Fan Hao, Wang Li, Zhang Ze-Kun, Wu Ping-Ping, He Yu-Pei, Chen Le-Yi, Wang Qian, Zhang Cui-Xian
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Research Center of Integrative Medicine, School of Basic Medical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Bioengineering (Basel). 2023 Jul 5;10(7):805. doi: 10.3390/bioengineering10070805.
Two new disubstituted maleimides, aspergteroids G-H (-), and two trisubstituted butenolides aspergteroids I-J (-), along with four known analogs, were isolated and structurally identified from the fermentation extract of soft-coral-associated symbiotic and epiphytic fungus EGF7-0-1. The structures of the new compounds were established mainly via spectroscopic data analyses, and their absolute configurations were determined via X-ray diffraction analysis and comparison of the calculated and experimental electronic circular dichroism. Myocardial protection assays showed that compounds , , , and possess protective effects against tert-butyl hydroperoxide (TBHP)-induced H9c2 (rat myocardial cells) apoptosis at low concentrations. Based on the analyses of the protein-protein interaction (PPI) network and Western blotting, compound may inhibit the apoptosis and inflammatory response of cardiomyocytes after TBHP induction and improve the antioxidant capacity of cardiomyocytes. We speculate that the anti-inflammatory response of compound is suppressed by the glycogen synthase kinase-3 beta (GSK-3β), downregulated by the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome activation, and suppressed by the expression of cysteinyl aspartate specific proteinase-3 (caspase-3) and B-cell lymphoma-2 associated X protein (Bax).
从软珊瑚共生及附生真菌EGF7-0-1的发酵提取物中分离并鉴定出两种新的二取代马来酰亚胺类化合物aspergteroids G-H (-),两种三取代丁烯内酯类化合物aspergteroids I-J (-),以及四种已知类似物。新化合物的结构主要通过光谱数据分析确定,其绝对构型通过X射线衍射分析以及计算和实验电子圆二色性的比较来确定。心肌保护试验表明,化合物、、、在低浓度时对叔丁基过氧化氢(TBHP)诱导的H9c2(大鼠心肌细胞)凋亡具有保护作用。基于蛋白质-蛋白质相互作用(PPI)网络分析和蛋白质印迹法,化合物可能抑制TBHP诱导后心肌细胞的凋亡和炎症反应,并提高心肌细胞的抗氧化能力。我们推测,化合物的抗炎反应受到糖原合酶激酶-3β(GSK-3β)的抑制,通过NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体激活而下调,并受到半胱天冬酶-3(caspase-3)和B细胞淋巴瘤-2相关X蛋白(Bax)表达的抑制。