Potential mechanism of oral baicalin treating psoriasis via suppressing Wnt signaling pathway and inhibiting Th17/IL-17 axis by activating PPARγ
Potential mechanism of oral baicalin treating psoriasis via suppressing Wnt signaling pathway and inhibiting Th17/IL-17 axis by activating PPARγ
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DOI：
10.1002/ptr.7546
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发表时间：
2022-07-02
影响因子：
7.2
通讯作者：
Li, Xinyu
中科院分区：
文献类型：
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作者：
Chen, Yi;Song, Shasha;Li, Xinyu
银屑病(PSO)是一种免疫介导的慢性炎症性皮肤病，严重影响患者的生活质量。寻找成本更低、副作用更少的有效药物是当务之急。黄芩苷(HQG)是黄芩中的主要生物活性物质，具有抗炎和免疫调节作用。在此，我们探讨了口服黄精颗粒对PSO的治疗作用及其可能的机制。首先，运用网络药理学方法预测黄精颗粒可能作用于雌激素、肿瘤坏死因子-α(TNF-α)、白介素17(IL-17)信号通路和Th17细胞分化，尤其是关键靶点包括肿瘤坏死因子、原癌基因酪氨酸蛋白激酶Src、过氧化物酶体增殖物激活受体-γ和基质金属蛋白酶-9。采用咪喹莫特(imiquimod，ImQ)诱导的小鼠模型，观察黄芪颗粒对PSO的治疗作用。HQG能明显改善ImQ诱导的小鼠皮肤损伤，降低炎症因子水平，抑制Th1/Th17细胞分化。最后，皮肤损伤的转录组分析结合网络药理学的预测进一步表明，其潜在的机制可能与抑制Wnt信号通路和通过激活PPAR-γ而抑制Th17/IL-17轴有关。综上所述，本研究提示HQG可能是一种有前途的药物，可用于未来寻找治疗PSO的治疗策略。
Psoriasis (PSO), an immune-mediated chronic inflammatory skin disease, has seriously affected the quality of patients' life. It is urgent to find effective medicines with lower costs and less side effects. Baicalin (HQG) is the main bioactive substance from Scutellaria baicalensis with effects of anti-inflammation and immunoregulation. Herein, we explored the effect of oral HQG treating PSO and its potential mechanism. Firstly, network pharmacology was used to predict that HQG may act on Estrogen, TNF-alpha (tumor necrosis factor, TNF), interleukin-17 (IL-17) signaling pathways and Th17 cell differentiation, especially the key targets including TNF, Proto-oncogene tyrosine-protein kinase Src, Peroxisome proliferator-activated receptor gamma and Matrix metalloproteinase-9. Imiquimod (IMQ)-induced mice were then used to study the effects of HQG treating PSO. HQG could significantly ameliorate the skin lesions, decrease the level of inflammatory factors and inhibit Th1/Th17 cell differentiation in IMQ-induced mice. Finally, transcriptome analysis of skin lesions integrated with the prediction of network pharmacology further demonstrated that the potential mechanism may be associated with suppressing Wnt signaling pathway and inhibiting Th17/IL-17 axis by activating PPAR gamma. In conclusion, this study suggested that HQG may be a promising agent for further studies in the search for therapeutic strategies to treat PSO in the future.