autophagy levels, and AMPK-mTOR pathway activation were detected by western blot. Trifolirhizin dose-dependently inhibited epidermal layer erythema, scaling, and thickening and reduced epidermal thickness and IL-12 level in an imiquimod-induced psoriasis-like mouse model. Trifolirhizin also inhibited cell viability, PCNA expression, and excessive synthesis and secretion of IL-8 and IL-12 in HaCaT keratinocytes induced by M5. Furthermore, the inhibition of autophagy and AMPK-mTOR pathway could be reversed by trifolirhizin in M5-induced HaCaT keratinocytes and skin lesions from imiquimod-mediated psoriasis-like mouse model. The improvement effects of trifolirhizin could be inhibited by the autophagy inhibitor chloroquine. Trifolirhizin up-regulated autophagy through the AMPK-mTOR pathway, improved the hyperproliferation and excessive inflammatory responses of keratinocytes, thus alleviating psoriatic skin lesions. Trifolirhizin may have therapeutic potential in improving the progression of psoriasis.
