Total glucosides of paeony attenuates animal psoriasis induced inflammatory response through inhibiting STAT1 and STAT3 phosphorylation
Total glucosides of paeony attenuates animal psoriasis induced inflammatory response through inhibiting STAT1 and STAT3 phosphorylation
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DOI：
10.1016/j.jep.2019.112121
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发表时间：
2019-10-28
影响因子：
5.4
通讯作者：
Fang, Weirong
中科院分区：
文献类型：
--
作者：
Li, Binbin;He, Shucheng;Fang, Weirong
民族药理学相关性：银屑病是一种免疫系统介导的疾病，尤其是T细胞。它困扰着世界各地的许多人，难以治疗。芍药在中国已有数千年的药用历史。近年来研究发现，芍药的主要成分能增强多种疾病的免疫反应。本研究以白芍总苷（total glucosides of paeony，TGP）为研究对象，采用5%普萘洛尔乳膏（propranolol cream）和咪喹莫特（Imiquimod，IMQ）乳膏（cream）诱导的豚鼠银屑病模型和小鼠银屑病模型，观察TGP对银屑病的治疗作用，并探讨其可能的作用机制。取耳厚度，H&E染色观察病理损伤。血清IL-1 β、IL-6、IL-12、IL-17、IL-23、TNF-α和IFN-γ、皮肤IL-17 A、IL-22和孤儿核受体的水平（ROR γ t）mRNA表达、增殖细胞核抗原（PCNA）、总或磷酸化信号转导和转录激活因子分别采用酶联免疫吸附试验（ELISA）、真实的时间PCR、免疫组化染色和蛋白质印迹法检测STAT 1、STAT 3的表达。与模型组相比，白芍总苷治疗组可减轻银屑病大鼠耳廓厚度，改善银屑病病理，减轻IMQ诱导的角质形成细胞增殖，降低炎症细胞因子，下调IL-17 A、IL-22，和ROR γ t mRNA。结论：白芍总苷对银屑病样豚鼠和小鼠皮损中STAT 1和STAT 3的磷酸化有明显的抑制作用，其作用机制可能与抑制STAT 1和STAT 3磷酸化从而抑制T辅助细胞17（TH 17）分化和角质形成细胞增殖有关。
Ethnopharmacological relevance: Psoriasis is an immune system meditated disease, especially T cells. It disturbed many people around the world and hard to therapy. Paeonia lactiflora Pall has been used as a medicine in china for thousands of years. Recent studies found that the main component of Paeonia lactiflora Pall can alleviates the immune response in many diseases. In this study, we researched the effects and possible mechanisms of total glucosides of paeony (TGP) on animal psoriasis.Aim of the study: To study the therapeutic effects and mechanisms of TGP in 5% propranolol cream-induced psoriasis in guinea pigs and Imiquimod (IMQ) cream-induced psoriasis in mice.Materials and methods: The effect of TGP was evaluated using a psoriasis-like model of guinea pigs and mice. Ear thickness was accessed, and pathology injury was observed by H&E staining. The levels of serum IL-1 beta, IL-6, IL-12, IL-17, IL-23, TNF-alpha, and IFN-gamma, skin IL-17A, IL-22 and orphan nuclear receptor (ROR gamma t) mRNA expression, proliferating cell nuclear antigen (PCNA), total or phosphorylated signal transducers and activators of transcription (STAT1, STAT3) were determined by enzyme linked immunosorbent assays (ELISAs), real time PCR, immunohistochemical staining, and western blotting, respectively.Results: Compared with model group, TGP treatment decreased the ear thickness, improved pathology of psoriasis, alleviated IMQ-induced keratinocyte proliferation, reduced the inflammatory cytokine, and downregulated IL-17A, IL-22, and ROR gamma t mRNA in mice. Further study indicated that TGP inhibited STAT1 and STAT3 phosphorylation in lesion skins of psoriasis-like mice.Conclusions: TGP alleviates the symptoms of psoriasis-like guinea pigs and mice, and the possible mechanism may relate to inhibit T helper 17 (TH17) cell differentiation and keratinocytes proliferation by inhibiting STAT1 and STAT3 phosphorylation.