Yinxieling Inhibits Keratin 17 to Enhance Mitochondrial Function and Ameliorates Psoriasis-like Lesions

Background: Psoriasis is a chronic skin disease characterized by erythema, scaling, and thickening. Yinxieling is a representative prescription for treating psoriasis developed by Professor Guowei Xuan, a master of traditional Chinese medicine. Keratin 17 is a key biomarker for the diagnosis and treatment of psoriasis, and its overexpression has been shown to impair mitochondrial function. Objectives: This study investigates the mechanism of action of Yinxieling in the treatment of psoriasis. Methods: In vivo, BALB/c mice were induced by imiquimod to create psoriasis-like mice model. Different doses of Yinxieling were administered to the psoriasis-like mice and PASI scores, thickness of epidermis and Keratin 17 expression of psoriasis-like mice were measured. In vitro, Ha- CaT cells were induced by IL-17A, IL-22 and TNF-alpha to establish psoriasis-like cells model. Yinxieling with different concentrations was administered to the psoriasis-like cells and Keratin 17 expression, adenosine triphosphate levels, and oxygen consumption rates were measured. Furthermore, the psoriasis-like cells were transfected with keratin 17 plasmids. Yinxieling intervened in these psoriasis-like cells with continuous high expression of keratin 17 and adenosine triphosphate levels and oxygen consumption rates were measured. Results: Yinxieling significantly improved PASI scores and decreased their epidermal thickness in psoriasis-like mice; Yinxieling also inhibited Krt17 expression in psoriasis-like mice and cells. Yinxieling improved ATP levels and oxygen consumption rate in psoriasis-like cells, and this effect of Yinxieling was abolished when the psoriasis-like cells were transfected with keratin 17 plasmids. Discussion: These findings suggest that Yinxieling alleviates psoriatic inflammation and improves mitochondrial function by downregulating KRT17. The study provides new mechanistic insights into the traditional use of Yinxieling and underscores the link between keratin dysregulation and mitochondrial impairment in psoriatic pathology. Conclusion: Yinxieling inhibits keratin 17 to enhance mitochondrial function and ameliorates psoriasis- like lesions.