Huperzine A ameliorates damage induced by acute myocardial infarction in rats through antioxidant, anti-apoptotic and anti-inflammatory mechanisms

Abstract

Huperzine A (HupA), an alkaloid used in traditional Chinese medicine and isolated from Huperzia serrata, has been shown to possess diverse biological activities. The present study was undertaken to evaluate the cardioprotective potential of HupA in myocardial ischemic damage using a rat model of acute myocardial infarction. HupA significantly diminished the infarct size and inhibited the activities of myocardial enzymes, including creatine kinase (CK), the MB isoenzyme of creatine kinase (CK-MB), lactate dehydrogenase (LDH) and cardiac troponin T (cTnT). A significantly reduced activity of malondialdehyde (MDA) and elevated activities of superoxide dismutase (SOD), of the non-enzymatic scavenger enzyme, glutathione (GSH), as well as of glutathione peroxidase (GSH-PX) were found in the HupA-treated groups. Furthermore, decreased protein levels of caspase-3 and Bax, and increased levels of Bcl-2 were observed in the infarcted hearts of the rats treated with various concentrations of HupA. In addition, treatment with HupA markedly inhibited the expression of the nuclear factor-κB (NF-κB) subunit p65, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). These findings suggest that the cardioprotective potential of HupA is associated with its antioxidant, anti-apoptotic and anti-inflammatory properties in acute myocardial infarction in rats.

The effects of acetylcholinesterase inhibitors on the heart in acute myocardial infarction and heart failure: From cells to patient reports

“…27 In that study, Huperzine A attenuated apoptotic markers (ie caspase-3 level and activity, Bax [BCL2-associated X] protein) and increased the expression of an anti-apoptotic marker (ie Bcl-2 protein), leading to reduced apoptosis, infarct size and cardiac injury after MI. 27 In that study, Huperzine A attenuated apoptotic markers (ie caspase-3 level and activity, Bax [BCL2-associated X] protein) and increased the expression of an anti-apoptotic marker (ie Bcl-2 protein), leading to reduced apoptosis, infarct size and cardiac injury after MI.…”

“…The anti-arrhythmogenic effect of AChE inhibitors are summarized in Table 2. 3.3 | AChE inhibitors reduced oxidative stress, apoptosis, inflammation, and infarct size in rats with MI and heart failure Cardioprotective effects of AChE inhibitors through reduction in oxidative stress, apoptosis, inflammation, infarct F I G U R E 1 Schematic representation of the possible mechanisms of acetylcholine synthesis. 27 Similarly, pyridostigmine diminished protein oxidation and enhanced the antioxidant system in rats with AMI. Furthermore, donepezil has been shown to enhance ChAT and ACh production in cardiomyocytes independent of acetylcholinesterase (AChE) inhibition or mAChRs.…”

“…103 In the same way, donepezil enhanced the survival pathway through increasing the pAkt/Akt ratio, leading to improved cardiac function and survival of chronic heart failure mice. 27,31,32,37,38 However, there are inconsistencies as some reports demonstrate that AChE inhibitors may not attenuate infarct size after MI. 105 As infarct size plays an important role in cardiac remodelling and function, 106 it is promising that AChE inhibitors have been shown to attenuate infarct size and cardiac dysfunction in various models.…”

“…21 However, further clinical studies are needed to warrant its clinical use. [26][27][28][29][30][31][32][33][34][35][36][37][38][39] Despite its potential clinical benefits for CVDs patients, the role of AChE inhibitors in AMI and heart failure remediation remains unclear. 22,23 Use of AChE inhibitors is a non-invasive intervention which increases the parasympathetic activity.…”

“…25 Previous studies have shown that cholinergic stimulation by AChE inhibitors attenuated sympathovagal imbalance, ischaemic-induced arrhythmia, inflammation, oxidative stress and apoptosis in myocardial infarction (MI) rats. [26][27][28][29][30][31][32][33][34][35][36][37][38][39] Despite its potential clinical benefits for CVDs patients, the role of AChE inhibitors in AMI and heart failure remediation remains unclear. This article comprehensively reviews the effects of AChE inhibitors on the heart in AMI and heart failure from in vitro and in vivo studies to clinical reports.…”