无梗五加果化学成分分析和chiisanogenin的药动学研究
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摘要
无梗五加Acanthopanax sessiliflorus(Rupr.Et.Maxim)Seem.为五加科五加属植物,主产于中国、韩国和日本等地,具有滋补强壮、祛风除湿的功效。无梗五加果为无梗五加的成熟干燥果实,本论文对无梗五加果的化学成分、药理活性、分析方法和活性成分chiisanogenin的药物动力学进行研究。
采用大孔吸附树脂柱色谱、硅胶柱色谱、Sephadex-LH20柱色谱、ODS开口柱色谱及制备-HPLC等分离手段从无梗五加果70%乙醇提取物中分离得到了40个化合物,通过理化性质、1D-NMR、2D-NMR、MS等光谱手段,对40个化合物进行了鉴定。其中三萜类化合物1 2个:分别为3-O-[(α-L-arabinopyranosyl)(1→2)]-[-β-D-glucuronopyranosyl-6-O-methyl ester]-olean-12-ene-28-olic acid(1),(1R,11α,22α)1,4-epoxy-11,22-hydroxy-3,4-secolupane-20(30)-ene-3,28-dioic acid(2),(1R,11α)1,4-epoxy-11-hydroxy-3,4-secolupane-20(30)-ene-3,28-dioic acid(3),22α-hydroxychiisanogenin(5),chiisanogenin(6),oleanolic acid(7),oleanolic acid 3-O-β-D-glucopyranoside(8),oleanolic acid 3-O-6'-O-methyl-β-D-glucuronopyranoside(9),momordin Ib(10),chiisanoside(11),22α-hydroxy-chiisanoside(12),kalopanax saponins E(13);木脂素类化合物5个:分别为(-)-sesamin(14),simplexoside(15),(+)-syringaresinol-O-β-D-glucopyranosi-de(16),(-)-pinoresinol-4,4'-di-O-β-D-glucopyranoside(17),acanthoside D(18);香豆素类化合物4个:分别为scopoletin(19),scopolin methyl ether(20),isofraxidin(21),scopolin(22);黄酮类化合物2个:分别为quercetin(23),hyperin(24):单萜类化合物2个:为别为(3Z,6E)-3,7-dimethylocta-3,6-diene-1,2,8-triol(27),(E)-7-methyl-3-methyleneoct-6-ene-1,2,8-triol(28);酚酸类化合物11个:分别为niduloic acid(4),protocatechuic acid(25),protocatechuic acid methyl ester(26),tyrosol(29),p-hydrocoumaric acid(30),protocatechuic aldehyde(31),caffeic acid(32),4-(3,4-dihydroxyphenyl)-2-butanone(33),gallic acid(34),4-hydroxy-benzoic acid(35),pyrocatechol(36);糖类化合物2个:分别为蔗糖(37)和果糖(38);甾体类化合物2个:分别为胡萝卜苷(39)和β-谷甾醇(40)。其中化合物1、2、27、28为新化合物:化合物3、4为新天然产物;化合物15,17,19,20,22,26,33为首次从五加科植物中分离得到;化合物9,23,30为首次从五加属中分离得到;化合物5,7,8,10,13,29,35,36为首次从该植物中分离得到。
采用Born比浊法测定了3个三萜类化合物的体外抗血小板凝集活性。以DMSO为空白对照,以Aspirin为阳性对照,考察了3个三萜类化合物抗ADP诱导的体外血小板凝集活性,结果表明,3个化合物均有明显的抗ADP诱导的血小板凝集活性,其抗血小板凝集的强度与Aspirin接近。采用同样的方法考察了无梗五加果70%乙醇提取物在大鼠体内抗血小板凝集作用。结果表明,大鼠连续给予无梗五加果70%乙醇提取物(125,250,500,1000 mg/kg)15天后,大鼠的富血小板血浆(PRP)具有显著的抗ADP诱导的血小板凝集活性,在本文研究的剂量范围内呈剂量依赖性关系。采用大鼠动-静脉旁路循环模型进行无梗五加果70%乙醇提取物体内抗血栓的作用研究。结果表明,大鼠连续给予无梗五加果70%乙醇提取物(125,250,500,1000 mg/kg)15天后,动-静脉旁路循环模型的血栓湿重均有显著的降低,且各剂量的血栓湿重之间也均有显著性差异(P<0.05),在本文研究的剂量范围内呈剂量依赖性关系。
采用UPLC-ESI-MS/MS法同时测定了无梗五加果中10种三萜类成分的含量。色谱柱为ACQUITY UPLC~(TM) BEH C_(18) column(1.7μm,100 mm×2.1 mm,i.d.);流动相为5mmol/L醋酸铵水溶液(A)-乙腈(B),梯度洗脱;流速为0.25 mL/min;采用负离子检测方式,MRM扫描模式。10个三萜类成分在相应的线性范围内均呈良好的线性关系。应用该方法测定了无梗五加不同成熟期的果实中10个成分的含量,结果表明不同成熟期的无梗五加果中,10个成分的含量变化趋势各不相同,齐墩果酸及其苷类成分随着果实的不断成熟,在果实中的含量均呈平缓的上升趋势;开环羽扇豆烷型三萜苷类成分chiisanoside随着无梗五加果实的成熟,其在果实中的含量呈明显的下降趋势,而其苷元chiisanogenin则表现出明显的上升趋势,这种趋势可能是由苷断裂糖链逐渐转化成其苷元chiisanogenin导致的。本文所建立的分析方法专属、准确、灵敏、高效,为无梗五加果药材的质量评价提供了新的方法。
