库尔库莫尔通过向TAK1和抑制MAPK和NF-κB通路来改善西斯普拉丁诱导的毒性
Xuejin Jin1, Miao Yuan1, Lingkun Wang2
1School of Pharmaceutical Sciences, School of Food Science and Engineering, Hangzhou Medical College, Hangzhou, Zhejiang 311399, China.
概括
库尔库莫尔 (CUR) 通过向TAK1并抑制炎症途径,保护免受西斯普拉丁诱导的急性损伤 (AKI). 这种天然化合物显示出作为辅助疗法的承诺,以减轻化疗的作用.
科学领域:
- 药理学和毒理学 药理学和毒理学
- 自然产品化学 自然产品化学
- 脏生理学 脏生理学
背景情况:
- 西斯 (Cis) 是一种重要的化疗剂,但会导致剂量限制性毒性.
- 缺乏有效的治疗西斯普拉丁诱导的急性损伤 (AKI).
- 库尔库摩尔 (CUR) 是来自Curcuma zedoariae的一种基胺,显示器官保护作用,但其在AKI中的作用尚不清楚.
研究的目的:
- 为了研究库尔库莫尔 (CUR) 在西斯 (Cis) 诱导的毒性中产生的保护作用.
- 阐明CUR在AKI中的作用的基础分子机制.
主要方法:
- 在C57BL/6小鼠中,使用西斯 (20 mg/kg) 诱导了AKI.
- 在治疗前和治疗后使用CUR (40/80 mg/kg).
- 在体外研究中使用了人体管状上皮细胞 (HK-2);RNA测序和分子对接确定了机制和目标.
主要成果:
- CUR证明了剂量依赖性脏保护,减少了亡,氧化应激和炎症.
- CUR抑制了酸化介导的MAPK/NF-κB通路激活.
- 分子对接和CETSA表明CUR和TAK1之间的直接相互作用,这对CUR的保护作用至关重要.
结论:
- 库尔库莫尔 (CUR) 通过向TAK1并抑制MAPK和NF-κB通路来改善西斯普拉丁诱导的AKI.
- CUR显示出作为辅助疗法的潜力,以减少西斯的毒性.
- 这些发现强调了CUR作为AKI的有前途的治疗剂.
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