RESUMO
ABSTRACT: Panax notoginseng saponins (PNS) are commonly used in the treatment of cardiovascular diseases. Whether PNS can protect myocardial ischemia-reperfusion injury by regulating the forkhead box O3a hypoxia-inducible factor-1 alpha (FOXO3a/HIF-1α) cell signaling pathway remains unclear. The purpose of this study was to investigate the protective effect of PNS on H9c2 cardiomyocytes through the FOXO3a/HIF-1α cell signaling pathway. Hypoxia and reoxygenation of H9C2 cells were used to mimic MIRI in vitro, and the cells were treated with PNS, 2-methoxyestradiol (2ME2), and LY294002." Cell proliferation, lactate dehydrogenase, and malonaldehyde were used to evaluate the degree of cell injury. The level of reactive oxygen species was detected with a fluorescence microscope. The apoptosis rate was detected by flow cytometry. The expression of autophagy-related proteins and apoptosis-related proteins was detected by western blot assay. PNS could reduce H9c2 hypoxia-reoxygenation injury by promoting autophagy and inhibiting apoptosis through the HIF-1α/FOXO3a cell signaling pathway. Furthermore, the protective effects of PNS were abolished by HIF-1α inhibitor 2ME2 and PI3K/Akt inhibitor LY294002. PNS could reduce H9c2 hypoxia-reoxygenation injury by promoting autophagy and inhibiting apoptosis through the HIF-1α/FOXO3a cell signaling pathway.
Assuntos
Fármacos Cardiovasculares/farmacologia , Proteína Forkhead Box O3/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Panax notoginseng , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Fármacos Cardiovasculares/isolamento & purificação , Linhagem Celular , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Panax notoginseng/química , Fosfatidilinositol 3-Quinase/metabolismo , Extratos Vegetais/isolamento & purificação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , Saponinas/isolamento & purificação , Transdução de SinaisRESUMO
BACKGROUND AND OBJECTIVE: Panax Notoginseng Saponins (PNS) is a formula of Chinese medicine commonly used for treating ischemia myocardial in China. However, its mechanism of action is yet unclear. This study investigated the effect and the mechanism of PNS on myocardial ischemia-reperfusion injury (MIRI) through the hypoxia-inducible factor 1α (HIF-1α)/bcl-2/adenovirus E1B19kDa-interacting protein3 (BNIP3) pathway of autophagy. METHODS: We constructed a rat model of myocardial injury and compared among 4 groups (n = 10, each): the sham-operated group (Sham), the ischemia-reperfusion group (IR), the PNS low-dose group, and the PNS high-dose group were pretreated with PNS (30 and 60 mg/kg, respectively). Serum creatine kinase, malonaldehyde (MDA), lactate dehydrogenase, myocardial tissue superoxide dismutase, and reactive oxygen species were detected in rats with myocardial ischemia-reperfusion after the intervention of PNS. The rat myocardial tissue was examined using hematoxylin and eosin (H&E) staining, and the mitochondria of myocardial cells were observed using transmission electron microscopy. The expressions of microtubule-associated protein light chain 3 (LC3), HIF-1α, BNIP3, Beclin-1, and autophagy-related gene-5 (Atg5) in rat myocardial tissue were detected using Western blotting. RESULTS: The results showed that PNS was significantly protected against MIRI, as evidenced by the decreasing in the concentration of serum CK, MDA, lactate dehydrogenase, and myocardial tissue superoxide dismutase, reactive oxygen species, the attenuation of myocardial tissue histopathological changes and the mitochondrial damages of myocardial cells, and the increase of mitochondria autophagosome in myocardial cells. In addition, PNS significantly increased the expression of LC3 and the ratio of LC3II/LC3I in rat myocardial tissue. Moreover, PNS significantly increased the expression of HIF-1α, BNIP3, Atg5, and Beclin-1 in rat myocardial tissue. CONCLUSIONS: The protective effect of PNS on MIRI was mainly due to its ability to enhance the mitochondrial autophagy of myocardial tissue through the HIF-1α/BNIP3 pathway.
Assuntos
Autofagia/efeitos dos fármacos , Fármacos Cardiovasculares/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Panax , Saponinas/farmacologia , Animais , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína Beclina-1/metabolismo , Fármacos Cardiovasculares/isolamento & purificação , Modelos Animais de Doenças , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/ultraestrutura , Panax/química , Ratos Sprague-Dawley , Saponinas/isolamento & purificação , Transdução de SinaisRESUMO
The Cd(II) ion in the title complex, [Cd(SCN)(2)[SC(NH(2))(2)](2)](infinity), is situated at a centre of symmetry, and is bound to two N atoms belonging to thiocyanate groups and to four S atoms of bridging thiourea ligands. The structure consists of infinite chains of slightly distorted edge-shared Cd-centred octahedra. The bridging S atoms of two thiourea ligands comprise the common edge. Some thermal properties are described.
RESUMO
The title complex, [[CdHg(SCN)(4)(C(4)H(9)NO)(2)](2)](n), contains two crystallographically independent Cd(II) centres and two Hg(II) centres. Each Cd(II) atom is bound to four N atoms belonging to SCN groups and to two O atoms from N,N-dimethylacetamide (DMA) ligands in an octahedral geometry. Each Hg(II) centre is tetrahedrally coordinated by four SCN S atoms.