Study on the Mechanism of Wanxuandi Ointment in Treating Imiquimod-induced Psoriasis in Mice by Modulating JAK2/STAT3 Inflammatory Signaling Pathway
Objective To investigate the effect and mechanism of Wanxuandi Ointment (WXD) on imiquimod-induced psoriasis in mice. Methods A psoriasis mice model was established by applying imiquimod to the hairless area on the back of the mice for 7 consecutive days. In the study of the time-effect relationship,mice were randomly separated into normal group,model group,groups of 1st,2nd,3rd,4th day of WXD-medication,and mometasone furoate (MF) group. The corresponding ointment was rubbed into the skin once daily. In the study of dose-effect relationship,mice were randomly separated into normal group,model group,groups of 1,2,3 time of WXD-medication,and MF group. These drugs were rubbed into the skin at the 4th day of modeling. The psoriasis area and severity index (PASI)and pathological observation were used to evaluate the effect of WXD on psoriasis. The mRNA expressions of TNF-α and IL-1β in the skin were detected by qRT-PCR. The content of IL-23,IL-17A,5-HT and histamine were detected by ELISA. The protein expressions of myeloperoxidase (MPO)and p-JAK2 in the skin were detected by immunohistochemistry. The protein expression of p-STAT3 was detected by Western Blot. Results The results of time-effect relationship showed that PASI,thickness of stratum spinosum,length of drumstick-shaped protrusion of stratum spinosum,area of drumstick-shaped protrusion of stratum spinosum/stratum spinosum area were obviously reduced in groups of 1st,2nd,3rd,4th day of WXD-medication (P<0.05,P<0.01). The results of dose-effect relationship suggested that all above mentioned indexes in group of 1 time of WXD-medication were also significantly decreased (P<0.05,P<0.01). Additionally,WXD significantly reduced the protein expression of MPO,p-JAK2,p-STAT3,IL-23 and IL-17A,and the mRNA expressions of TNF-α and IL-1β in skin tissues of psoriasis mice,as well as the serum levels of 5-HT and histamine (P<0.05,P<0.01). Conclusion WXD administration for prevention during the model establishment and therapeutic treatment of WXD in the stage of obvious psoriasis symptoms are effective,once-daily administration of WXD is considered be the best treatment for psoriasis. The possible mechanism is related to inhibiting inflammatory response by down-regulating JAK2/STAT3 signaling pathway.
万方数据
维普
