Protective effect of ligustrazine against myocardial ischaemia reperfusion in rats: The role of endothelial nitric oxide synthase

Abstract

1. The aim of the present study was to determine whether ligustrazine (2,3,5,6-tetramethylpyrazine; TMP) exerts a cardioprotective effect during myocardial ischaemia reperfusion (IR), and to investigate the underlying mechanisms and the role of endothelial nitric oxide synthase (eNOS) in cardioprotection. 2. Sprague-Dawley rats were divided into a sham group and five IR groups: IR control, TMP pretreated, TMP + wortmannin (a phosphatidylinositol 3-kinase (PI3K) inhibitor), N(G) -nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor) and TMP + L-NAME. IR was produced by 35 min of regional ischaemia followed by 120 min of reperfusion. Myocardial infarct size, oxidative stress, myocardial apoptosis, nitric oxide (NO) production, and expression of phosphorylated protein kinase B (Akt) and eNOS were measured. 3. TMP markedly decreased infarct size and attenuated myocardial apoptosis, as evidenced by a decrease in the apoptotic index and reduced caspase-3 activity. TMP treatment caused a marked increase in NO production. Cotreatment with wortmannin or L-NAME completely blocked the TMP-induced NO increase. TMP induced phosphorylation of Akt at Ser 473 (1.61 ± 0.18 vs 0.79 ± 0.10 in the IR control group) and phosphorylation of eNOS at Ser1177 (1.87 ± 0.33 vs 0.94 ± 0.22 in the IR control group). Wortmannin abrogated the phosphorylation of Akt and eNOS induced by TMP. 4. These data suggest that ligustrazine has anti-apoptotic and cardioprotective effects against myocardial IR injury and that it acts through the PI3K/Akt pathway. In addition, the phosphorylation of eNOS with subsequent NO production was found to be an important downstream effector that contributes significantly to the cardioprotective effect of TMP.

Ophiopogonin D Reduces Myocardial Ischemia-Reperfusion Injury via Upregulating CYP2J3/EETs in Rats

“…Our results showed that OP-D and SM-I could attenuate MI/R injury by upregulating eNOS via its phosphorylation, indicating an increase in eNOS activity in MI/ R-injured rats. Many studies have reported that the PI3K/Akt/eNOS signaling pathway plays a role in MI/R damage [40,41]. The results of the present study support our hypothesis that the cardioprotective effects of OP-D and SM-I in rats can be attributed to their ability to increase the phosphorylation of eNOS through the PI3K/Akt pathway, but more data are needed to confirm the idea.…”

Assessment of the Anti-anginal Effect of Tetramethylpyrazine Using Vasopressin-Induced Angina Model Rats

“…Tetramethylpyrazine has been shown to stimulate Ca 2+ -activated potassium current, 4) cyclic adenosine monophosphate production, 5) and the endothelial nitric oxide synthase 6) in addition to Ca 2+ channel blockade.…”

“…6) Moreover, pretreatment of tetramethylpyrazine was shown to ameliorate a vasoconstrictor terlipressin-induced decrease of cardiac index in portal hypertensive rats. 7) However, in vivo experimental evidence for empirically known clinical efficacy of tetramethylpyrazine is still limited.…”

“…was infused over 1 min. The dose of tetramethylpyrazine in this study was determined by previous experimental studies [2][3][4][5][6][7] as well as clinical experiences as a traditional Chinese medicine.…”

Proliferative Activity and Neuroprotective Effect of Ligustrazene Derivative by Irritation of Vascular Endothelial Growth Factor Expression in Middle Cerebral Artery Occlusion Rats

“…As one of the major effective ingredients of Rhizoma Chuanxiong ligustrazine (2,3,5,6-tetramethylpyrazine, TMP) has been widely used in the treatment of ischemic stroke and cerebrovascular disease in China for many years [6] Previous studies have shown various pharmacological activities of TMP, such as antimyocardial ischemia, anti-cerebral ischemia, inhibiting platelet aggregation, protecting vascular endothelial, etc [7][8][9][10][11]. To further improve the neuroprotective property of TMP, we decided to undertake a study of a novel series of TMP derivatives based on the principles of hybridization and prodrug design in medicinal chemistry and acquired compounds with pharmacologically additive or synergetic e ects [12][13][14].…”