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Molecular mechanism of luteolin regulating lipoxygenase pathway against oxygen-glucose deprivation/reperfusion injury in H9c2 cardiomyocytes based on molecular docking / 中国中药杂志
China Journal of Chinese Materia Medica ; (24): 5665-5673, 2021.
Article in Chinese | WPRIM | ID: wpr-921751
ABSTRACT
The aim of this study was to investigate the mechanism of luteolin regulating lipoxygenase pathway against oxygen-glucose deprivation/reperfusion(OGD/R) injury in H9 c2 cardiomyocytes. First, Discovery Studio 2019 was used for the molecular docking of luteolin with three key enzymes including lipoxygenase 5(ALOX5), lipoxygenase 12(ALOX12), and lipoxygenase 15(ALOX15) in lipoxygenase pathway. The docking results showed that luteolin had high docking score and similar functional groups with the original ligand. From this, H9 c2 cardiomyocytes were cultured in vitro, and then the injury model of H9 c2 cardiomyocytes was induced by deprivation of oxygen-glucose for 8 h, and rehabilitation of oxygen-glucose for 12 h. Cell viability was detected by tetrazolium(MTT) colorimetry. H9 c2 cardiomyocytes were observed with a fluorescence inverted microscope, and colorimetry was used to detect the level of lactate dehydrogenase(LDH) in cell supernatant. The results showed that luteolin could significantly protect the morphology of H9 c2 cells, significantly improve the survival rate of H9 c2 cardiomyocytes in OGD/R injury model, reduce the level of LDH in cell supernatant, inhibit cytotoxicity, and maintain the integrity of cell membrane. The inflammatory cytokines interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected by enzyme-linked immunosorbent assay. Compared with the model group, luteolin can significantly reduce the release of IL-6 and TNF-α. Western blot was employed to detect the protein levels of ALOX5, ALOX12, and ALOX15 in lipoxygenase pathway. After luteolin intervention, the protein levels of ALOX5, ALOX12, and ALOX15 were significantly down-regulated compared with those in model group. These results indicate that luteolin can inhibit the release of IL-6 and TNF-α by restraining the activation of lipoxygenase pathway, thereby playing a protective role in the cardiomyocyte injury model induced by OGD/R.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Oxygen / Reperfusion Injury / Signal Transduction / Apoptosis / Myocytes, Cardiac / Luteolin / Lipoxygenases / Molecular Docking Simulation / Glucose Type of study: Prognostic study Limits: Humans Language: Chinese Journal: China Journal of Chinese Materia Medica Year: 2021 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Oxygen / Reperfusion Injury / Signal Transduction / Apoptosis / Myocytes, Cardiac / Luteolin / Lipoxygenases / Molecular Docking Simulation / Glucose Type of study: Prognostic study Limits: Humans Language: Chinese Journal: China Journal of Chinese Materia Medica Year: 2021 Type: Article