Potentilla reptans L. postconditioning protects reperfusion injury via the RISK/SAFE pathways in an isolated rat heart

Abstract Background 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 present study, we investigated the post-conditioning cardio-protective effects of...

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Main Authors: Ayesheh Enayati, Aref Salehi, Mostafa Alilou, Hermann Stuppner, Mirali Polshekan, Maryam Rajaei, Mona Pourabouk, Ali Jabbari, Zohreh Mazaheri, Narguess Yassa, Hamid Reza Moheimani, Vahid Khori
Format: Article
Language:English
Published: BMC 2021-11-01
Series:BMC Complementary Medicine and Therapies
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Online Access:https://doi.org/10.1186/s12906-021-03456-2
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author Ayesheh Enayati
Aref Salehi
Mostafa Alilou
Hermann Stuppner
Mirali Polshekan
Maryam Rajaei
Mona Pourabouk
Ali Jabbari
Zohreh Mazaheri
Narguess Yassa
Hamid Reza Moheimani
Vahid Khori
author_facet Ayesheh Enayati
Aref Salehi
Mostafa Alilou
Hermann Stuppner
Mirali Polshekan
Maryam Rajaei
Mona Pourabouk
Ali Jabbari
Zohreh Mazaheri
Narguess Yassa
Hamid Reza Moheimani
Vahid Khori
author_sort Ayesheh Enayati
collection DOAJ
description Abstract Background 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 present study, we investigated the post-conditioning cardio-protective effects of Potentilla reptans and its active substances. Methods The 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. Results Et 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. Conclusion P. 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.
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spelling doaj.art-cde7c981b51e41d39ddae2dd084682f72022-12-21T21:23:50ZengBMCBMC Complementary Medicine and Therapies2662-76712021-11-0121111510.1186/s12906-021-03456-2Potentilla reptans L. postconditioning protects reperfusion injury via the RISK/SAFE pathways in an isolated rat heartAyesheh Enayati0Aref Salehi1Mostafa Alilou2Hermann Stuppner3Mirali Polshekan4Maryam Rajaei5Mona Pourabouk6Ali Jabbari7Zohreh Mazaheri8Narguess Yassa9Hamid Reza Moheimani10Vahid Khori11Ischemic Disorders Research Center, Golestan University of Medical SciencesIschemic Disorders Research Center, Golestan University of Medical SciencesInstitute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck, University of InnsbruckInstitute of Pharmacy/Pharmacognosy, Center for Molecular Biosciences Innsbruck, University of InnsbruckIschemic Disorders Research Center, Golestan University of Medical SciencesIschemic Disorders Research Center, Golestan University of Medical SciencesIschemic Disorders Research Center, Golestan University of Medical SciencesIschemic Disorders Research Center, Golestan University of Medical SciencesIschemic Disorders Research Center, Golestan University of Medical SciencesDepartment of Pharmacognosy, Faculty of Pharmacy and Medicinal Plants Research Center, Tehran University of Medical SciencesIschemic Disorders Research Center, Golestan University of Medical SciencesIschemic Disorders Research Center, Golestan University of Medical SciencesAbstract Background 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 present study, we investigated the post-conditioning cardio-protective effects of Potentilla reptans and its active substances. Methods The 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. Results Et 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. Conclusion P. 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.https://doi.org/10.1186/s12906-021-03456-2Potentilla reptans rootPostconditioningAnti-apoptoticAntioxidantNOGSK-3β
spellingShingle Ayesheh Enayati
Aref Salehi
Mostafa Alilou
Hermann Stuppner
Mirali Polshekan
Maryam Rajaei
Mona Pourabouk
Ali Jabbari
Zohreh Mazaheri
Narguess Yassa
Hamid Reza Moheimani
Vahid Khori
Potentilla reptans L. postconditioning protects reperfusion injury via the RISK/SAFE pathways in an isolated rat heart
BMC Complementary Medicine and Therapies
Potentilla reptans root
Postconditioning
Anti-apoptotic
Antioxidant
NO
GSK-3β
title Potentilla reptans L. postconditioning protects reperfusion injury via the RISK/SAFE pathways in an isolated rat heart
title_full Potentilla reptans L. postconditioning protects reperfusion injury via the RISK/SAFE pathways in an isolated rat heart
title_fullStr Potentilla reptans L. postconditioning protects reperfusion injury via the RISK/SAFE pathways in an isolated rat heart
title_full_unstemmed Potentilla reptans L. postconditioning protects reperfusion injury via the RISK/SAFE pathways in an isolated rat heart
title_short Potentilla reptans L. postconditioning protects reperfusion injury via the RISK/SAFE pathways in an isolated rat heart
title_sort potentilla reptans l postconditioning protects reperfusion injury via the risk safe pathways in an isolated rat heart
topic Potentilla reptans root
Postconditioning
Anti-apoptotic
Antioxidant
NO
GSK-3β
url https://doi.org/10.1186/s12906-021-03456-2
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