Abstract
BackgroundOur previous study indicated that Potentilla reptans root has a preconditioning effect by its antioxidant and anti-apoptotic effects in an isolated rat heart ischemia/reperfusion (IR) model. In the present study, we investigated the post-conditioning cardio-protective effects of Potentilla reptans and its active substances.MethodsThe ethyl acetate fraction of P. reptans root (Et) was subjected to an IR model under 30 min of ischemia and 100 min of reperfusion. To investigate the postconditioning effect, Et was perfused for 15 min at the early phase of reperfusion. RISK/SAFE pathway inhibitors, 5HD and L-NAME, were applied individually 10 min before the ischemia, either alone or in combination with Et during the early reperfusion phase. The hemodynamic factors and ventricular arrhythmia were calculated during the reperfusion. Oxidative stress, apoptosis markers, GSK-3β and SGK1 proteins were assessed at the end of experiments.ResultsEt postconditioning (Etpost) significantly reduced the infarct size, arrhythmia score, ventricular fibrillation incidence, and enhanced the hemodynamic parameters by decreasing the MDA level and increasing expression of Nrf2, SOD and CAT activities. Meanwhile, Etpost increased the BCl-2/BAX ratio and decreased Caspase-3 expression. The cardioprotective effect of Etpost was abrogated by L-NAME, Wortmannin (a PI3K/Akt inhibitor), and AG490 (a JAK/STAT3 inhibitor). Finally, Etpost reduced the expression of GSK-3β and SGK1 proteins pertaining to the IR group.ConclusionP. reptans reveals the post-conditioning effects via the Nrf2 pathway, NO release, and the RISK/SAFE pathway. Also, Etpost decreased apoptotic indexes by inhibiting GSK-3β and SGK1 expressions. Hence, our data suggest that Etpost can be a suitable natural candidate to protect cardiomyocytes during reperfusion injury.
Highlights
Our previous study indicated that Potentilla reptans root has a preconditioning effect by its antioxidant and anti-apoptotic effects in an isolated rat heart ischemia/reperfusion (IR) model
In the current study, we aimed to evaluate the cardioprotective effect of ethyl acetate fraction of Potentilla reptans root based on its underlying mechanisms in NO, Nrf2, mitoKATP, RISK/SAFE signaling pathways, Glycogen synthase kinase 3β (GSK-3β), SGK1, and anti-apoptotic index pertaining to the recorded evidences of pharmacological in the rat heart IR injury
The results revealed that Wort, PD, AG, 5HD, and L-NAME abolished the cardioprotective role of Et postconditioning (Etpost) (9.79 ± 1.1) in the reduction of infarct size (IS), but the effect of 5HD was not significant (13.49 ± 2.6) (P < 0.05, Fig. 2)
Summary
Our previous study indicated that Potentilla reptans root has a preconditioning effect by its antioxidant and anti-apoptotic effects in an isolated rat heart ischemia/reperfusion (IR) model. Reactive oxygen species (ROS) play an essential role in ischemic postconditioning via the intervention of redox signaling using either ROS scavengers or ROS generators during the early myocardial reperfusion [1]. The previous studies showed that medicinal plants such as Potentilla species and their active ingredients including flavan-3-ols can suppress ROS and incite the release of NO through the down/upregulation of several signaling cascades involved during reperfusion injury [5,6,7]. It could be valuable, finding new natural pharmacological agents that protect cardiac against IR injury by modifying involved mechanisms
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