Wang Dongna, Tang Wenyan, Sun Neng, Cao Kaimei, Li Qinghuan, Li Shuai, Zhang Chenggui, Zhu Jianquan, Zhu Jiali
College of Pharmacy, Dali University, Dali, 671000, China.
Yunnan Provincial Key Laboratory of Entomological Biopharmaceutical R&D, Dali University, Dali, 671000, China.
Inflammation. 2024 Nov 22. doi: 10.1007/s10753-024-02188-y.
Psoriasis is a common chronic inflammatory skin disease, that always seriously decreases the patient's quality of life. To date, the drugs used to treat psoriasis have severe side effects and poor efficacy, making the development of new drugs urgent. Scopoletin (SCP), a coumarin component extracted from plants such as Artemisia indica and Arabidopsis thaliana, was reported to have anti-inflammatory and immunomodulatory effects. In this study, network pharmacology and molecular docking techniques were utilized to predict the potential possibilities and mechanism of SCP's therapeutic effects on psoriasis. It was shown that SCP may mainly affect interleukin-17 (IL-17), tumor necrosis factor (TNF) and phosphoinositide-3 kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway, especially the key targets including TNF, Akt1, IL-6, epidermal growth factor receptor (EGFR) and heat shock protein 90 alpha family class A member 1 (HSP90AA1). Imiquimod (IMQ)-induced psoriasis-like mice were used to verify the therapeutic effects of SCP. We observed SCP could significantly alleviate psoriasis-like skin symptoms, improve the pathological changes, inhibit spleen enlargement and decrease the expression of inflammation factors in IMQ-induced mice. Besides, SCP could also inhibit the phosphorylation of PI3K, Akt, and mTOR, and the good docking activity of SCP with the three pathway proteins further proved SCP can treat psoriasis via PI3K/Akt/mTOR signaling pathway. In conclusion, SCP may be a potential drug for treating psoriasis and is worth further research.
银屑病是一种常见的慢性炎症性皮肤病，严重降低患者的生活质量。迄今为止，用于治疗银屑病的药物副作用严重且疗效不佳，因此开发新药迫在眉睫。东莨菪素（SCP）是从印度蒿和拟南芥等植物中提取的一种香豆素成分，据报道具有抗炎和免疫调节作用。在本研究中，利用网络药理学和分子对接技术预测SCP对银屑病治疗作用的潜在可能性和机制。结果表明，SCP可能主要影响白细胞介素-17（IL-17）、肿瘤坏死因子（TNF）和磷脂酰肌醇-3激酶/蛋白激酶B/雷帕霉素哺乳动物靶蛋白（PI3K/Akt/mTOR）信号通路，尤其是包括TNF、Akt1、IL-6、表皮生长因子受体（EGFR）和热休克蛋白90α家族A类成员1（HSP90AA1）在内的关键靶点。采用咪喹莫特（IMQ）诱导的银屑病样小鼠来验证SCP的治疗效果。我们观察到SCP可显著减轻银屑病样皮肤症状，改善病理变化，抑制脾脏肿大，并降低IMQ诱导小鼠中炎症因子的表达。此外，SCP还可抑制PI3K、Akt和mTOR的磷酸化，SCP与三种通路蛋白的良好对接活性进一步证明SCP可通过PI3K/Akt/mTOR信号通路治疗银屑病。总之，SCP可能是一种治疗银屑病的潜在药物，值得进一步研究。
