Ayesheh Enayati1, Narguess Yassa2, Zohreh Mazaheri3, Maryam Rajaei4, Mona Pourabouk4, Sajjad Ghorghanlu4, Salar Basiri4, Vahid Khori5. 1. Department of Pharmacognosy, Faculty of Pharmacy, Medicinal Plants Research Center, Tehran University of Medical Sciences, Tehran, Iran; Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran. Electronic address: a-enayati@razi.tums.ac.ir. 2. Department of Pharmacognosy, Faculty of Pharmacy, Medicinal Plants Research Center, Tehran University of Medical Sciences, Tehran, Iran. 3. Basic Medical Science Research Center, Histogenotech Company, Tehran, Iran. 4. Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran. 5. Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran. Electronic address: vahid.khori@yahoo.com.
Abstract
BACKGROUND: Previous studies have shown that proanthocyanidins have cardioprotective effects which are mediated via the release of nitric oxide (NO) ultimately resulting in increasing the antioxidant activity. We have investigated to show whether 1) the total extract and ethyl acetate fraction (Et) of Potentilla reptans root have an ischemic preconditioning (IPC) effect, 2) P. reptans has antioxidant and cardioprotective effects mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and scavenging of reactive oxygen species (ROS), 3) NO, caspase-3 and Bcl-2/Bax are involved in the IPC effect of P. reptans. METHODS: Male Wistar rats were divided into 10 groups. The isolated hearts were subjected to 30 min of ischemia and 100 min of reperfusion. The P. reptans was applied before the main ischemia. The infarct size was estimated by triphenyl-tetrazolium chloride staining. The hemodynamic parameters and ventricular arrhythmias were calculated during the reperfusion. Antioxidant markers and immunohistochemistry assays were determined at the end of the protocol. RESULTS: The Et significantly decreased the infarct size, arrhythmia scores, ventricular fibrillation incidence, and enhanced the hemodynamic parameters in a concentration-dependent manner against the ischemia/reperfusion group. SOD and CAT activity were increased and MDA level was decreased in response to the Et. Meanwhile, Et attenuated the suppression of Nrf2 expression and reduced the apoptotic indexes. The cardioprotective effect of P. reptans was abrogated by L-NAME. CONCLUSIONS: P. reptans demonstrated that the cardioprotective preconditioning effects via NO release, Nrf2 pathway, and antioxidant activity lead to a decrease in the apoptotic index.
BACKGROUND: Previous studies have shown that proanthocyanidins have cardioprotective effects which are mediated via the release of nitric oxide (NO) ultimately resulting in increasing the antioxidant activity. We have investigated to show whether 1) the total extract and ethyl acetate fraction (Et) of Potentilla reptans root have an ischemic preconditioning (IPC) effect, 2) P. reptans has antioxidant and cardioprotective effects mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and scavenging of reactive oxygen species (ROS), 3) NO, caspase-3 and Bcl-2/Bax are involved in the IPC effect of P. reptans. METHODS: Male Wistar rats were divided into 10 groups. The isolated hearts were subjected to 30 min of ischemia and 100 min of reperfusion. The P. reptans was applied before the main ischemia. The infarct size was estimated by triphenyl-tetrazolium chloride staining. The hemodynamic parameters and ventricular arrhythmias were calculated during the reperfusion. Antioxidant markers and immunohistochemistry assays were determined at the end of the protocol. RESULTS: The Et significantly decreased the infarct size, arrhythmia scores, ventricular fibrillation incidence, and enhanced the hemodynamic parameters in a concentration-dependent manner against the ischemia/reperfusion group. SOD and CAT activity were increased and MDA level was decreased in response to the Et. Meanwhile, Et attenuated the suppression of Nrf2 expression and reduced the apoptotic indexes. The cardioprotective effect of P. reptans was abrogated by L-NAME. CONCLUSIONS:P. reptans demonstrated that the cardioprotective preconditioning effects via NO release, Nrf2 pathway, and antioxidant activity lead to a decrease in the apoptotic index.