Anti-myocardial ischemia effect of Syringa pinnatifolia Hemsl. by inhibiting expression of cyclooxygenase-1 and -2 in myocardial tissues of mice

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• 作者：Yuan Cao^a ; ^b ; ¹ ; Jing Wang^a ; ^b ; ¹ ; Guozhu Su^a ; ^b ; ¹ ; Yan Wu^c ; Ruifeng Bai^a ; ^b ; Qian Zhang^a ; Xiaoli Gao^a ; Chun Li^a ; ^{lichun19850204@163.com" class="auth_mail" title="E-mail the corresponding author} ; Suyile Chen^d ; Pengfei Tu^a ; Xingyun Chai^a ; ^{xingyunchai@yeah.net" class="auth_mail" title="E-mail the corresponding author}
• 关键词：SP ; Syringa pinnatifolia Hemsl. ; IHD ; ischemic heart disease ; LAD ; left anterior descending ; ASA ; acetylsalicylic acid ; LVEDs ; left ventricular end-systolic diameter ; LVEDd ; left ventricular end-diastolic diameter ; EF ; ejection fraction ; FS ; fractional shortening ; COX ; cyclooxygenase ; CK-MB ; creatine kinase-MB ; LDH ; lactate dehydrogenase ; TXA2 ; thromboxane A2 ; PG ; prostaglandin ; AA ; arachidonic acid ; HE ; hematoxylin-eosin ; NSAID ; nonsteroidal anti-inflammatory drugs
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：1 July 2016
• 年：2016
• 卷：187
• 期：Complete
• 页码：259-268
• 全文大小：4926 K

文摘

The peeled stem of Syringa pinnatifolia Hemsl. (SP) is a traditional medicine in Inner Mongolia, China. The powder form of SP has been widely used for hundreds of years to relieve “He-Yi” related myocardial ischemia independently or in a traditional Chinese medicine preparation.

Materials and methods

SP was extracted with 95% and 80% ethanol. Chemical profiling was performed using HPLC-DAD and IT-TOF-ESI-MS analyses. Myocardial ischemia was produced by ligation of the left anterior descending (LAD) coronary artery to evaluate the anti-myocardial ischemia effect of SP. Male C57BL/6 mice were randomly divided into six groups (n=10 per group): a sham group, a model group, groups pretreated with SP at three dosages (20 mg/kg, 40 mg/kg, and 80 mg/kg, intragastrically), and a positive control group (acetylsalicylic acid, ASA, 53 mg/kg, intragastrically). Echocardiography was performed to determine heart function by measuring ejection fraction and fractional shortening. The levels of creatine kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in serum, and 6-keto-PGF₁α and TXB₂ both in plasma and in protein homogenate of myocardial tissue were also measured. The levels of cyclooxygenase (COX)-1 and -2 in the heart tissue and their expressions in mouse myocardial tissue were determined using Western blot and an immunofluorescence assay, respectively. Inflammatory cell infiltration and collagen deposition changes in the myocardial ischemic tissue were observed by pathological examination.

Results

Intragastric pretreatment with SP produced a dose-dependent increase in cardiac function. SP at 80 mg/kg significantly improved the EF (p<0.001) and FS (p<0.01) compared with the model group, as well as the levels of serum CK-MB and LDH decreased obviously (p<0.001), approaching those in the sham group. Besides, an obvious reduction in inflammatory cells infiltration and collagen deposition in the infarcted myocardial tissue was shown in each SP treatment group. In addition, SP increased 6-keto-PGF₁α and decreased TXB₂ levels in the plasma, whereas the opposite pattern was observed in the protein homogenate from the myocardial tissues at the infarction edge, but keeping balance the ratio of 6-keto-PGF₁α and TXB_2, which is better than ASA in plasma. The mechanisms is associated with the downregulated expressions of COX-1 (p<0.05) and COX-2 (p<0.001).

Conclusions

Ethanol extract of SP has a protective effect against myocardial ischemia via down regulation of COX-1 and COX-2 expression and by adjusting the ischemia-induced imbalance between 6-keto-PGF₁α and TXB₂. This study shows substantial evidence to support the clinical application of SP and indicates that such medicine has great potential for treating ischemia-induced heart disease.