Department of Pharmacology, School of Pharmaceutical Sciences, Shandong University.
Department of Pharmacy, Affiliated Hospital of Weifang Medical University.
Biosci Trends. 2017 Nov 20;11(5):557-564. doi: 10.5582/bst.2017.01111. Epub 2017 Oct 16.
Cardiomyocyte nutrient deprivation is a common clinical event that mediates various cardiac ischemic processes and is associated with autophagy activation and cell survival or death. Luteolin-7-O-glucoside (LUTG) was one of the flavonoid glycosides isolated from Dracocephalum tanguticum. Previous research had showed that LUTG pretreatment had significant protective effects against doxorubicin-induced cardiotoxicity. However, whether LUTG could protect cardiomyocytes from starvation-induced injury was not clear. In this study, cardioprotection and mechanisms of LUTG against starvation-induced injury were investigated in vitro. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-tetrazolium bromide (MTT) assay showed starvation-induced autophagy is a homeostatic and protective response for H9c2 cell survival. LUTG could protect against injury induced by starvation in H9c2 cells. Acridine orange (AO) staining showed that pretreatment with LUTG enhanced lysosomal autophagy. Western blotting indicated that LUTG enhanced autophagy by down-regulating the expression of phospho-extracellular signal regulated kinase1/2 (p-ERK), phospho-protein kinase B (p-Akt) and phospho-mammalian target of rapamycin (p-mTOR). These results suggest that LUTG might act as a promising therapeutic agent for preventing starvation-induced cardiotoxicity by upregulation of autophagy through the Akt/mTOR and ERK signal pathway.
心肌细胞营养剥夺是一种常见的临床事件，介导各种心脏缺血过程，并与自噬激活和细胞存活或死亡有关。木犀草素-7-O-葡萄糖苷（LUTG）是从Dracocephalum tanguticum 中分离得到的一种类黄酮糖苷。先前的研究表明，LUTG 预处理对阿霉素诱导的心肌毒性具有显著的保护作用。然而，LUTG 是否能保护心肌细胞免受饥饿诱导的损伤尚不清楚。在这项研究中，研究了 LUTG 对体外饥饿诱导损伤的心脏保护作用及其机制。3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-四唑溴盐（MTT）测定表明，饥饿诱导的自噬是 H9c2 细胞存活的一种体内平衡和保护反应。LUTG 可以保护 H9c2 细胞免受饥饿引起的损伤。吖啶橙（AO）染色表明，LUTG 预处理增强了溶酶体自噬。Western blot 表明，LUTG 通过下调磷酸化细胞外信号调节激酶 1/2（p-ERK）、磷酸化蛋白激酶 B（p-Akt）和磷酸化雷帕霉素靶蛋白（p-mTOR）的表达来增强自噬。这些结果表明，LUTG 可能通过 Akt/mTOR 和 ERK 信号通路上调自噬，作为预防饥饿诱导的心肌毒性的一种有前途的治疗剂。
