Objective:To evaluate the efficacy of Bawu Decoction(八物汤,BWD,Palmul-tang in Korean)against benign prostatic hyperplasia(BPH).Methods:Twenty-four male Wistar rats were divided into 4 groups,with 6 rats in each...Objective:To evaluate the efficacy of Bawu Decoction(八物汤,BWD,Palmul-tang in Korean)against benign prostatic hyperplasia(BPH).Methods:Twenty-four male Wistar rats were divided into 4 groups,with 6 rats in each group.The 4 study groups included sham-operated group(CON),BPH model group,finasteride-treated group,and BWD-treated group.All the groups except CON group received a subcutaneous injection of 10 mg/kg of testosterone,while CON group received saline.Finasteride at a dose of 5 mg/kg was administered to the finasteride-treated group for a period of 4 weeks.BWD group received BWD at a dose of 200 mg/kg for 4 weeks.The prostatic weight,prostate weight to body weight ratio,relative prostate weight ratio,serum testosterone and dihydrotestosterone(DHT)level,and histological analysis of prostatic tissue were analyzed.Results:Compared to BPH model group,BWD administration was associated with reductions in prostatic weight,prostate and relative prostate weight ratio weight to body weight ratio(P〈0.05).The concentration of serum testosterone and DHT were higher in BPH group compared with CON group(P〈0.05).Administration of finasteride and BWD suppressed the elevation of serum testosterone and DHT levels significantly(both P〈0.05).In addition,BWD suppressed the growth of prostatic tissue(P〈0.05).Conclusion:BWD has suppressant effects on development of BPH through inhibition of serum testosterone and DHT.展开更多
Objective:To assess the effects of traditional herbal formulae Sijunzi Decoction(四君子汤,Sagunja-tang,SJZD),Siwu Decoction(四物汤,Samul-tang,SWD),Bawu Decoction(八物汤,Palmul-tang,BWD)and Shiquan Dabu Decoctio...Objective:To assess the effects of traditional herbal formulae Sijunzi Decoction(四君子汤,Sagunja-tang,SJZD),Siwu Decoction(四物汤,Samul-tang,SWD),Bawu Decoction(八物汤,Palmul-tang,BWD)and Shiquan Dabu Decoction(十全大补汤,Sipjeondaebo-tang,SDD)on the activities of human cytochrome P450(CYP450),a drug-metabolizing enzyme.Methods:Herbal formula water extracts were filtered and lyophilized after the powder extracts were dissolved in distilled water.The activities of major human CYP450isozymes(CYP3A4,CYP2C19,CYP2D6 and CYP2E1)were measured using in vitro fluorescence-based enzyme assays.The inhibitory effects of the herbal formulas on the activities of CYP450 were characterized as half maximal inhibition concentration(IC50)values.Results:All the tested herbal formulae inhibited CYP2C19activity(IC50:SJZD,83.28μg/m L;SWD,235.54μg/m L;BWD,166.82μg/m L;SDD,178.19μg/m L);SJZD(IC50=196.46μg/m L),SWD(IC50=333.42μg/m L)and SDD(IC50=163.42μg/m L)inhibited CYP2E1-mediated metabolism;whereas BWD exhibited comparatively weak inhibition of CYP2E1(IC50=501.78μg/m L).None of the four herbal formulas significantly affected CYP3A4 or CYP2D6.Conclusions:These results suggest that SJZD,SWD,BWD and SDD could potentially inhibit the metabolism of co-administered synthetic drugs whose primary route of elimination is via CYP2C19.In addition,clinically relevant pharmacokinetic interactions could occur when SJZD,SWD or SDD is co-administered with drugs metabolized by CYP2E1.Our findings provide information for the safety and effective clinical use of these four classic herbal formulas.展开更多
Objective: To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib (Iressae) and the oriental medications Guipi Decoction (归脾汤, GPD, Guibi-tang in Korean) and Bawu Decoction ...Objective: To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib (Iressae) and the oriental medications Guipi Decoction (归脾汤, GPD, Guibi-tang in Korean) and Bawu Decoction (八物汤, BWD, Palmul-tang in Korean). Methods: Methylceliulose (MC, control), GPD (1,200 mg/kg), or BWD (6,000 mg/kg) was orally administered to rats either as a single dose or multiple doses prior to gefitinib administration. To examine the effects of a single dose of the herbal medicines, gefitinib (10 mg/kg) was orally administered after 5 min or 1 h of MC or the herbal medicine pretreatments. To examine the effects of the multiple doses of the herbal medicines, gefltinib (10 mg/kg) was orally administered following 7 consecutive days of the administration of MC or each herbal medicine. The plasma concentrations of gefitinib were determined with liquid chromatography-tandem mass spectrometry assay. The plasma concentration-time profiles of gefitinib were analyzed with a noncompartmental analysis. Results: Gefitinib was rapidly absorbed and showed a mono- exponential decline with an elimination half-life of 3.7-4.1 h. The pharmacokinetics of gefitinib was not affected by GPD pretreatment. However, a significantly lower maximum plasma concentration (Crux, P〈0.05) and area under the curve (P〈0.05), and a delayed time to reach Cmax (Tmax, P〈0.01) were observed in both single- and multiple- dose BWD-pretreated rats compared with the control rats. Conclusions: BWD and not GPD might delay and interfere with gefitinib absorption. Further evaluations of the clinical significance of these findings are needed.展开更多
基金Supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science,ICT & Future Planning(NRF-2016R1C1B2011827)
文摘Objective:To evaluate the efficacy of Bawu Decoction(八物汤,BWD,Palmul-tang in Korean)against benign prostatic hyperplasia(BPH).Methods:Twenty-four male Wistar rats were divided into 4 groups,with 6 rats in each group.The 4 study groups included sham-operated group(CON),BPH model group,finasteride-treated group,and BWD-treated group.All the groups except CON group received a subcutaneous injection of 10 mg/kg of testosterone,while CON group received saline.Finasteride at a dose of 5 mg/kg was administered to the finasteride-treated group for a period of 4 weeks.BWD group received BWD at a dose of 200 mg/kg for 4 weeks.The prostatic weight,prostate weight to body weight ratio,relative prostate weight ratio,serum testosterone and dihydrotestosterone(DHT)level,and histological analysis of prostatic tissue were analyzed.Results:Compared to BPH model group,BWD administration was associated with reductions in prostatic weight,prostate and relative prostate weight ratio weight to body weight ratio(P〈0.05).The concentration of serum testosterone and DHT were higher in BPH group compared with CON group(P〈0.05).Administration of finasteride and BWD suppressed the elevation of serum testosterone and DHT levels significantly(both P〈0.05).In addition,BWD suppressed the growth of prostatic tissue(P〈0.05).Conclusion:BWD has suppressant effects on development of BPH through inhibition of serum testosterone and DHT.
