The protective effect of polyphyllin I on myocardial ischemia/ reperfusion injury in rats

Abstract

Background: Myocardial ischemia/reperfusion (I/R) injury has become a global public health concern.An increasing amount of evidence has shown that polyphyllin I (PPI) has anti-apoptotic and antioxidant functions. This study was performed to evaluate the cardioprotective effects of PPI in a rat model of myocardial I/R injury and the underlying mechanism. Methods:We exposed induced a rat model of I/R injury by exposing rat hearts to left anterior descending coronary artery ligation for 30 min, followed by 24 h of reperfusion. Cardiac function was analyzed by echocardiography and HE staining. Myocardial apoptosis, inflammation, and oxidative stress were detected to analyze the PPI's role in I/R injury. Results:The results showed that pretreatment with PPI improved impaired histological morphology, as shown by histopathological examination. Echocardiography analysis showed that PPI increased the levels of HR, left ventricular ejection fraction (LVEF), and left ventricular wall thickness (LVWT), accompanied by decreased left ventricular end-systolic volume (LVESV). Also, PPI decreased the expression of CK-MB, Mb, cTnI, and LDH. Specifically, PPI also changed the expression of apoptotic makers (Caspase-3, Bax, and Bcl-2), inflammatory cytokines (TNF-α, IL-6, iNOS, and IL-10) and oxidative stress markers (SOD, GSH, ROS, and MDA). Notably, western blot (WB) showed that PPI treatment inhibited the phosphorylation activity of NF-κB p65. Conclusions:The findings showed that PPI exerted a favorable protective effect on I/R injury by inhibiting the inflammatory response and oxidative stress. It offered new drug candidates for the treatment of myocardial I/R injury.

Role of Oxidative Stress in Reperfusion following Myocardial Ischemia and Its Treatments

“…It is thought that ROS upregulate IL-1 β through the NLRP3 inflammasome activation and caspase-1 expression [ 121 ]. IL-6 works as a downstream target of IL-1 β [ 159 ]. It was demonstrated that thioredoxin-interacting protein-mediated NLRP3 inflammasome activation in cardiac microvascular endothelial cells was a novel mechanism of MI/RI [ 160 ].…”

Downregulation of p300/CBP‐associated factor inhibits cardiomyocyte apoptosis via suppression of NF‐κB pathway in ischaemia/reperfusion injury rats

“…NF‐κB was a recognized transcription factor in modulation of inflammation, oxidative stress and cell apoptosis in the context of MIRI 17‐19 . The expression level of phospho‐NF‐κB p65 was significantly upregulated after H/R compared with the control cells.…”

“…Middle or high concentrations of ROS could induce inflammatory response and even apoptosis in cardiomyocytes through oxidative stress. 17,22 SOD is the main enzyme that eliminates ROS in cells. It can restore the dynamic balance of oxidation and anti-oxidation, and prevent ROS from causing damage to cells.…”

“…MDA is the end product of lipid peroxidation, which causes biological macromolecules to polymerize with each other, and is cytotoxic. Middle or high concentrations of ROS could induce inflammatory response and even apoptosis in cardiomyocytes through oxidative stress 17,22 . SOD is the main enzyme that eliminates ROS in cells.…”

“…NF-κB was a recognized transcription factor in modulation of inflammation, oxidative stress and cell apoptosis in the context of MIRI. [17][18][19] The expression level of phospho-NF-κB p65 was significantly upregulated after H/R compared with the control cells. While H9c2 cells were transfected with Ad-shRNA-PCAF, the protein level of The results of Co-IP showed that there was a direct interaction between PCAF and NF-κB p65, and after H/R induction, the interaction between PCAF and NF-κB became stronger (Figure 6C).…”