RÉSUMÉ
AIM To prepare the nanosuspensions of naringenin phospholipids complex,and to investigate their in vivo pharmacokinetics.METHODS High-pressure homogenization method was applied to preparing the nanosuspensions of phospholipids complex.With stabilizer type,stabilizer-phospholipids complex consumption ratio,homogeneous pressure and homogeneous frequency as influencing factors,particle size,PDI and Zeta potential as evaluation indices,the formulation was optimized by single factor test.The morphology was observed under transmission electron microscope,after which X-ray powder diffraction analysis was performed,solubility,oil-water partition coefficient,dissociation rate of phospholipids complex and accumulative release rate were determined.Twenty-four rats were randomly assigned into four groups and given intragastric administration of the 0.5%CMC-Na suspensions of naringenin and its phospholipids complex,nanosuspensions and nanosuspensions of phospholipids complex(30 mg/kg),respectively,after which blood collection was made at 0,0.25,0.5,1,1.5,2,3,4,5,6,8,10,12 h,HPLC was adopted in the plasma concentration determination of naringenin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be 50 mg for naringenin consumption,PVP K30+TPGS(1 ∶ 1)as stabilizer,3 ∶ 1 for stabilizer-phospholipids complex consumption ratio,100 MPa for homogeneous pressure,and 10 times for homogeneous frequency,respectively.The obtained spherical-like or oval nanosuspensions of phospholipids complex demonstrated the average particle size,PDI and Zeta potential of(260.53±25.86)nm,0.160±0.024 and(-31.08±1.37)mV,respectively.Naringenin existed in the nanosuspensions of phospholipids complex in an anamorphous state,along with increased solubility,oil-water partition coefficient and dissociation rate of phospholipids complex,and the accumulative release rate reached more than 90%within 4 h.Compared with raw medicine and nanosuspensions,the nanosuspensions of phospholipids complex displayed shortened tmax(P<0.05)and increased Cmax,AUC0-t,AUC0-∞(P<0.05,P<0.01),the relative bioavailability was enhanced to 4.38 times.CONCLUSION The nanosuspensions of phospholipids can enhance naringenin's solubility and dissolution rate,and promote its in vivo absorption.
RÉSUMÉ
<p><b>OBJECTIVE</b>To observe the dynamic expression changes of p38 mitogen-activated protein kinase (p38MAPK), nucler facter kappa B (NF-κB) and cyclooxygenase-2 (COX-2) in myocardial tissue after an exhausted exercise and study the impact of p38MAPK, NF-κB and COX-2 on its myocardial damage.</p><p><b>METHODS</b>Sixty Wister male rats were randomly divided into the control group (n = 10) and the exhausted exercise group (n = 50). Then the exhausted exercise group was further divided into 5 subgroups, namely 0 h, 3 h, 6 h, 12 h, 24 h after an exhausted exercise (n = 10). The myocardial injury animal model was set up by using an exhausted swimming exercise and the expression of p-p38MAPK, NF-κB and COX-2 were examined by Western blot.</p><p><b>RESULTS</b>Compared with the control group, the expression of p-p38MAPK were increased significantly (P < 0.01) in all the groups and the 3 h group was the highest( P < 0.01); The expression of NF-κB were increased significantly (P < 0.05) in all the groups but 0 h P > 0.05) and the 6h group was increased significantly compared with the other groups( P < 0.05); The expression of COX-2 were increased significantly( P < 0.05) in all the groups but 0 h and the 24 h groups was increased significantly compared with the other groups(P < 0.05).</p><p><b>CONCLUSION</b>p38MAPK was activated in an acute exhausted exercise, p-p38MAPK may play an important role in modulating NF-κB and COX-2 expression and mediating the exhausted exercise induced myocardial damage.</p>