普罗托帕纳克萨迪醇衍生物:一种具有抗炎作用的新型选择性葡萄皮质受体调节剂的植物原产物
Zhenyuan Li1, Teng Liu1, Wenbin Xie1
1School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, Shandong, PR China.
一种植物化合物SP-8像选择性葡萄皮质受体调节器 (SGRM) 一样起作用. 它通过抑制NF-κB通路而减少炎症,而不会引起典型的葡萄糖皮质体副作用,为炎症性疾病治疗提供了潜力.
科学领域:
- 药理学 药理学是指药理学的学科.
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 葡萄糖皮质类药物 (GCs) 具有抗炎性质,但通过交换激活会引起副作用.
- 选择性葡萄糖皮质体受体调节剂 (SGRMs) 的目的是将抗炎作用 (转抑制) 与副作用 (转激活) 分开.
- 研究植物衍生化合物的SGRM类活性对于开发更安全的抗炎疗法至关重要.
研究的目的:
- 为了研究一种植物性化合物SP-8.的选择性葡萄糖皮质体受体调节器 (SGRM) 类属性.
- 阐明SP-8.的GR介导抗炎作用的机制.
- 评估SP-8在炎症性疾病中的治疗潜力.
主要方法:
- 在分子对接和细胞热转移试验 (CETSA) 中,评估SP-8与葡萄糖皮质体受体 (GR) 的结合.
- 使用HepG2和RAW264.7细胞进行体外测试,以评估GR激活,核转位,NF-κB抑制和基因/蛋白质表达.
- 使用DSS诱导的性结肠炎的小鼠模型进行体内研究,以确认抗炎疗效.
主要成果:
- SP-8稳定地与GR活性部位结合,激活GR,诱导核转位,并抑制NF-κB激活.
- SP-8不诱导PEPCK/TAT表达或HepG2细胞中的脂肪沉积,对骨代谢的影响最小.
- SP-8提高GR蛋白表达的调节,而不会造成有害的酸化,并且在体外和体外表现出抗炎作用.
结论:
- SP-8表现出选择性葡萄糖皮质体受体调节器 (SGRM) 类属性,将转抑制与交换活化分开.
- SP-8在体外和体外表现出显著的抗炎作用,特别是在大肠炎模型中.
- SP-8具有相当大的潜力,可以作为治疗炎症疾病的治疗剂.
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