空间解析的新陈代谢和网络药理学揭示了提取物 D 在Pleuropterus multiflorus中的毒性机制
Haiyan Jiang1, Ying Wang2, Xiaoyan Duan1
1New Drug Safety Evaluation Center, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
斑点多花提取物D (PM-D) 通过破坏能量,脂质和核酸代谢而导致脏损伤. 这项研究揭示了PM-D.
科学领域:
- 毒理学 毒理学 毒理学
- 药理学 药理学 是一个学科.
- 代谢学 代谢学 代谢学
背景情况:
- 传统中医药Pleuropterus multiflorus (PM) 已知对肝脏有毒.
- 微粒的毒性 (毒性),特别是微粒提取物D (PM-D) 的毒性,尚未得到研究.
- 之前的工作确定PM-D是肝毒性的.
研究的目的:
- 为了研究PM-D诱导的毒性机制.
- 探索PM-D毒性所涉及的分子标和代谢途径.
主要方法:
- 网络药理学确定了核心基因 (BCL2,HSP90,ESR1,CTNNB1) 并丰富了PI3K/AKT通路.
- 空间解析的代谢量揭示了脏中异质的代谢物分布.
- 给小鼠服用PM-D (2g/kg) 持续7天,并评估功能和病理.
主要成果:
- 服用PM-D会增加脏生化指数,并导致病态脏损伤.
- 代谢分析表明,在α-烯酸,烯酸,胺酸代谢,肉氨酸合成和分支链脂肪酸氧化中,有丰富的途径.
- 毒性机制包括由于能量,脂质和核酸代谢失调而导致的氧化应激和亡.
结论:
- PM-D诱导显著的毒性.
- 网络药理学和代谢学阐明了PM-D毒性的分子和代谢基础.
- 这些发现为进一步研究PM-D的毒性提供了基础.
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