Oxypaeoniflorin improves myocardial ischemia/reperfusion injury by activating the Sirt1/Foxo1 signaling pathway

Abstract

Myocardial ischemia/reperfusion (MI/R) injury is a leading cause of damage to cardiac tissues and is associated with high mortality and disability rates worldwide. Oxypaeoniflorin (OPA) has been found to be the main constituent of Paeonia veitchii Lynch. This study was conducted to explore the effect of OPA on MI/R injury and its potential mechanism. An in vivo MI/R injury model was established by transient coronary ligation in BALB/c mice, and an in vitro hypoxia/reoxygenation (H/R) injury model was established with rat cardiomyocyte H9c2 cells. Echocardiographic assessments demonstrated that OPA significantly reduced disruption of cardiac function and improved the indicators of ejection fraction (EF) and fractional shortening (FS). The enzyme-linked immunosorbent assay (ELISA) results suggested that OPA significantly reduced the release of myocardial infarction-related factors, such as the creatine kinase (CK-MB), cardiac troponin I (cTnI) and cardiac troponin T (cTnT). Additionally, hematoxylin-eosin (H&E) staining demonstrated that OPA markedly inhibited the myocardial apoptosis and necrosis caused by MI/R. Consistently, the results obtained from the cell counting kit-8 (CCK-8) and flow cytometry assays revealed that OPA obviously reversed the H/R-induced decrease in cell activity and increase in apoptosis of H9c2 cells. Furthermore, western blot assays indicated that OPA inhibited apoptosis by activating the Sirt1 (silent information regulator factor 2 related enzyme 1)/Foxo1(forkhead transcription factor FKHR) signaling pathway in myocardial tissues and H9c2 cells. Collectively, these novel findings are the first to provide strong evidence that OPA attenuates MI/R injury by activating the Sirt1 (silent information regulator factor 2 related enzyme 1)/Foxo1(forkhead transcription factor FKHR) signaling-mediated anti-apoptotic pathway.

Analysis of Chemical Components in the Roots of Eight Intersubgeneric Hybrids of Paeonia

“…Oxypaeoniflorin can reduce myocardial ischemia/reperfusion, thereby reducing myocardial cell apoptosis and necrosis [28] . Our results show that the content of oxypaeoniflorin in Y2 (10.10 mg/g) and Y6 (10.04 mg/g) was significantly higher than in other samples (<6.39 mg/g) ( Figure 3 B ).…”

Knockdown of lncRNA TTTY15 alleviates myocardial ischemia–reperfusion injury through the miR‐374a‐5p/FOXO1 axis

“…As an autophagy mediator, FOXO1 facilitates myocardial, renal, and cerebral I/R injury. [29][30][31] Additionally, knockdown of FOXO1 was shown to aggravate cardiomyocyte apoptosis by inhibiting autophagy. 32 F I G U R E 7 TTTY15 is a therapeutic target for I/R injury.…”

Oxypaeoniflorin Prevents Acute Lung Injury Induced by Lipopolysaccharide through the PTEN/AKT Pathway in a Sirt1‐Dependent Manner

“…Sirt1 global knockout mice with C57BL/6 background, weighing 23–25 g, were provided by the Model Animal Research Center of Nanjing University. As described [ 12 ], Oxy diluted in sterile saline containing DMSO was administered intragastrically at the concentration of 40 mg/kg/day for 30 consecutive days before LPS installation. The sepsis-induced ALI model was constructed by installing LPS intratracheally (5 mg/kg) for 12 hours as reported [ 14 ].…”

“…is a traditional Chinese herbal medicine belonging to the Ranunculaceae family, which possesses the ability to reduce pain, relieve abdominal cramps, and improve blood circulation [ 9 , 10 ]. Oxypaeoniflorin (Oxy) and paeoniflorin are two major active components in Paeonia lactiflora , both of which could exert anti-inflammatory and antiapoptotic effects [ 11 , 12 ]. In addition, as a monoterpene glycoside compound, Oxy could also inhibit advanced glycation end product-induced oxidative damage in mesangial cells [ 13 ].…”

“…In addition, as a monoterpene glycoside compound, Oxy could also inhibit advanced glycation end product-induced oxidative damage in mesangial cells [ 13 ]. One recent study also reported that Oxy improved myocardial ischemia/reperfusion (I/R) injury via activating the Sirt1/forkhead transcription factor FKHR (Foxo1) signaling pathway [ 12 ]. However, previous studies paid little attention to the beneficial effects in Oxy on ALI.…”