波尼西丁诱导的HSP90形状变化调节MAPK通路以缓解性结肠炎
Xuerong Zhang1, Yuanhang Xu1, Minqi Fan1
1International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China.
Journal of ethnopharmacology
|November 26, 2023
概括
波尼西丁源自传统中医药,通过向热毒素并促进血液循环,有效地减少性结肠炎 (UC) 模型中的炎症. 这项研究确定了热冲击蛋白90 (HSP90) 作为ponicidin的一个关键分子标.
科学领域:
- 药理学和中国传统医学
- 胃肠道学和免疫学
- 分子生物学和药物发现
背景情况:
- 性结肠炎 (UC) 是一种慢性炎症性肠病,治疗选择有限,需要新的治疗策略.
- 拉布多西亚红,一种传统的中医药,表现出抗炎性质,与ponicidin 确定为一个关键的活性分子.
- 热冲击蛋白90 (HSP90) 是UC等炎症性疾病的关键调节剂,使其成为潜在的治疗标.
研究的目的:
- 在性结肠炎 (UC) 模型中研究ponicidin的抗炎作用和机制.
- 确定ponicidin的特定蛋白质标,并阐明其作用模式.
- 探索ponicidin的潜力作为一种新的治疗药物UC.
主要方法:
- 在C57BL/6小鼠中,使用硫酸 (DSS) 诱导了性结肠炎,并用5和10毫克/公斤的ponicidin.
- 用脂聚糖 (LPS) 刺激RAW264.7巨细胞,以创建一个体外炎症模型,用ponicidin (1-4μM) 治疗.
- 在体外测试,质谱,异热定位热量计,蛋白酶降解和分子动力学模拟中涉及的目标识别.
主要成果:
- 波尼西丁在小鼠的DSS诱导性结肠炎和巨细胞的LPS诱导性炎症中都表现出显著的抗炎活性.
- 该机制涉及在细胞和动物水平上抑制MAPK信号通路.
- 发现ponicidin与HSP90的中间域相互作用,导致其N端域的构造变化.
结论:
- 波尼西丁具有强大的抗炎作用,与性结肠炎治疗有关.
- 这项研究成功地确定了HSP90作为ponicidin的分子标.
- 这些发现揭示了ponicidin与HSP90相互作用的分子机制,为新的UC疗法铺平了道路.
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