The Study On Effectiveness Of Two Chinese Herbal Prescriptions Basised On The Bioavailability Of Active Ingredient In It

ObjectiveEffects of drugs and body is mutual. Reaching a certain blood concentration of drug is the premise of pharmacological activities. Chinese prescription can change the metabolism of active ingredients to regulate its plasma concentration and improve the bioavailability.In the basis of AD’s pathogenesis、clinical experience and experiment research, Bushen-Yizhi prescription is created by a team of Guangzhou University of Chinese Medicine, in which team professor Lai Shirong is the leader. Bushen-Yizhi prescription was proved to a potential therapeutic as well as its active ingredients osthole which is the main compound of Common Cnidium Fruit, the main drug of Bushen-Yizhi prescription.Danggui-Shaoyao-San from "Synopsis of Golden Chamber",a book of Zhang Zhongjing, previously mainly used in the treatment of gynecological pain syndrome, have been discovered in recent years on the role of the treatment of AD. Ferulic acid, one of the main compound of Danggui-Shaoyao-San was found to show a similar pharmacological activities in the treatment of AD, and is considered as the main active ingredient of Danggui-Shaoyao-San.The present study would investigate the effect of Bushen-Yizhi prescription (Danggui-Shaoyao-San) on the bioavailability of its active ingredient osthole (ferulic acid).MethodsAfter the extract of Bushen-Yizhi prescription (BSYZ) and Cnidium monnieri (L.) Cusson fruits (CM) were prepared, a HPLC-UV detection method for the determination of osthole in extract of BSYZ and CM was developed, and the the specificity, accuracy, precision, stability and so on were verify to determine the concentration of osthole in them. After the extract of BSYZ and CM were prepared, the content of ferulic acid in Danggui-Shaoyao-San (DSS) was determined by a developed and verified HPLC-UV method.A HPLC-UV detection method for the determination of osthole and ferulic acid in rat plasma were developed and verified, respectively.30rats were randomly assigned to five groups and orally administered with pure osthole at different doses (15,75and150mg/kg), CM (15mg/kg osthole) and BSYZ (15mg/kg osthole) extract. At different predetermined time points after administration, the concentrations of osthole in rat plasma were determined by using HPLC-UV method.10rats were randomly assigned to two groups and orally administered with pure ferulic acid at doses of0.406mg/kg and DSS (0.406mg/kg ferulic acid) extract. At different predetermined time points after administration, the concentrations of ferulic acid in rat plasma were determined by using HPLC-UV method. Main pharmacokinetic parameters were investigated with3P87software, and compared with one-way analysis of variance.ResultsAfter validation, the HPLC-UV method for the determination of osthole in extract of BSYZ and CM was meet the requirements of methodology for the determination of drug content in vitro. The content of osthole in BSYZ and CM were0.119%and0.431%respectively, and the content of ferulic acid in DSS was0.088%o.After validation, the HPLC-UV method for the determination of osthole and ferulic acid in rat plasma were meet the requirements of methodology for the determination of drug content in vivo. The concentration of osthole in rat plasma were determined and pharmacokinetic parameters were obtained which were significantly different among the groups. The AUC and Cmax of osthole were significantly increased after oral administration of BSYZ extract, followed by CM extract, in comparison to pure osthole at different doses. The concentration of ferulic acid in rat plasma were determined and pharmacokinetic parameters were obtained, which was turned out that ferulic acid could only be detemined within30mintue after oral adminstration of pure ferulic acid but within6h after oral adminstration of DSS with increased AUC and slowed absorption and elimination.Conelusion Osthole present first pass effect significantly after administration, and Bushen-Yizhi prescription was found to inhibit the first pass effect and improve its blood concentration and bioavailability, which probably as a result of the inhibition against CYP3A4, the enzyme metabolizing OST, caused by ginsenoside in Panaxginseng C. A. Mey. root and its metabolites and imperatorin in Cnidium monnieri (L.) Cusson fruits. The blood concentration of ferulic acid after oral administration was low, which could be determined only in half an hour after rapid absorption and elimination. Danggui-Shaoyao-San significantly inhibited the rapid absorption and elimination, and maintain the blood concentration, resulting in enhanced bioavailability. The mechanism were probably that gallic acid and benzoic acid, ingredients of Danggui-Shaoyao-San, inhibit absorption of ferulic acid through monocarboxylic acid transporter, and the other ingredients, levistilide A, coniferyl ferulate and alisol B inhibit efflux of ferulic acid in conjugate.Bushen-Yizhi prescription and Danggui-Shaoyao-San could enhance the bioavailability of its active ingredients, which illuminate the effectiveness of the two Chinese prescription from a new viewpoint that chinese herbal prescription obtained better effect by premoting the bioavailability of its active ingredients.