baohuoside-i and Myocardial-Infarction

Nuclear factor erythroid 2-related factor 2 (Nrf2)/silent mating type information regulation 2 homolog 3 (SIRT3) signaling pathway plays a pivotal role in regulating mitochondrial dynamics and oxidative stress, which are considered to be the principal pathogenesis of myocardial infarction (MI). Our previous study proved that pretreatment with icariside II (ICS II), a major active ingredient of Herbal Epimedii, exerts cardioprotective effect on MI, however, whether post-treatment with ICS II can alleviate MI and its underlying mechanism are still uncertain. Therefore, the present study was designed to investigate the therapeutic effect and the possible mechanism of ICS II on MI both in vivo and in vitro. The results revealed that post-treatment with ICS II markedly ameliorated myocardial injury in MI-induced mice and mitigated oxygen and glucose deprivation (OGD)-elicited cardiomyocyte injury. Further researches showed that ICS II promoted mitochondrial fusion, and suppressed mitochondrial fission and oxidative stress, which were achieved by facilitating the nuclear translocation of Nrf2 and activation of SIRT3. In summary, our findings indicate that ICS II mitigates MI-induced mitochondrial dynamics disorder and oxidative stress via activating the Nrf2/SIRT3 signaling pathway.

Topics: Animals; Apoptosis; Mice; Mitochondrial Dynamics; Myocardial Infarction; NF-E2-Related Factor 2; Oxidative Stress; Signal Transduction; Sirtuin 3

Icariside II (ICS II) has been reported to have protective effects against oxidative stress. However, whether ICS II protects cardiomyocytes from myocardial infarction (MI), and the associated underlying mechanisms, remain to be elucidated. Therefore, the current study investigated the effects of ICS II on hypoxia‑injured H9c2 cells, as well as the associated molecular mechanisms. A hypoxic injury model was established to emulate the effects of MI. The effects of ICS II on the proliferation of rat cardiomyocyte H9c2 cells were assessed with cell counting kit‑8 assays. The apoptotic status of the cells was assessed by flow cytometry, and the expression of apoptosis‑related proteins was analyzed by western blotting. A microRNA (miRNA/miR) microarray was used to quantify the differential expression of miRNAs after ICS II treatment, and the levels of miR‑7‑5p were further quantified by reverse transcription‑quantitative PCR. Whether ICS II affected hypoxia‑injured cells via miR‑7‑5p was subsequently examined, and the target of miR‑7‑5p was also investigated by bioinformatics analysis and luciferase reporter assays. The effects of ICS II on the PI3K/Akt pathway were then evaluated by western blot analysis. Hypoxia treatment decreased viability and the migration and invasion abilities of H9c2 cells, and also induced apoptosis. ICS II significantly increased viability and reduced hypoxia‑associated apoptosis. Moreover, ICS II treatment led to the upregulation of miR‑7‑5p, and the protective effects of ICS II were found to rely on miR‑7‑5p. Moreover, BTG anti‑proliferation factor (BTG2) was identified as a direct target of miR‑7‑5p, and overexpression of BTG2 inhibited the protective effects of miR‑7‑5p. Finally, ICS II treatment resulted in the activation of the PI3K/Akt signaling pathway, which is essential for the survival of H9c2 cells under hypoxic conditions. In summary, ICS II reduces hypoxic injury in H9c2 cells via the miR‑7‑5p/BTG2 axis and activation of the PI3K/Akt signaling pathway.

Topics: Animals; Apoptosis; Cell Survival; Cells, Cultured; Flavonoids; Hypoxia; Immediate-Early Proteins; MicroRNAs; Myocardial Infarction; Myocytes, Cardiac; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Signal Transduction; Tumor Suppressor Proteins; Up-Regulation