Cardioprotection of tilianin ameliorates myocardial ischemia-reperfusion injury: Role of the apoptotic signaling pathway

Abstract

Our previous research demonstrated that tilianin protects the myocardium in a myocardial ischemia reperfusion injury (MIRI) rat model and has prominent pharmacological potential as a cardiovascular drug. Our study aimed to investigate the molecular signaling implicated in the improvement of myocardial survival induced by tilianin, a flavonoid antioxidant. Tilianin (2.5, 5, and 10 mg/kg/d) or saline was orally administered to rats for 14 days. On the 15th day, ischemia was induced by ligating the left anterior descending artery for 45 min, followed by 4 h of reperfusion. The levels of MIRI-induced serum myocardial enzymes and cardiomyocyte apoptosis as well as infarct size were examined to assess the cardioprotective effects. Cardiac tissues were collected for western blot analyses to determine the protein expression of anti-apoptotic signaling molecules. In MIRI-treated rats, our results revealed that pre-administration of high dose-tilianin the reduced release of LDH, MDA, and CK-MB and increased the plasma SOD level, and significantly attenuated the infarct size. Western blot analysis showed that a remarkable rise in expression of Bcl-2 and XIAP, and decline in expression of Bax, Smac/Diablo, HtrA2/Omi, cleaved caspase-3, caspase-7 and caspase-9 was observed in the myocardium. The apoptosis index of cardiomyocytes further supports the cardioprotective effect of tilianin. Additionally, compared with the MIRI model group, pretreatment with high dose-tilianin group upregulated phosphorylated Akt and PI3K. In contrast, using the PI3K inhibitor LY294002 to block Akt activation effectively inhibited the protective effects of tilianin against MIRI. Tilianin pretreatment was beneficial for activating the PI3K/Akt signaling pathway and inhibiting myocardial apoptosis.

Tilianin Extracted From Dracocephalum moldavica L. Induces Intrinsic Apoptosis and Drives Inflammatory Microenvironment Response on Pharyngeal Squamous Carcinoma Cells via Regulating TLR4 Signaling Pathways

“…Tilianin is the major effective component of the total flavonoid extract from D. moldavica (Zeng et al, 2016). Tilianin has been reported to have neuroprotective and cardioprotective effects in the treatment of cardiovascular and cerebrovascular diseases (Zeng et al, 2018;Jiang et al, 2019). Moreover, in previous studies, it was reported that tilianin displayed anti-tumor effects in human lung adenocarcinoma and anti-angiogenesis effects based on VEGF-A (Meng, 2018;Meng et al, 2018).…”

The myocardial protective effect of monosodium phosphate cardioplegia in cardiopulmonary bypass in infants with an atrial septal defect

“…LDH, CPK, AST, CTnI, and CK-MB are key myocardial enzymes used to estimate the degree of myocardial injury. [ 17 ] The results of this study showed that cardiac cardioplegia containing sodium creatine phosphate effectively reduced myocardial enzymes, such as LDH, CPK, AST, CTnI, and CK-MB, in infants with an atrial septal defect, indicating reduced myocardial damage during cardiopulmonary bypass. ATP, ADP, AMP, and CP are the key myocardial energetic indexes.…”

MiR‐134‐5p targeting XIAP modulates oxidative stress and apoptosis in cardiomyocytes under hypoxia/reperfusion‐induced injury

“…Furthermore, several drugs targeting XIAP displayed prominent pharmacological potential as a cardiovascular drug after MI/R. Zeng et al 28 revealed that tilianin pre-administration ameliorated MI/R injury through repressing oxidative response and apoptosis including the reduction of LDH, MDA, and CK-MB release, and the increase of SOD and XIAP expression, thus significantly attenuated the infarct size. Calderon-Sanchez et al 29 stated that Urocortin-1 administration accompanied with upregulated XIAP, Bad and CD40-ligand increased cell survival, and inhibited LDH release in MI/R damage through Epac2 and ERK signaling pathways.…”

“…However, the role of miR-134-5p in other cell processes like inflammation and autophagy remains to be further uncovered, as well as its involved signaling pathways such as ERK 29,30 and PI3K/ Akt. 28 Furthermore, better understanding of the molecular mechanisms of miR-134-5p in AMI need to be urgently addressed prior to be an attractive therapeutic target.…”