Establishment of fingerprint and mechanism of anti-myocardial ischemic effect of Syringa pinnatifolia

Biomed Chromatogr. 2022 Nov;36(11):e5475. doi: 10.1002/bmc.5475. Epub 2022 Sep 7.

Abstract

This study established the fingerprint of Syringa pinnatifolia Hemsl. (SP), analyzed the SP ingredients absorbed into the rats blood, and evaluated its anti-myocardial ischemic effect to provide a scientific basis for the follow-up development and research of SP and lay a foundation for its clinical application using ultra-performance liquid chromatography-Q Exactive-mass spectrometry and GC-MS. Myocardial infarction was induced in rat by ligating the left anterior descending branch of the rat coronary artery, and SP alcohol extract was administered to evaluate its anti-myocardial ischemic effect. We analyzed the SP ingredients absorbed into the rats blood, screened the active compounds, established a database of SP anti-myocardial ischemic targets, and explored the possible mechanism of SP in treating myocardial infarction using bioinformatics. The rats were examined using echocardiography, serum biomarkers were determined, and pathological changes were observed by histopathological examination. TUNEL staining was performed to detect the apoptotic level of cells, and Western blot and quantitative real-time polymerase chain reaction were performed to detect the expression levels of Bcl-2, Bax, and Caspase-3 in heart tissues. In the fingerprint of SP, 24 common peaks were established, and the similarity evaluation results of 10 batches of SP were all >0.9. Ultra-performance liquid chromatography-Q Exactive-mass spectrometry and GC-MS detected 17 active ingredients in the drug-containing serum, including terpenoids, flavonoids, phenols, phenylpropanoids, and phenolic acids, the most abundant of which was resveratrol. Enrichment analysis of SP targets against myocardial ischemia revealed that key candidate targets of SP were significantly enriched in multiple pathways associated with apoptosis. Resveratrol was administered to the successfully modeled rats, and the results showed that the resveratrol group significantly decreased left ventricular end-diastolic diameter and left ventricular end-systolic diameter and significantly increased ejection fraction and fractional shortening in all groups compared with the model group. Resveratrol significantly decreased the levels of creatine kinase isoenzyme and lactate dehydrogenase in serum compared to the model group (P < 0.001). Hematoxylin-eosin staining of rat myocardial tissue showed that all lesions were reduced under microscopic observation in the resveratrol group compared with the model group. Real-time polymerase chain reaction and Western blot results showed that the resveratrol group downregulated the expression of the proapoptotic factor Bax, upregulated the expression of the antiapoptotic factor Bcl-2, and decreased the expression of Caspase-3. The established fingerprints are accurate, reliable, and reproducible and can be used as an effective method for quality control of the herbs. The anti-myocardial ischemia effect of SP is that resveratrol improves cardiac function and inhibits cardiomyocyte apoptosis to protect cardiomyocytes. The present study provides ample evidence for the clinical use of SP, suggesting that this drug has great potential in the treatment of ischemic heart disease.

Keywords: Syringa pinnatifolia; apoptosis; myocardial ischemia; resveratrol.

MeSH terms

  • Animals
  • Caspase 3 / metabolism
  • Caspase 3 / pharmacology
  • Caspase 3 / therapeutic use
  • Creatine Kinase
  • Eosine Yellowish-(YS) / metabolism
  • Eosine Yellowish-(YS) / pharmacology
  • Eosine Yellowish-(YS) / therapeutic use
  • Flavonoids / metabolism
  • Hematoxylin / metabolism
  • Hematoxylin / pharmacology
  • Hematoxylin / therapeutic use
  • Isoenzymes / metabolism
  • Isoenzymes / pharmacology
  • Isoenzymes / therapeutic use
  • Lactate Dehydrogenases / metabolism
  • Myocardial Infarction* / drug therapy
  • Myocardial Ischemia* / drug therapy
  • Myocardial Ischemia* / metabolism
  • Myocardium / metabolism
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / pathology
  • Plant Extracts / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / therapeutic use
  • Rats
  • Resveratrol
  • Syringa* / chemistry
  • Terpenes / metabolism
  • bcl-2-Associated X Protein / metabolism
  • bcl-2-Associated X Protein / pharmacology

Substances

  • Flavonoids
  • Isoenzymes
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • Terpenes
  • bcl-2-Associated X Protein
  • Lactate Dehydrogenases
  • Creatine Kinase
  • Caspase 3
  • Resveratrol
  • Eosine Yellowish-(YS)
  • Hematoxylin