基金Supported by the Construction of Scientific Evidences for Herbal Medicine Formulae(No.K16251)Evaluation of Herb-Drug Interactions(No.K16252)from the Korea Institute of Oriental Medicine
文摘Objective:To assess the effects of traditional herbal formulae Sijunzi Decoction(四君子汤,Sagunja-tang,SJZD),Siwu Decoction(四物汤,Samul-tang,SWD),Bawu Decoction(八物汤,Palmul-tang,BWD)and Shiquan Dabu Decoction(十全大补汤,Sipjeondaebo-tang,SDD)on the activities of human cytochrome P450(CYP450),a drug-metabolizing enzyme.Methods:Herbal formula water extracts were filtered and lyophilized after the powder extracts were dissolved in distilled water.The activities of major human CYP450isozymes(CYP3A4,CYP2C19,CYP2D6 and CYP2E1)were measured using in vitro fluorescence-based enzyme assays.The inhibitory effects of the herbal formulas on the activities of CYP450 were characterized as half maximal inhibition concentration(IC50)values.Results:All the tested herbal formulae inhibited CYP2C19activity(IC50:SJZD,83.28μg/m L;SWD,235.54μg/m L;BWD,166.82μg/m L;SDD,178.19μg/m L);SJZD(IC50=196.46μg/m L),SWD(IC50=333.42μg/m L)and SDD(IC50=163.42μg/m L)inhibited CYP2E1-mediated metabolism;whereas BWD exhibited comparatively weak inhibition of CYP2E1(IC50=501.78μg/m L).None of the four herbal formulas significantly affected CYP3A4 or CYP2D6.Conclusions:These results suggest that SJZD,SWD,BWD and SDD could potentially inhibit the metabolism of co-administered synthetic drugs whose primary route of elimination is via CYP2C19.In addition,clinically relevant pharmacokinetic interactions could occur when SJZD,SWD or SDD is co-administered with drugs metabolized by CYP2E1.Our findings provide information for the safety and effective clinical use of these four classic herbal formulas.
基金Supported by the Comprehensive and Interactive Medicine InstituteNational Research Foundation of Korea(No.2012R1A2A2A02044997)
文摘Objective: To evaluate the potential pharmacokinetic interactions of the anticancer agent gefitinib (Iressae) and the oriental medications Guipi Decoction (归脾汤, GPD, Guibi-tang in Korean) and Bawu Decoction (八物汤, BWD, Palmul-tang in Korean). Methods: Methylceliulose (MC, control), GPD (1,200 mg/kg), or BWD (6,000 mg/kg) was orally administered to rats either as a single dose or multiple doses prior to gefitinib administration. To examine the effects of a single dose of the herbal medicines, gefitinib (10 mg/kg) was orally administered after 5 min or 1 h of MC or the herbal medicine pretreatments. To examine the effects of the multiple doses of the herbal medicines, gefltinib (10 mg/kg) was orally administered following 7 consecutive days of the administration of MC or each herbal medicine. The plasma concentrations of gefitinib were determined with liquid chromatography-tandem mass spectrometry assay. The plasma concentration-time profiles of gefitinib were analyzed with a noncompartmental analysis. Results: Gefitinib was rapidly absorbed and showed a mono- exponential decline with an elimination half-life of 3.7-4.1 h. The pharmacokinetics of gefitinib was not affected by GPD pretreatment. However, a significantly lower maximum plasma concentration (Crux, P〈0.05) and area under the curve (P〈0.05), and a delayed time to reach Cmax (Tmax, P〈0.01) were observed in both single- and multiple- dose BWD-pretreated rats compared with the control rats. Conclusions: BWD and not GPD might delay and interfere with gefitinib absorption. Further evaluations of the clinical significance of these findings are needed.