Hesperidin inhibits keratinocyte proliferation and imiquimod-induced psoriasis-like dermatitis via the IRS-1/ERK1/2 pathway.


Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China; Beijing Key Laboratory of Clinic and Basic Research with Traditional Chinese Medicine on Psoriasis, Beijing 100010, China; Beijing University of Chinese Medicine, Beijing 100029, China. Electronic address: [Email]


OBJECTIVE : To evaluate the therapeutic benefits of Hesperidin (Hes) using an imiquimod (IMQ)-induced psoriasis-like mouse model and human immortalized keratinocytes (HaCaT) cells stimulated with lipopolysaccharide (LPS).
METHODS : Mice were treated with IMQ and orally administered Hes (125-500 mg/kg/day), methotrexate (MTX) 1 mg/kg/day or distilled water. HaCaT cells were stimulated with LPS (1 μg/mL) and relevant indices were measured after administration with different concentrations of Hes (5-20 μg/mL) for 24 h. Inflammatory skin lesions in IMQ mice were evaluated using the psoriasis area severity index (PASI) and pathological staining. Proteins in the IRS-1/ERK1/2 pathway and inflammatory factors were assessed using western blotting or quantitative real-time PCR. In addition, factors related to IRS-1 secretion levels were assessed by enzyme-linked immunosorbent assays. Extracellular flux (XF) analysis was used to assess cellular metabolic levels.
RESULTS : Hes significantly improved psoriasis-like skin lesions of IMQ-treated mice and inhibited LPS-induced HaCaT cell proliferation. In addition, Hes remarkably decreased PASI scores, reduced epidermal thickness, decreased proliferation and differentiation of epidermal cells, inhibited mRNA expression of inflammatory factors, reduced local skin lesions and serum insulin and glucose levels. Furthermore, Hes modulated the secretion levels of serum Leptin, Adiponectin and Resistin, and inhibited the activation of the IRS-1/ERK1/2 signaling pathway and regulated HaCaT cells metabolism.
CONCLUSIONS : This study demonstrated that Hes administration could have significant therapeutic value for the prevention and clinical treatment of psoriasis.



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