Acacetin Protects Myocardial Cells against Hypoxia-Reoxygenation Injury through Activation of Autophagy

Abstract

Ischemic heart disease is a leading cause of mortality and morbidity worldwide. We previously demonstrated that acacetin protects against myocardial ischemia reperfusion injury in rats, although the underlying mechanism remains to be elucidated. In the present study, we investigated the effects of acacetin on autophagy during hypoxia/reoxygenation (H/R) injury by exposing H9c2 myocardial cells to H/R with or without acacetin pretreatment during hypoxia. Our results show that acacetin significantly increased cell viability in a dose-dependent manner, enhanced antioxidant capacity, and suppressed protein apoptosis of rat cardiomyocytes H9c2 cells following H/R injury. In addition, lentiviral infection of H9c2 cardiomyocytes revealed that acacetin pretreatment significantly enhanced the fluorescence intensity of autophagy proteins Beclin 1, LC3-II, and p62. These results indicate that acacetin protected H9c2 cardiomyocytes from H/R damage by enhancing autophagy. Moreover, we found that application of acacetin increased activation of the PI3K/Akt signaling pathway, whereas cotreatment with the PI3K inhibitor LY294002 reversed the inhibition of apoptosis and autophagy induced by acacetin. In conclusion, acacetin mitigated H/R injury by promoting autophagy through activating the PI3K/Akt/mTOR signaling pathway.

Acacetin Alleviates Cardiac Fibrosis via TGF-β1/Smad and AKT/mTOR Signal Pathways in Spontaneous Hypertensive Rats

“…Another study found that the improved effects were mediated by activating the PI3K/AKT/mTOR signaling pathway [8]. Furthermore, acacetin protects cardiomyocytes against hypoxia/reoxygenation injury via AMPKmediated Nrf2 activation [14].…”

“…Recently, studies have demonstrated that acacetin can improve cardiac hypoxia/reoxygenation injury via reducing lipid peroxidation and enhancing antioxidant capacity [13]. Another study found that the improved effects were mediated by activating the PI3K/AKT/mTOR signaling pathway [8]. Furthermore, acacetin protects cardiomyocytes against hypoxia/reoxygenation injury via AMPK-mediated Nrf2 activation [14].…”

“…Acacetin prevented atrial fibrillation by selectively inhibiting atrial repolarization potassium currents in dogs [6]. Furthermore, acacetin improved ischemia/reperfusion and hypoxia-reoxygenation-induced cardiac injury [7, 8] and ameliorated doxorubicin-induced cardiomyopathy by activating sirt1-mediated AMPK/Nrf2 signal pathway [9]. Acacetin also alleviated endothelial dysfunction and reduced aortic fibrosis in insulin-resistant spontaneous hypertensive rat (SHR) by decreasing inflammatory factor release and recovering vasodilatory function through estrogen signaling pathway [10].…”

Acacetin as a Potential Protective Compound against Cardiovascular Diseases

“…Further studies have confirmed that the antioxidant, anti-inflammatory, and antiapoptotic effects of acacetin on cells are mediated by AMPK-mediated Nrf2 activation [ 35 ]. Interestingly, a recent study demonstrated that autophagy is involved in the process of alleviation of myocardial hypoxia/reoxygenation injury by acacetin; that is, acacetin enhanced autophagy through activating the PI3K/Akt/mTOR pathway [ 36 ].…”

Acacetin Inhibits Cell Proliferation and Induces Apoptosis in Human Hepatocellular Carcinoma Cell Lines

“…To identify natural-source-derived pharmacological drugs that could be useful for cancer therapy by targeting STAT3 activation pathways, focus has been placed on acacetin isolated from plants, such as Tunera diffusa, Propolis, Dracocephalum moldavica, Betula pendula, Robinia pseudoacacia, Flos Chrysanthemi Indici, Chrysanthemum, Safflower, Calamintha, and Linaria species [ 16 , 17 ]. As a natural flavonoid compound, acacetin (5,7-dihydroxy-4′-methoxyflavone) has antioxidative and anti-inflammatory effects and has exhibited extensive therapeutic effects on numerous cancers [ 17 , 18 , 19 , 20 , 21 ]. However, the elaborate molecular mechanisms through which ACN brings about these effects and its potential in vitro efficacy on HCC progression remain unclear.…”