Hu Hong, Li Yanhui, Shi Zhengyi, Zhao Xiangli, Lan Xueqi, Wu Meng, Tao Bo, Zhang Yeting, Huang Xinye, Bu Pengfei, Guo Yi, Tan Xiaosheng, Qi Changxing, Zhang Yonghui
Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, People's Republic of China.
Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People's Republic of China.
Bioorg Chem. 2023 Jun;135:106530. doi: 10.1016/j.bioorg.2023.106530. Epub 2023 Apr 8.
Hepatic ischemia/reperfusion injury is a major cause of hypohepatia after surgical procedures such as hypovolemic shock, transplantation, and so on. In our continuous study of bioactive natural products from fungus, eight ergosterol-type sterides (1-8), including two undescribed compounds, sterolaspers A (1) and B (2), were isolated from Aspergillus sp. TJ507. Structure elucidation was accomplished by extensive spectroscopic analysis and comparison with the reported NMR data as well as X-Ray single crystal diffraction tests. Activity screen of these isolates showed 5α-stigmast-3,6-dione (3) possessing anti-hypoxia injury effects against CoCl-induced hypoxia damage in hepatocytes. More importantly, compound 3 could improve liver function, alleviate liver damage, and restrain the hepatocellular apoptosis in hepatic ischemia/reperfusion injury murine model. As such, this ergosterol-type steride, 5α-stigmast-3,6-dione (3), might serve as lead structure for the development of novel hepatoprotective agents in the clinical treatment of hepatic ischemia/reperfusion injury.
肝缺血/再灌注损伤是诸如低血容量性休克、移植等外科手术后肝功能减退的主要原因。在我们对真菌来源的生物活性天然产物的持续研究中，从曲霉属TJ507中分离出了8种麦角甾醇型甾体化合物（1-8），其中包括2种未描述的化合物，即麦角甾醇A（1）和B（2）。通过广泛的光谱分析、与已报道的核磁共振数据进行比较以及X射线单晶衍射测试完成了结构解析。这些分离物的活性筛选表明，5α-豆甾-3,6-二酮（3）对氯化钴诱导的肝细胞缺氧损伤具有抗缺氧损伤作用。更重要的是，化合物3可以改善肝功能、减轻肝损伤，并抑制肝缺血/再灌注损伤小鼠模型中的肝细胞凋亡。因此，这种麦角甾醇型甾体化合物5α-豆甾-3,6-二酮（3）可能作为开发新型肝保护剂用于肝缺血/再灌注损伤临床治疗的先导结构。
