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TJ507 中的生物活性吲哚生物碱可改善肝缺血/再灌注损伤。

Bioactive Indole Alkaloid from TJ507 That Ameliorates Hepatic Ischemia/Reperfusion Injury.

机构信息

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

Key Laboratory of Organ Transplantation, Ministry of Education; NHC Key Laboratory of Organ Transplantation; Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan 430030, China.

出版信息

J Nat Prod. 2023 Aug 25;86(8):2059-2064. doi: 10.1021/acs.jnatprod.3c00251. Epub 2023 Aug 10.

Abstract

Hepatic ischemia/reperfusion injury (IRI) is a major factor contributing to the failure of hepatic resection and liver transplantation. As part of our ongoing investigation into bioactive compounds derived from fungi, we isolated eight indole alkaloids (-) from the endophytic fungus TJ507. Among these alkaloids, one previously undescribed compound, amoenamide D (), was identified. The planar structure of was elucidated by extensive spectroscopic analysis, including HRESIMS and NMR spectra. The absolute configuration of was elucidated by using electronic circular dichroism calculations. Notably, in the CoCl-induced hepatocyte damage model, notoamide Q () exhibited significant anti-hypoxia injury activity. Furthermore, in a murine hepatic ischemia/reperfusion injury model, treatment with prevents IRI-induced liver damage and hepatocellular apoptosis. Consequently, might serve as a potential lead compound to prevent hepatic ischemia/reperfusion injury.

摘要

肝缺血/再灌注损伤(IRI)是导致肝切除和肝移植失败的主要因素。作为我们对真菌来源的生物活性化合物的持续研究的一部分,我们从内生真菌 TJ507 中分离出了八种吲哚生物碱(-)。在这些生物碱中,我们鉴定了一种以前未描述的化合物,阿默酰胺 D()。通过广泛的光谱分析,包括 HRESIMS 和 NMR 谱,阐明了的平面结构。通过使用电子圆二色性计算阐明了的绝对构型。值得注意的是,在 CoCl 诱导的肝细胞损伤模型中,notoamide Q()表现出显著的抗缺氧损伤活性。此外,在小鼠肝缺血/再灌注损伤模型中,用 治疗可预防 IRI 引起的肝损伤和肝细胞凋亡。因此, 可能作为预防肝缺血/再灌注损伤的潜在先导化合物。

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