揭示 Scopoletin 通过抑制 PI3K/Akt/mTOR 信号通路改善牛皮癣样皮肤症状的机制

IF 4.5 2区 医学 Q2 CELL BIOLOGY Inflammation Pub Date : 2024-11-22 DOI:10.1007/s10753-024-02188-y
Dongna Wang, Wenyan Tang, Neng Sun, Kaimei Cao, Qinghuan Li, Shuai Li, Chenggui Zhang, Jianquan Zhu, Jiali Zhu
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引用次数: 0

摘要

银屑病是一种常见的慢性炎症性皮肤病,总是严重降低患者的生活质量。迄今为止,治疗银屑病的药物副作用大、疗效差,因此开发新药迫在眉睫。据报道,从茵陈蒿和拟南芥等植物中提取的香豆素成分莨菪亭(SCP)具有抗炎和免疫调节作用。本研究利用网络药理学和分子对接技术预测了 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/哺乳动物雷帕霉素靶标(PI3K/Akt/mTOR)信号通路,尤其是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)等关键靶点。我们利用咪喹莫特(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能明显减轻IMQ诱导的银屑病样小鼠的皮肤症状,改善病理变化,抑制脾脏肿大,降低炎症因子的表达。此外,SCP还能抑制PI3K、Akt和mTOR的磷酸化,SCP与这三种通路蛋白良好的对接活性进一步证明了SCP能通过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。
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Uncovering the Mechanism of Scopoletin in Ameliorating Psoriasis-Like Skin Symptoms via Inhibition of PI3K/Akt/mTOR Signaling Pathway.

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.

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来源期刊
Inflammation
Inflammation 医学-免疫学
CiteScore
9.70
自引率
0.00%
发文量
168
审稿时长
3.0 months
期刊介绍: Inflammation publishes the latest international advances in experimental and clinical research on the physiology, biochemistry, cell biology, and pharmacology of inflammation. Contributions include full-length scientific reports, short definitive articles, and papers from meetings and symposia proceedings. The journal''s coverage includes acute and chronic inflammation; mediators of inflammation; mechanisms of tissue injury and cytotoxicity; pharmacology of inflammation; and clinical studies of inflammation and its modification.
期刊最新文献
Inhibiting NLRP3 Inflammasome Activation to Alleviate Retinal Inflammation and Protect the Optic Nerve of OPTN(E50K)Mice. Uncovering the Mechanism of Scopoletin in Ameliorating Psoriasis-Like Skin Symptoms via Inhibition of PI3K/Akt/mTOR Signaling Pathway. Silencing of SH3BP2 Inhibits Microglia Activation Via the JAK/STAT Signaling in Spinal Cord Injury Models. STC-1 alleviates airway inflammation by regulating epithelial cell apoptosis through the 5-LO pathway. Fibroblast growth factor 10 alleviates LPS-induced acute lung injury by promoting recruited macrophage M2 polarization.
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