| Fructus Schisandra is derived from the dry ripe fruit of Schisandra chinensis(Turcz.)Baill,with shou lian gu se,yi qi sheng jin,bu shen ning xin effects.The vinegar processed one can enhance effect of suan lian shou se and bao gan hu gan.But about the vinegar mechanism of S.chinensis,the existing researches focused on the changes of the main active components,while the changes of the pharmacokinetics were barely reported.The topic was provided by Educational Commission of Jiangsu Province "vinegar manufacturing and processing mechanism of hepatic effects of traditional Chinese medicine study(NO.09KJA360001)".S.chinensis,the vinegar representative drug,was chosen for study object.Lignans,the main active ingredients,were chosen for study index,including Schisandrin,Deoxyschisandrin and Schisandrin B.Liver cell absorption,pharmacokinetics,tissue distribution and biliary excretion were selected for the study of the crude and vinegar-processed S.chinensis using HPLC-MS system from the level of cell and molecular.The results can help to understand the change rule of S.chinensis in rat,investigate the vinegar-processed metabolism of S.chinensis and guide the clinical usage of crude,vinegar-processed and products of S.chinensis.Effects of S.chinensis were processed with vinegar on liver cell absorption:The toxicity of the extract of the crude and vinegar-processed S.chinensis to liver cell measured with MTT.results showed that cell viability go to balance first and then down with the concentration increasing after given the extract of the crude and vinegar-processed S.chinensis,indicated that S.chinensis has cell toxicity at high concentration.But at low concentration,the viability of liver cell exceed 100%,indicated that S.chinensis may promote the proliferation of cell.From the trend chart,the cell viability of the vinegar-processed is higher than the crude,suggested that the cell toxicity of S.chinensis was decreased by processed with vinegar,especially at high concentration.Deoxyschisandrin and Schisandrin B can't be determined in L-02 cell cultured with extract of crude S.chinensis,but they can be quantitied accurately in L-02 after cultured with extract of vinegar-processed S.chinensis.The result indicate that the absorption of two lignans from S.chinensis in liver cell was promoted by processed of S.chinensis with vinegar.Schisandrin,the highest content lignans in S.chinensis,was determined in L-02 cell,and the reasons were further reseach next.Pharmacokinetic studies of S.chinensis:A HPLC-MS method was developed and vali for pharmacokinetic studies of three main active lignans in S.chinensis in rat plasma,incl Schisandrin,Deoxyschisandrin and Schisandrin B.The results showed that the method conforms to the guiding principles of determination of biosamples.The studied'all showed excellent linearity(r>0.9990)in the determined linear range in rat plasma.studied compartment modes of Schisandrin,Deoxyschisandrin and Schisandrin B were fitted to one-component model,and the pharmacokinetic parameters of three studied lignans were followed respectively:T1/2 1.95±0.26,8.30±3.36 and 5.31±0.68 h;Tmax 4.671±0.26,4.33±0.26 and 4.08±0.20 h;Cmax 0.54±0.07,0.23±0.07 and 0.40±0.04 mg·L-1.Also there were second absorb peak of the three studied lignans from their concentration-time carve.Effects of S.chinensis was processed with vinegar on tissues distribution in rat:according to the pharmacokinetic results,three different time points(distribute phase,equilibrium phase and eliminate phase)were chosen for the study of tissues distribution.A HPLC-MS method was developed and validated for pharmacokinetic studies of three main active lignans in S.chinensis in rat plasma,including Schisandrin,Deoxyschisandrin and Schisandrin B.The results showed that the developed method conforms to the guiding principles of determination of biosamples.The studied lignans all showed excellent linearity(r>0.9990)in the determined linear range in rat liver,heart,spleen,lung and kidney.Three lignans were distributed widely in rat tissues,including liver,heart,spleen,lung and kidney.The concentration of the three studied lignans was high in rat liver and lung,followed by kidney and heart,and spleen was lowest.In determined times,the distribute trends of three studied lignans in rat tissues were changed after S.chinensis was processed with vinegar.Rats were oral administration given crude S.chinensis,the three lignans were distributed to balance rapidly in rats,and showed downward trend in the determine times.While rats were oral administration given vinegar-processed S.chinensis,the three lignans were distributed slowly in rat,the distribution trend was showed increased and then decreased,and the concentration of tissues distribution was higher than crude group.The results suggesting that after S.chinensis was processed with vinegar,can promote the distribution oflignans in S.chinensis in rat tissues,delay the peak time of lignans in S.chinensis in rat tissues,and extend the reside time of lignans in S.chinensis in rat.Effects of S.chinensis was processed with vinegar on biliary excretion in rat:after oral administration of crude and vinegar-processed S.chinensis to rat,there was significant difference on the crude group compared with the blank group,significant distinct difference on the vinegar-processed group compared with the blank group,and significant distinct difference on the vinegar-processed group compared with the crude group.It describes that vinegar-processed products can promote biliary excretion in rat.In summary,the research selected the crude and vinegar-processed S.chinensis as studied object.Lignans,the main active ingredients of S.chinensis,were studied on pharmacokinetic,including liver cell absorption,pharmacokinetics,tissues distribution,and biliary excretion.HPLC-MS methods were developed and validated for determination three main active lignans in S.chinensis in liver cell,in rat plasma and in rat liver,heart,spleen,lung,kidney,respectively.The results showed that after S.chinensis was processed with vinegar,can decrease the toxicity of liver cell,promote the tissues distribution in rat of the studied lignans and promote the biliary excretion of rat.This research can provide theoretical supporting for the vinegar processed of S.chinensis and reference for the theory of traditional Chinese medicine. |
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