Rosa rugosa flavonoids alleviate myocardial ischemia reperfusion injury in mice by suppressing JNK and p38 MAPK

Abstract

Objective: Although Rosa rugosa has been applied for preventing coronary artery disease, the pharmacological mechanism is little explored. In this study, the effects and mechanisms of Rosa rugosa flavonoids (RRF) on myocardial ischemia reperfusion injury (MIRI) were investigated. Methods:Mice were pretreated by intragastric administration of 600 mg/kg RRF for 7 days. Then MIRI was induced by 45 minutes coronary artery ligation and 3 hours reperfusion. Myocardial infarct size (MIS) and histopathology, activities of myocardial enzymes, and effects of RRF on inflammation and apoptosis were evaluated.Results: Pretreating the mice with RRF significantly reduced MIS and inhibited activity of plasma myocardial enzymes. Activity of the enzymes associated with anti-oxidation, SOD, and TEAC, and mRNA expression of NOX2 were significantly elevated. RRF pretreatment significantly decreased the translocation of p65 from the cytoplasm into the nucleus and reduced the expression of the pro-inflammatory cytokines, IL-6 and IL-1β. RRF pretreatment also significantly prevented the expression of caspase-3 and Bax, and increased the expression of Bcl-2. And RRF inhibited the phosphorylation of JNK and p38 MAPK.Conclusions: RRF significantly inhibited MIRI through anti-oxidative, anti-inflammatory, and anti-apoptosis effects, and mechanisms were associated with its inhibition on phosphorylation of JNK and p38 MAPK. K E Y W O R D Santi-apoptosis, anti-inflammation, anti-oxidation, mitogen-activated protein kinase, myocardial ischemia reperfusion injury, rosa rugosa flavonoids

DUSP1 alleviates cardiac ischemia/reperfusion injury by suppressing the Mff-required mitochondrial fission and Bnip3-related mitophagy via the JNK pathways

“…ERK is activated by various growth factors, controls cell growth and promotes cellular survival in IR injury [42] . In contrast, p38 and JNK are activated by stress conditions, leading to the cellular apoptosis via multiple mechanisms [43] . Several studies have argued that the intensity and balance of MAPK activities are important determinants of the cell fate.…”

The Protective Effect of Shuxin Shengmai Dan on Myocardial Ischemia-Reperfusion Injury in Rats

“…Zhaoqi H. et al used c57BL6/J mice to establish a MIRI model to study the protective effect of microRNA-374a targeting the MAPK6 pathway [18]. Xuehui Z. use ICR mice to establish a MIRI model to study inhibition of the JNK and p38 MAPK by Rosa rugosa avonoids to reduce myocardial ischemia-reperfusion injury [19]. Yang D. et al developed an SD rat MIRI model by ligating LAD for 1 h and subsequent reperfusion for 24 h [20].…”

A novel small molecule compound VCP979 improves ventricular remodeling in murine models of myocardial ischemia/reperfusion injury

“…Preclinical evidence has shown that myocardial ischemia is a potent stimulant of p38 activation, which might increase the production of inflammatory cytokines and accelerate the rate of infarction/death (9). A previous study has demonstrated that the p38-MAPK signaling pathway inhibitor SB203580 significantly repressed MI/R injury through its anti-inflammatory, anti-oxidative and anti-apoptosis effects (47). In the present experiments, the small-molecule compound VCP979 inhibited the MI/R injury-triggered activation of the p38-MAPK signaling pathway in murine models.…”