建立了测定大鼠血浆中chiisanogenin的UPLC-ESI-MS/MS分析方法。采用液-液萃取法进行血浆样品预处理,色谱柱为ACQUITY UPLC~(TM) BEH C_(18) column(1.7μm,50min×2.1 mm,i.d.);流动相为5 mmol/L醋酸铵水溶液-乙腈(10:90,v/v),等度洗脱;采用负离子检测方式,MRM扫描模式。利用该法分别研究了大鼠灌胃给予高、中、低3个剂量的单体chiisanogenin和相当于低剂量chiisanogenin的无梗五加果70%乙醇提取物后的药物动力学行为。统计学检验结果表明,在所研究的剂量范围内,chiisanogenin在大鼠体内呈线性药物动力学特征。与给药单体chiisanogenin相比,给药无梗五加果70%乙醇提取物后的AUC_(0-t)降低(P<0.05);大鼠血浆中chiisanogenin的药-时曲线出现双吸收峰现象,这种现象可能是由无梗五加果中存在的chiisanogenin的糖苷类成分在大鼠体内发生降解后转化成被测组分引起的。无梗五加果中其他成分影响了chiisanogenin的药动学行为。
Acanthopanax sessiliflorus(Rupr.et Maxim) Seem,belongs to Acanthopanax genus of the family Araliaceae.It is a shrub distributes mainly in China,Korea and Japan.It has traditionally been used as a tonic and a sedative,as well as in the treatment of rheumatism and diabetes.The chemical constituents,activities,analytical methods of Acanthopanax sessiliflorus fruits and pharmacokinetics of chiisanogenin were investigated in this study.
The chemical constituents of 70%ethanol extract of Acanthopanax sessiliflorus fruits were isolated by using multiple column chromatographic techniques,and 40 compounds were obtained.The structures of 40 compounds were fully elucidated by chemical and spectroscopic methods(1D,2D-NMR,MS).The identified compounds include twelve triterpenes:3-O-[(α-L-arabinopyranosyl)(1→2)]-[β-D-glucuronopyranosyl-6-O-methyl ester]-olean-12-ene-28-olic acid(1),(1R,11α,22α) 1,4-epoxy-11,22-hydroxy-3, 4-secolupane-20(30)-ene-3,28-dioic acid(2),(1R,11α)1,4-epoxy-11-hydroxy-3, 4-secolupane-20(30)-ene-3,28-dioic acid(3),22α-hydroxychiisanogenin(5),chiisanogenin (6),oleanolic acid(7),oleanolic acid 3-O-β-D-glucopyranoside(8),oleanolic acid 3-O-6'-O-methyl-β-D-glucuronopyranoside(9),momordin Ib(10),chiisanoside(11), 22a-hydroxychiisanoside(12),kalopanax saponins E(13);five lignans:(-)-sesamin(14), simplexoside(15),(+)-syringaresinol-O-β-D-glucopyranoside(16),(-)-pinoresinol-4, 4'-di-O-β-D-glucopyranoside(17),acanthoside D(18);four coumarins:scopoletin(19), scopolin methyl ether(20),isofraxidin(21),scopolin(22);two flavonoids:quercetin(23), hyperin(24);two monoterpenes:(3Z,6E)-3,7-dimethylocta-3,6-die-ne-1,2,8-triol(27), (E)-7-methyl-3-methyleneoct-6-ene-1,2,8-triol(28);eleven phenolic compounds:niduloic acid(4),protocatechuic acid(25),protocatechuic acid methyl ester(26),tyrosol(29), p-hydrocoumaric acid(30),protocatechuic aldehyde(31),caffeic acid(32),4-(3, 4-dihydroxyphenyl)-2-butanone(33),gallic acid(34),4-hydroxy-benzoic acid(35), pyrocatechol(36);tow sugars:sucrose(37),fructose(38);two steroids:daucosterol(39),β-sitosterol(40).Among them,four(1,2,27 and 28) were identified as new compounds, compounds 3 and 4 were identified as novel natural compounds;compounds 15,17,19,22, 26 and 33 were isolated from the family of Araliaceae for the first time;compounds 9,23 and 30 were isolated from the Acanthopanax genus for the first time;compounds 5,7,8,10,13, 29,35 and 36 were isolated from this plant for the first time.
