Objective:To study the changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate（ANIT）-induced experimental hepatic injury after oral administration of Yinchenhao Decoction...Objective:To study the changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate（ANIT）-induced experimental hepatic injury after oral administration of Yinchenhao Decoction（茵陈蒿汤,YCHD） using an ultra pressure liquid chromatography（UPLC） method.Methods:Rats were divided into a normal group and a model group,after modeled by 4%ANIT（75 mg/kg） for 48 h,they were orally administrated with YCHD extract at the dose of 0.324 g/kg,and then blood was collected from their orbital sinus after different intervals.Changes in liver function were monitored by the levels of liver enzymes [alanine aminotransferase（ALT）,aspartate aminotransferase（AST）]and bilirubins[total bilirubin（TBIL）,direct bilirubin（DBIL）],the concentration of 6,7-dimethoxycoumarin in plasma were measured by UPLC,and the pharmaceutical parameters were calculated with DAS2.1.1 software.Results:The concentration-time curve of both normal and modeled rats after oral administration of YCHD was obtained.Their time to maximum plasma concentration(tmax) were both 0.25 h,the maximum concentration(Cmax) were 4.533μg/mL and 6.885μg/mL, and their area under concentration-time curve（AUC）0→24h were 16.272 and 32.981,respectively.There was a 51.88%and 100.46%increase in Cmax and AUC0-t（P<0.05）,but there showed a 45.52%and 92.93%reduction in clearance of drug and volum of distribution（P<0.05）,respectively.Conclusions:Hepatic injury could significantly influence the pharmacokinetics of 6,7-dimethoxycoumarin after oral administration of YCHD,the absorption and distribution process was accelerated in liver injured rats,but the metabolism and elimination process was slowed.And this may lead to a significant accumulation of 6,7-dimethoxycoumarin in the body.展开更多
Objective: To ascertain anti-fatigue constituents and mechanisms of Herpetospermum caudigerum. Methods: The 80% ethanol extracts of Herpetospermum caudigerum were partitioned with chloroform, ethyl acetate and n-butan...Objective: To ascertain anti-fatigue constituents and mechanisms of Herpetospermum caudigerum. Methods: The 80% ethanol extracts of Herpetospermum caudigerum were partitioned with chloroform, ethyl acetate and n-butanol, respectively. Male Kunming mice were divided into 13 groups with 16 mice in each group: a control group fed with water, 9 groups treated with 3 fractions of Herpetospermum caudigerum(chloroform fraction, ethyl acetate fraction and n-butanol fraction) at dose of 80, 160 and 320 mg/kg for the low-dose group, medium-dose group and high-dose group, 3 herpetrione(HPE) treated groups fed with HPE at dose of 15, 30, and 60 mg/kg for the low-dose group, medium-dose group and high-dose group. All animals were treated once per day for 30 days. Anti-fatigue activity was assessed through the forced swimming test and serum biochemical parameters including blood lactic acid(BLA), blood urea nitrogen(BUN), malondialdehyde(MDA), hepatic glycogen(HG), lactic dehydrogenase(LDH), superoxide dismutase(SOD) and glutathione peroxidase(GPx) determined following the recommended procedures provided by the commercial kits. Results: Compared with the control group, the lignans extract(ethyl acetate fraction) of Herpetospermum caudigerum and HPE could significantly prolonged the exhaustive swimming time(P<0.05 or P<0.01), and also increased the HG levels(P<0.05 or P<0.01) and the activities of antioxidant enzymes(SOD, GPx and LDH, P<0.05 or P<0.01); BLA and MDA levels were decreased considerably in lignans extract and HPE treated groups(P<0.05 or P<0.01). HPE also could significantly decrease the BUN contents compared with the control group(P<0.05). The chloroform and n-butanol fraction showed no effect on swimming time and biochemical parameters. Conclusions: The lignans extract had antifatigue activities and HPE may be partly responsible for the anti-fatigue effects of Herpetospermum caudigerum. The possible mechanisms of anti-fatigue activity were related to the decrease of BUN and BLA, the increase of the HG storage and protecting corpuscular membrane by preventing lipid oxidation via modifying several enzyme activities.展开更多
