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

Abstract

Background/Aims: Epoxyeicosatrienoic acids (EETs) are cytochrome P450 epoxygenase (CYP) metabolites of arachidonic acid and have multiple cardiovascular effects. Ophiopogonin D (OP-D) is an important effective monomeric component in Shenmai injection (SM-I). Both have been reported to have a variety of biological functions, including anti-inflammatory, anti-oxidant, and anti-apoptotic effects. We previously demonstrated that OP-D–mediated cardioprotection involves activation of CYP2J2/3 and enhancement of circulating EETs levels in vitro and can be developed as a novel drug for the therapy of myocardial ischemia-reperfusion (MI/R) injury. We therefore hypothesized that the protective effects of OP-D and SM-I against MI/R injury are associated with increased expression of CYP2J3 and enhanced circulating 11,12-EET levels in vivo. Methods: A rat model of MI/R injury was generated by ligation of the left anterior descending coronary artery for 40 min, followed by reperfusion for 2 h to determine the protective effects and potential mechanisms of OP-D and SM-I. Electrocardiogram and ultrasonic cardiogram were used to evaluate cardiac function; 2,3,5-triphenyltetrazolium chloride was used to measure myocardial infarct size; hematoxylin and eosin staining and transmission electron microscopy were used to observe the morphology of myocardial tissue; and the expression of related proteins in the mechanistic study was observed by western blot analysis. Results: We found that OP-D and SM-I exert protective effects on MI/R injury, including regulation of cardiac function, reduction of lactate dehydrogenase and creatine kinase production, attenuation of myocardial infarct size, and improvement of the recovery of damaged myocardial structures. We found that OP-D and SM-I activate CYP2J3 expression and increase levels of circulating 11,12-EET in MI/R-injured rats. Conclusion: We tested the hypothesis that the cardioprotective effects of OP-D and SM-I on MI/R injury are associated with increased expression of CYP2J3 and enhanced circulating 11,12-EET levels in rats. Taken together, our results show that the effects of OP-D and SM-I were also mediated by the activation of the PI3K/Akt/eNOS signaling pathway, while inhibition of the NF-κB signaling pathway and antioxidant and anti-apoptotic effects were involved in the cardioprotective effects of OP-D and SM-I.

Protective Effect and Mechanism of Traditional Chinese Medicine on Myocardial Ischemia Reperfusion Injury

“…Ginsenoside Rb1 was able to protect cardiomyocytes by activating the PI3K/Akt/mTOR pathway via phosphorylation as shown by Western blot analysis, which was abolished after the application of rapamycin [30]. Ophiopogonin D has multiple biological functions, and studies have shown its ability to inhibit apoptosis by regulating the caspase pathway through arachidonic acid metabolites [27]. Similar to ophiopogonin D, withaferin A improves I/R-injured H9C2 cells viability by inhibiting caspase activity [24].…”

Investigation of cardiovascular protective effect of Shenmai injection by network pharmacology and pharmacological evaluation

“…Moreover, it has been reported that Akt activation improved contractile function of failing hearts [37,38]. Shreds of evidence have shown that SMI and its ingredients ophiopogonin D activated PI3K/Akt signaling pathway in myocardial ischemia-reperfusion injury [39]. Our previous study suggested that ginsenoside Rg3 could promote cell viability and attenuate DOX-induced oxidative damage and apoptosis through Akt activation [40].…”

Effect of Traditional Chinese Medicine on the Cardiovascular Diseases

“…This molecule has been shown to have anti-apoptotic, antioxidant, and anti-inflammatory properties ( Huang et al, 2015 ; You et al, 2016 ). The left anterior descending coronary artery was also occluded in rats to create the MI/R model for studying the antioxidants OP-ED and SM-I ( Huang et al, 2018 ). An infarct is reduced in size, and heart architecture is improved by using OP-ED and SEM-I to protect cardiac function from MI/R.…”