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斯特里赫尼精液和两个类成分通过TRADD-MAPK/NF-κB通路导致HK-2细胞的亡

Wenyi Tian¹, Yuling Li², Fengzhi Liu¹

¹College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.

Toxicon : official journal of the International Society on Toxinology

|January 11, 2025

概括

斯特里奇尼精液及其类化合物通过激活MAPK和NF-κB通路引起细胞 (HK-2) 毒性和亡. 抑制TRADD可降低这种亡,揭示了斯特里赫尼精液诱导的毒性潜在的治疗标.

科学领域:

毒理学毒理学毒理学
药理学药理学是指药理学的学科.
分子生物学分子生物学

背景情况:

来自Strychnos nux-vomica L的Strychni Semen具有药用价值,但表现出严重的毒性,特别影响中枢神经系统和泌尿系统.
了解斯特里克尼精液诱导的毒性背后的机制对于减轻其不良影响和安全地探索其治疗潜力至关重要.

研究的目的:

阐明斯特里赫尼精液及其主要类成分布鲁辛和斯特里赫尼因诱导的毒性分子机制.
研究TRADD介导的MAPK和NF-κB通路在斯特里奇尼精液诱导的细胞亡中的作用.

主要方法:

用Strychni Semen (SS),brucine (B),strychnine (S) 或抑制剂Apostatin-1治疗HK-2细胞.
分析了炎症性细胞因子 (IL-6,IL-1β,TNF-α),KIM-1和与通路相关的蛋白质 (TRADD,JNK,p38,caspase-3) 的表达.
网络药理学被用来预测可能涉及斯特里奇尼精液诱导的毒性途径.

主要成果:

斯特里奇尼精液及其类化合物激活了MAPK和NF-κB信号级联中的JNK和p38通路.
在HK-2细胞中,通过对酶-3的上调促进了亡,同时增加了IL-6,IL-1β,TNF-α和KIM-1的产生.
阿波斯塔丁-1治疗对抗了SS诱导的亡和降低了细胞因子的产生,表明TRADD在毒性机制中的作用.

结论:

斯特里克尼精液及其类化合物通过TRADD介导的MAPK和NF-κB通路的激活诱导HK-2细胞亡和细胞毒性.
针对TRADD提出了一个潜在的策略,以减轻斯特里奇尼精液及其成分的毒作用.

关键词:

这就是MAPKK的意思.在 NF-κBB 中.毒性毒性毒性斯特里赫尼的精子贸易贸易贸易

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