| The prevalence of cardiovascular risk factors in China is obvious,leading to an increase in the number of patients suffered from cardiovascular disease.The prevalence and mortality of cardiovascular diseases in China are still on the rise,accounting for more than 40%deaths of residents caused by diseases.In recent years,the increasing burden of cardiovascular disease in our country has become a major public health problem and searching for a kind of medicine from traditional medicine resources that can effectively treat ischemic heart disease has been an important part of drug research for cardiovascular diseases.As a representative Mongolian medicine,Syringa pinnatifolia Hemsl.(SP),belonging to the family Oleaceae,is a deciduous shrub mainly distributed amongst the shrubs and spinneys of Helan Mountain,Inner Mongolia,China.The peeled stem,named ’Shan-chen-xiang’ in Chinese,has been employed as a traditional medicine for hundreds of years in Inner Mongolia,China,for the treatment of cardiovascular symptoms,asthma,pain,and fever.Our group conducted a preliminary study on the anti-ischemic effect of ethanol total extract(T)of SP,and for the first time revealed its mechanism on PGI2/TXA2 by regulating the expression of cyclooxygenase(COX).Based on the previous study,on the one hand,T was performed to obtain a major fraction(M)of 80%of the total extract quality and a secondary fraction(N)of 20%of the total extract quality,and efficacy evaluation of M and T was conducted to compare their activities.On the other hand,apoptosis mechanism of anti-ischemic myocardial ischemia was detected,and chemical composition and studies in vitro were also conducted.The following results were obtained:Review chapter describes two important pathological mechanisms in acute myocardial infarction(AMI):inflammation and apoptosis.Myocardial inflammation is a common pathological manifestation in current cardiovascular disease,including coronary heart disease and heart failure.A variety of inflammatory cells migrate to the infarct area,and certain signaling pathways within the cardiomyocytes will be activated in the process such as the COX pathway in the arachidonic acid(AA)metabolic pathway,causing a series of inflammatory cascade reactions.In addition,myocardial ischemia and hypoxia after myocardial infarction will lead to myocardial apoptosis,for example,through the regulation of Bax/Bcl-2 ratio of mitochondrial apoptosis pathway and death receptor pathways such as Fas/FasL.The presence of myocardial apoptosis not only expands the scope of myocardial infarction size,but also triggers the occurrence of ventricular remodeling and cardiac function deterioration.This review provides a reference for the mechanism of SP in preventing myocardial ischemia.Evaluation and comparison of anti-ischemic efficacy of T,M,and N:In vivo efficacy evaluation:acute myocardial ischemia models were prepared by ligation of LAD coronary artery in mice,and then the mice were intragastrically adiministrated of T,M,and N for seven days consecutively.The results showed that T and M could reduce LVEDs and LVEDd and improve cardiac EF and FS,thus effectively improving cardiac function.Decrease of the serum CK-MB,LDH,and hs-CRP and significant inhibition of infiltration of inflammatory cells in the marginal zone of myocardial infarction showed protective effects on ischemic heart.In vitro efficacy evaluation:Hypoxia model of H9c2 cells was prepared by Tri Gas incubator,and the anti-ischemic efficacy of T,M,and N was evaluated under hypoxia and serum-free conditions.The CCK8 assay showed that both T and M could significantly improve cell viability.The above results clearly demonstrated the equivalent anti-myocardial ischemic efficacy of T and M,however,M was at a lower dose and showed lower toxicity than T.Anti-myocardial ischemic mechanism of M:Western blot was used to detect expressions of apoptotic proteins in p53-mediated mitochondria apoptosis pathway in myocardial tissue and the result showed that M could reduce the content of p53 and decrease the ratio of Bax/Bcl-2,cleaved Caspase-3/Caspase-3 and cleaved Caspase-9/Caspase-9.qRT-PCR detection found that there was a significantly down-regulation of the p53 mRNA level in M-administrated group.The apoptosis of cells and the activity of Caspase-3 were detected by flow cytometry.The results showed M could significantly inhibit the apoptosis of cells in a dose-dependent manner.Compared with the model group,the fluorescence intensity of the administration group was significantly reduced in immunofluorescence assay.Preparation process and chemical characterization of different parts of T,M,and N:N was obtained through 30%ethanol elution and then M was obtained through 95%ethanol elution after HP-20 macroporous resin adsorption.The LC-MS-IT-TOF analysis and comparison of the monomer compounds isolated at the earlier stage in our group were performed on the chemical characterization and chromatographic peak identification of M.The results showed that M contains mainly lignans and sesquiterpenoids..Studies In vitro:LPS-induced inflammation model of RAW264.7 cells,conditional supernatant-induced inflammation model of H9c2 cells,H2O2-induced oxidative damage model of H9c2 cells,and hypoxia model of H9c2 cells were used to evaluate the activities of T,M,N,and some monomer compounds.The results showed that T,M,and some compounds exerted an ameliorating effect on inflammation,hypoxia,and oxidative damage of cardiomyocytes,especially M with the most significant effect,and provided a basis for further tracking of monomers or components that exert anti-ischemic effects and some evidence for the pharmacology of SP,however,the corresponding mechanisms need to be further explored.In brief,we considered that the mechanisms of myocardial protective effects of T and M in AMI were related to inhibition of inflammation and apoptosis.LC-MS-IT-TOF analysis and comparison with monomer compounds showed that the medicinal substances of SP were mainly in the medium and small polar parts.This study is one of the important parts for further refinement of drug efficacy sites and further determination of effective substances exhibits anti-myocardial ischemia effects.It provides a scientific basis for the clinical application of SP in ischemic heart disease and some reference for drug research on ischemic heart disease. |
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