Saponins from Rhizoma Panacis Majoris attenuate myocardial ischemia/reperfusion injury via the activation of the Sirt1/Foxo1/Pgc-1α and Nrf2/antioxidant defense pathways in rats

Pharmacognosy Magazine,2018,14,56,297-307.DOI:10.4103/pm.pm_467_17Published:August 2018Type:Original ArticleAuthors:Hai-Bo He, Xiao-Mei Li, Dao-Jun Li, Yong-Hong Ding, Yong-Feng Zhang, Hai-Yan Xu, Min-Lu Feng, Chang-Qing Xiang, Ji-Gang Zhou, Ji-Hong Zhang, Hong-Jun Liu, and Mao-Hua Chen Author(s) affiliations:Hai-Bo He1, Xiao-Mei Li2, Dao-Jun Li3, Yong-Hong Ding2, Yong-Feng Zhang2, Hai-Yan Xu2, Min-Lu Feng2, Chang-Qing Xiang4, Ji-Gang Zhou5, Ji-Hong Zhang5, Hong-Jun Liu5, Mao-Hua Chen5 1 Department of Pharmacology, Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University; Institute of Cardiovascular Diseases, Key Laboratory of Ischemic Cardiovascular and Cerebrovascular Disease Translational Medicine, Three Gorges University, Yichang, Hubei, China 2 Department of Pharmacology, Hubei Key Laboratory of Natural Products Research and Development, College of Biological and Pharmaceutical Sciences, China Three Gorges University, Yichang, Hubei, China 3 Institute of Cancer Research, The First Clinical Medical College and Yichang Central Hospital, China Three Gorges University, Yichang, Hubei, China 4 Institute of Integration of Traditional Chinese and Western Medicine, The Second People's Hospital, China Three Gorges University, Yichang, Hubei, China 5 Institute of Cardiovascular Disease, Traditional Chinese Medicine Hospital of China Three Gorges University & Yichang Hospital of Traditional Chinese Medicine, Yichang, Hubei, China Abstract:Background: Saponins from Rhizoma Panacis Majoris (SRPM) are confirmed to have cardioprotective effect against myocardial ischemia injury by reducing oxidative stress, while its underlying mechanism has not been elucidated until recently. Objective: The objective of this study was to investigate the SRPM's cardioprotection and elucidate its underlying mechanisms. Materials and Methods: Adult male rats were received SRPM treatment in the presence or the absence of the silent information regulator 1 (Sirt1) inhibitor Ex-527 or nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ATRA for 14 days and subjected to myocardial ischemia for 0.5 h and then 2 h reperfusion. Cardiac function, infarct size, antioxidant enzyme activities, ROS level and the related mRNA and protein expressions of antiapoptosis protein Bcl-2, proapoptosis protein Bax, caspase-3, caspase-9, Sirt1 and Nrf2-relatived signaling pathways were assessed. Results: SRPM was confirmed to have cardioprotective effects by ameliorating cardiac function, decreasing infarct size, reducing serum creatine kinase (CK), creatine kinase isoenzyme, lactate dehydrogenase and ROS releases and malondialdehyde level, raising total antioxidant capacity, superoxide dismutase, glutathione peroxidase, catalase activities, upregulating myocardial Sirt1, Nrf2, Bcl-2 protein and manganese superoxide dismutase, heme oxygenase-1, NAD(P)H-quinone oxidoreductase 1 and γ-glutamylcysteine synthetase mRNA expressions and downregulating acetylated forkhead box O 1, acetylated peroxisome proliferator-activated receptor γ coactivator 1α, Bax, cleaved caspase-3 and cleaved caspase-9 protein expressions; histopathological observations provided supportive evidence for the aforementioned results. Interestedly, its protective effects were significantly blocked for its combination with Ex-527 or ATRA. Conclusion: The studies demonstrated that SRPM exerted beneficially protective effects on myocardial ischemia/reperfusion injury. It was possibly related to reducing oxidative stress damage by activations of Sirt1 and Nrf2-related antioxidant signaling pathways. Keywords:Cardioprotection, Ischemia reperfusion, Nrf2 signaling pathway, oxidative stress, Saponins from Rhizoma Panacis Majoris, Sirt1 signaling pathwayView:PDF (2.74 MB)