Exploring the protective effects of schizandrol A in acute myocardial ischemia mice by comprehensive metabolomics profiling integrated with molecular mechanism studies
| العنوان: | Exploring the protective effects of schizandrol A in acute myocardial ischemia mice by comprehensive metabolomics profiling integrated with molecular mechanism studies |
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| المؤلفون: | Boyang Yu, Guangying Yuan, Fang Li, Zeliang Liu, Junping Kou, Hao Wang, Qiong Lai |
| المصدر: | Acta Pharmacologica Sinica |
| بيانات النشر: | Springer Science and Business Media LLC, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Cardiotonic Agents, Arginine, Myocardial Ischemia, Apoptosis, schizandrol A, Endogeny, Pharmacology, therapeutic targets, Lignans, Article, Cell Line, Serine, Cyclooctanes, acute myocardial ischemia mice, 03 medical and health sciences, 0302 clinical medicine, Animals, Metabolomics, metabolic pathways, Myocytes, Cardiac, Polycyclic Compounds, metabonomics, Pharmacology (medical), Protein Interaction Maps, Methionine synthase, cardioprotective effect, Protein kinase B, PI3K/AKT/mTOR pathway, Mice, Inbred ICR, biology, Chemistry, Myocardium, General Medicine, Enzymes, Rats, Guanidinoacetate N-methyltransferase, 030104 developmental biology, OGD-treated H9c2 cardiomycytes, 030220 oncology & carcinogenesis, Pyrimidine metabolism, biology.protein, Signal Transduction |
| الوصف: | Schizandrol A (SA) is an bioactive component isolated from the Schisandra chinensis (Turcz.) Baill., which has been used as a remedy to prevent oxidative injury. However, whether the cardioprotective effect of SA is associated with regulating endogenous metabolites remains unclear, thus we performed comprehensive metabolomics profiling in acute myocardial ischemia (AMI) mice following SA treatment. AMI was induced in ICR mice by coronary artery ligation, then SA (6 mg·kg −1 ·d −1 , ip) was administered. SA treatment significantly decreased the infarct size, preserved the cardiac function, and improved the biochemical indicators and cardiac pathological alterations. Moreover, SA (10, 100 M) significantly decreased the apoptotic index in OGD-treated H8c2 cardiomycytes in vitro. By using HPLC-Q-TOF/MS, we conducted metabonomics analysis to screen the significantly changed endogenous metabolites and construct the network in both serum and urine. The results revealed that SA regulated the pathways of glycine, serine and threonine metabolism, lysine biosynthesis, pyrimidine metabolism, arginine and proline metabolism, cysteine and methionine metabolism, valine, leucine and isoleucine biosynthesis under the pathological conditions of AMI. Furthermore, we selected the regulatory enzymes related to heart disease, including ecto-5’-nucleotidase (NT5E), guanidinoacetate Nmethyltransferase (GAMT), platelet-derived endothelial cell growth factor (PD-ECGF) and methionine synthase (MTR), for validation. In addition, SA was found to facilitate PI3K/Akt activation and inhibit the expression of NOX2 in AMI mice and OGD-treated H9c2 cells. In conclusion, we have elucidated SA-regulated endogenous metabolic pathways and constructed a regulatory metabolic network map. Furthermore, we have validated the new potential therapeutic targets and underlying molecular mechanisms of SA against AMI, which might provide a reference for its future application in cardiovascular diseases. |
| تدمد: | 1745-7254 1671-4083 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5ac865e1c0597e2b6a47f622c1cff41dTest https://doi.org/10.1038/s41401-020-0377-7Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....5ac865e1c0597e2b6a47f622c1cff41d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17457254 16714083 |
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