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Danhong injection protects cardiomyocytes against hypoxia/reoxygenation- and H2O2-induced injury by inhibiting mitochondrial permeability transition pore opening

Authors Duan, Zhen-Zhen; Li, Yu-Hong; Li, Yan-Yan; Fan, Guan-Wei; Chang, Yan-Xu; Yu, Bin; Gao, Xiu-Mei

Journal JOURNAL OF ETHNOPHARMACOLOGY , DEC 4 2015,:175

DOI 10.1016/j.jep.2015.08.033 PubMed 26320687

Abstract Ethnopharmacological relevance: Danhong injection (DHI), a Chinese medical product extracted from Radix et Rhizoma Salviae Miltiorrhizae (Salvia miltiorrhiza Bge., Labiatae, Danshen in Chinese) and Flos Carthami (Carthamus tinctorius L., Compositae, Honghua in Chinese), has been widely used for the treatment of ischemic heart disease, and clinical and experimental studies have demonstrated the protective effects against myocardial ischemia/reperfusion injury. Nevertheless, the underlying cellular mechanisms responsible for this protective effect are poorly understood.Aim of the study: The present study aimed to examine the mechanism of DHI in regulating hypoxia/reoxygenation- and H2O2-induced cardiomyocytes injury.Materials and methods: Neonatal rat cardiomyocytes were subjected to hypoxia (9 h)-reoxygenation (2 h) or H2O2 (100 mu M) in the presence or absence of DHI (2.5, 5, 10 mu g/mL). Intracellular reactive oxygen species (ROS), cytosolic and mitochondrial Ca2+ concentrations, mitochondrial membrane potential (Delta psi m) and mitochondrial permeability transition pore (mPTP) opening were monitored using CMH(2)DCFDA, Fluo-4 and rhod-2, JC-1 and calcein, respectively. Cell survival was evaluated using the 2-(4,5-dimethylthiazol-2-y1)-2,5 -diphenyltetrazolium bromide (MIT) assay and apoptosis was detected by Annexin V/propidium iodide (PI) staining.Results: DHI improved cell survival following H/R and H2O2 injury and reduced H/R-induced cytochrome c release and apoptosis when compared with non-DHI treated cells. In addition, DHI attenuated H/R-induced ROS generation, H2O2-induced cytosolic and mitochondrial Ca2+ overload, and cellular ROS generation when compared with H/R- and H2O2-only groups. Moreover, DHI significantly inhibited both mPTP opening and Delta psi m depolarization.Conclusion: These data demonstrate that the protective mechanism of DHI against H/R- and H2O2-induced injury is mediated by the inhibition of mPTP opening via mitigating Ca2+ overload and ROS generation. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Species covered 红花 Carthamus tinctorius 丹参 Salvia miltiorrhiza