<p>Protective Effect Of Vasicine Against Myocardial Infarction In Rats Via Modulation Of Oxidative Stress, Inflammation, And The PI3K/Akt Pathway</p>

Abstract

BackgroundMyocardial infarction is the leading cause of damage to the heart and is classified as a major cause of death related to cardiovascular disease. In the present study, we intended to investigate the protective effect of vasicine (VAS) against myocardial infarction in rats, and its mechanism.MethodsMyocardial infarction was induced by isoproterenol (ISO, 100 mg/kg) at an interval of 24 h for 2 days. Different doses of VAS (2.5, 5, and 10 mg/kg body weight) were administered to the rats. The effect of VAS on oxidative stress markers such as, myocardial necrosis, myocardial ability and infarct volume, inflammatory cytokines, membrane-bound myocardial enzymes, and histopathological changes was investigated. Western blot analysis was also conducted to analyze the effect of VAS on autophagy (PI3K/Akt) and apoptosis (Bcl-2, Bax, and caspase-3). The number of apoptotic cells in the different groups was also identified using TUNEL.ResultsResults suggested that VAS causes reduction in myocardial necrosis by reduction of elevated LDH, CK-MB, and TnT levels. It also causes augmentation of left ventricular systolic pressure (LVSP) and myocardial contractility as determined in terms of +dp/dtmax and –dp/dtmax. Furthermore, VAS causes reduction of TNF-α and IL-6 levels. VAS also improved cardiac function via enhancing posterior wall thickness of the LV with concurrent increase in the mass of LV. In the present study, VAS caused activation of phosphorylated PI3K (p-PI3K) and phosphorylated Akt (p-Akt) in a dose-dependent manner. Furthermore, VAS suppressed apoptosis when tested on animals suffering from ISO-induced MI, by decreasing the expression of cleaved Caspase-3 and Bax while increasing the expression of Bcl-2.ConclusionIn conclusion, vasicine has a protective effect against MI in vivo, through inhibiting oxidative stress, inflammation and excessive autophagy, to suppress apoptosis via activation of the PI3K/Akt/mTOR signaling pathway.

Protective Effect of Geraniol on Oxidative, Inflammatory and Apoptotic Alterations in Isoproterenol-Induced Cardiotoxicity: Role of the Keap1/Nrf2/HO-1 and PI3K/Akt/mTOR Pathways

“…The ISO-induced MI group showed numerous ECG alterations, presence of an infarct area, increase in the levels of cardiac enzymes, moderate-to-severe myocardial necrosis, edema, and extensive immune cells infiltration. It has been previously reported that ISO causes detrimental cardiac effects, including necrosis, apoptosis, mitochondrial modifications, oxidative injury, and inflammatory cell infiltration, comparable to what is observed in the ischemic human heart [ 8 , 23 , 25 , 26 ]. Compared to ISO-challenged animals, geraniol pretreatment led to a size reduction of the infarct region, attenuation of cardiac indicator enzymes, as well as diminished myocardial necrosis, edema, and immune cells infiltration.…”

“…Autophagy is a type II cell death mechanism, which is known to be involved in the pathophysiological process of MI; therefore, the modulation of autophagy may be considered as a therapeutic strategy for MI [ 26 ]. Previous studies established that compounds that modulate PI3K/Akt signaling can exhibit cardioprotective actions [ 8 , 26 ]. Akt phosphorylation has been found to prevent apoptosis and promote cell survival in the ischemic heart [ 5 ].…”

“…These results indicate that geraniol caused the activation of PI3k/Akt in a dose-dependent manner and suggest that it may have modulated the myocardial autophagy by this mechanism. In previous studies, numerous drugs have demonstrated cardioprotective activity through activation of the PI3K/Akt pathway; examples include Paeonol and danshensu [ 5 ], Vasicine [ 26 ], Qi-Li-Qiang-Xin (a traditional Chinese medication) [ 28 ], and Levosimendan [ 29 ]. Activation of the PI3K/Akt/mTOR pathway also protected against myocardial injury by diminishing oxidative stress, limiting the inflammatory cascade, and deterring apoptosis in vivo and in vitro [ 8 ].…”

A possible underlying mechanism behind the cardioprotective efficacy of tangeretin on isoproterenol triggered cardiotoxicity via modulating PI3K/Akt signaling pathway in a rat model

“…Copious amount of evidence infers that any agent which could modulate or regulate PI3K/Akt signaling pathway may display myocardial protection (cardioprotective) by inhibiting oxidative stress and apoptosis (Jiang et al., 2019; Yang et al, 2019). Hence, we speculate that TAN might also, modulate PI3K/Akt pathway and thus favor cardioprotective activity against the ISP‐induced MI model.…”

“…Recently, Lu et al (2018) confirmed the cardioprotective activity of TAN against heart failure (MI) in the rat model, but they failed to explore the in‐depth molecular mechanism. Copious studies have demonstrated that any agent in which modulation or regulation PI3K/Akt signaling pathway might involve in myocardial protection (cardioprotective) by inhibiting oxidative stress and apoptosis (Jiang, Zhang, Ding, & Li, 2019; Yang et al, 2019). Hence, we hypothesize that TAN might also, modulate PI3K/Akt pathway and thus favor cardioprotective activity against the isoproterenol (ISP)‐induced MI model.…”