| Dihydroquercetin belonged to flavanonol and it could be extracted from sibirica Lcdeb?Distylium racemosum.It had many important biological activities.It could inhibit and activate a variety of enzymes,lower blood pressure,widen coronary artery,clear LDL.It had a protective effect on myocardial ischemia-reperfusion injury,had a therapeutic effect against diabetes and heart disease as well as irresistibleeffect on apoptosis of myocardial cells by high glucose-induced.The research team according to early studies found that dihydroquercetin has good protection on myocardial ischemia caused by isoproterenol.In order to further explore the mechanism of its anti-ischemic effects on the cellular level,this article established oxidative damage model induced by H2O2in H9c2 cardiomyoblasts,make a thorough inquiry protective effect by dihydroquercetin on myocardial cell injury and its mechanism.A model of H2O2-induced injury in H9c2 cardiomyoblasts was established to investigate the protective effects of dihydroquercetin against H2O2-induced injury in H9c2 cardiomyoblasts.Cell viability was determined col ori metrically by3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium(MTT)assay.The supernate and the cells were collected,respectively,after the different treatments for measuring the LDH and MDA levels,as well as SOD,CAT and GSH-Px activity with the corresponding detection kit according to the manufacturer's instructions.H9c2 cardiomyoblasts were pretreated with dihydroquercetin for 12 h before exposure to 150 ?M for 6 h.H2O2 treatment caused severe injury to H9c2 cardiomyoblasts.Dihydroquercetin pretreatment could attenuate H2O2-induced injury,decrease the levels of LDH leakage and MDA,and increase the activities of SOD,CAT,and GSH-Px with a dose-dependent.Dihydroquercetin showed significant protective effects against H2O2-induced injury in H9c2 cardiomyoblasts in dose-dependent.The mechanism of this may be due to its increasing the activities of endogenous antioxidant enzymes,as well as improving the stabilization of myocardial cells.Pharmacological studies showed that:As dihydroquercetin contained more phenolic hydroxyl group,resulted in antioxidant,anti-radiation effects.It was also used as food additives for industry.In addition,it also had anti-viral and anti-tumor activities However,dihydroquercetinwas hard to dissolve,lower bioavailabilityanomalous oral absorption which constrained its application on clinical application.The experiment made dihydroquercetin into solid dispersion tablets,dihydroquercetin and its solid dispersion tablets were both in vivo pharmacokinetics which conducted a preliminary study to lay the foundation for further development of dihydroquercetin.This study was based on preliminary pharmacodynamics,extraction,refining,preparation process,since,we choose pvpk30 as drug carrier,the ratio of drug and carrier was 1:6,Direct powder compression method was used to prepare solid dispersion tablets,pharmacokinetic study was conducted on its SD tablets.Plasma samples were extracted by ethyl acetate,and the supernatant was evaporated to dryness,reconstituted by methanol,subsequently injected into electrospray tandem mass spectrometry(LC-MS/MS),dihydroquercetin and its SD tablets which were in the blood components were identified under reflecting the multi-monitor mode anion[multiple reaction monitoring(MRM))].The molecular weight of Dihydroquercetin 304.0 was cracked into smaller molecules of 285.0.The molecular weight of internal standard(butylparaben)was cracked from 193.1 into 92.0.Plasma concentration of dihydroquercetin and its SD tablets after oral administration was linear within 5?4280 n g/m L,extraction recoveries were all more than 75%,intra-day and inter-day precision were both less than 8%,all above were compliance with the analysis requirements of biological sample.Wistar male rats were used for pharmacokinetic studies,pharmacokinetic parameters were calculated by DAS software.Oral administration of there doses 15mg/kg,30mg/kg,60 mg/kg,respectively,of dihydroquercetin and its solid dispersion tablets,results showed that the area under the plasma curve of dihydroquercetin and its SD tablets were 1461.3 ± 265.1(ng min/mL),13362.3 ± 4761.3(ng min/mL),45464.8 ± 19532.4(ng min/mL);2186.5 ± 302.6(ng min/mL),16836.5 ± 3256.2(ng min/mL),52739.2 ± 11038.7(ng min/mL),maximum blood concentrations were 89.9 ± 26.2(ng/mL),820.6±102.9(ng/mL),2275.4 ± 288.0(ng/mL);132.5 ± 18.6(ng/mL),955.6±174.4(ng/mL),2842.9 ± 631.4(ng/mL),a single dose of dihydroquercetin 15mg/kg after intravenous administration,its area under the plasma curve was 673514.8±76357.3(ng min/mL),their absolute bioavailability were 0.165%,0.296%,respectively.times to peak were 7.8±0.3min,8.3±1.5min,13.5±1.9min;8.9±0.5min,9.8±1.6min,15.2±2.8min,respectively.Results show that dihydroquercetin SD tablets were rapidly absorbed,rapid onset,high blood concentration. |
PDF Full Text Request