基金Supported by the National Natural Science Foundation of China (No.81073069)
文摘Objective:To study the changes of pharmacokinetics of 6,7-dimethoxycoumarin in a rat model of alpha-naphthylisothiocyanate（ANIT）-induced experimental hepatic injury after oral administration of Yinchenhao Decoction（茵陈蒿汤,YCHD） using an ultra pressure liquid chromatography（UPLC） method.Methods:Rats were divided into a normal group and a model group,after modeled by 4%ANIT（75 mg/kg） for 48 h,they were orally administrated with YCHD extract at the dose of 0.324 g/kg,and then blood was collected from their orbital sinus after different intervals.Changes in liver function were monitored by the levels of liver enzymes [alanine aminotransferase（ALT）,aspartate aminotransferase（AST）]and bilirubins[total bilirubin（TBIL）,direct bilirubin（DBIL）],the concentration of 6,7-dimethoxycoumarin in plasma were measured by UPLC,and the pharmaceutical parameters were calculated with DAS2.1.1 software.Results:The concentration-time curve of both normal and modeled rats after oral administration of YCHD was obtained.Their time to maximum plasma concentration(tmax) were both 0.25 h,the maximum concentration(Cmax) were 4.533μg/mL and 6.885μg/mL, and their area under concentration-time curve（AUC）0→24h were 16.272 and 32.981,respectively.There was a 51.88%and 100.46%increase in Cmax and AUC0-t（P<0.05）,but there showed a 45.52%and 92.93%reduction in clearance of drug and volum of distribution（P<0.05）,respectively.Conclusions:Hepatic injury could significantly influence the pharmacokinetics of 6,7-dimethoxycoumarin after oral administration of YCHD,the absorption and distribution process was accelerated in liver injured rats,but the metabolism and elimination process was slowed.And this may lead to a significant accumulation of 6,7-dimethoxycoumarin in the body.
基金Supported by the National Key New Drugs Innovation Foundation(No.2009ZX09103-349)the Beijing Natural Science Foundation(No.7122176)
文摘Objective: To ascertain anti-fatigue constituents and mechanisms of Herpetospermum caudigerum. Methods: The 80% ethanol extracts of Herpetospermum caudigerum were partitioned with chloroform, ethyl acetate and n-butanol, respectively. Male Kunming mice were divided into 13 groups with 16 mice in each group: a control group fed with water, 9 groups treated with 3 fractions of Herpetospermum caudigerum(chloroform fraction, ethyl acetate fraction and n-butanol fraction) at dose of 80, 160 and 320 mg/kg for the low-dose group, medium-dose group and high-dose group, 3 herpetrione(HPE) treated groups fed with HPE at dose of 15, 30, and 60 mg/kg for the low-dose group, medium-dose group and high-dose group. All animals were treated once per day for 30 days. Anti-fatigue activity was assessed through the forced swimming test and serum biochemical parameters including blood lactic acid(BLA), blood urea nitrogen(BUN), malondialdehyde(MDA), hepatic glycogen(HG), lactic dehydrogenase(LDH), superoxide dismutase(SOD) and glutathione peroxidase(GPx) determined following the recommended procedures provided by the commercial kits. Results: Compared with the control group, the lignans extract(ethyl acetate fraction) of Herpetospermum caudigerum and HPE could significantly prolonged the exhaustive swimming time(P<0.05 or P<0.01), and also increased the HG levels(P<0.05 or P<0.01) and the activities of antioxidant enzymes(SOD, GPx and LDH, P<0.05 or P<0.01); BLA and MDA levels were decreased considerably in lignans extract and HPE treated groups(P<0.05 or P<0.01). HPE also could significantly decrease the BUN contents compared with the control group(P<0.05). The chloroform and n-butanol fraction showed no effect on swimming time and biochemical parameters. Conclusions: The lignans extract had antifatigue activities and HPE may be partly responsible for the anti-fatigue effects of Herpetospermum caudigerum. The possible mechanisms of anti-fatigue activity were related to the decrease of BUN and BLA, the increase of the HG storage and protecting corpuscular membrane by preventing lipid oxidation via modifying several enzyme activities.