The inhibitory activity on rat platelet aggregation induced by ADP in vitro of the two new compounds and a new natural product was tested by Born-nephelometer which was compared with that of aspirin(ASA).The three compounds showed excellent antiplatelet aggregation activity,which was almost equally potent to ASA.Platelet aggregation induced by ADP and thrombus weight in an arteriovenous thrombosis model were tested after 15 days treatment with 125,250,500 and 1000 mg/kg extract of Acanthopanax sessiliflorus fruits orally in rats, compared with 27 mg/kg ASA.The extract of Acanthopanax sessiliflorus fruits dose-dependently inhibited ADP induced platelet aggregation in vivo.Compared to a control thrombus weight of 108.1±2.7 mg,thrombus weight was 91.4±3.5,76.6±6.5,61.0±6.5 and 46.2±3.9 mg after treatment for 15 d with 125,250,500 and 1000 mg/kg(P<0.05) extract of Acanthopanax sessiliflorus fruits,respectively.Meanwhile,the thrombus weight was 62.9±6.7 mg after the treatment with 27 mg/kg of ASA.A dose-dependent relationship of anti-thrombotic effect was observed for the extract of Acanthopanax sessiliflorus fruits.
A UPLC-ESI-MS/MS method was developed for simultaneous quantitative determination of ten triterpenes in Acanthopanax sessiliflorus fruits.The analysis was performed on an ACQUITY UPLC~(TM)BEH C_(18) column(1.7μm,100 mm×2.1 mm,i.d.) using gradient elution with the mobile phase consisting of 5 mmol/L ammonium acetate in water and acetonitrile. The flow rate was 0.25 mL/min.The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring(MRM) mode via electrospray ionization (ESI) source.The method provided good accuracy and good precision and has been successfully applied to quantitative determination of ten compounds in the fruits from different fruits maturation periods.The contents of those compounds in samples from different fruits maturation periods varied significantly.
Chiisanogenin is an active compound of Acanthopanax sessiliflorus fruits with various pharmacological effects such as anti-platelet aggregation and anti-inflammatory effects.A specific,simple and sensitive UPLC-ESI-MS/MS method was developed and validated for the pharmacokinetic study of chiisanogenin in rat plasma.Chiisanogenin,with paracetamol as the internal standard,was extracted from plasma samples by liquid-liquid extraction.The analysis was carried out on an ACQUITY UPLC~(TM)BEH C_(18) column(1.7μm,50 mm×2.1 mm,i.d.) with mobile phase of acetonitrile-water containing 5 mmol/L ammonium acetate(90:10,v/v). The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring(MRM) mode via electrospray ionization(ESI) source.This validated method was successfully applied to a pharmacokinetic study in rats after oral administrations of chiisanogenin and the extract of Acanthopanax sessiliflorus fruits.Chiisanogenin showed a linear pharmacokinetics in rats in the studied dose range.Compared with the same dose of chiisanogenin,the AUCo-t of extract of Acanthopanax sessiliflorus fruits was decreased.The pharmacokinetic characteristic of the double peak in the plasma concentration-time curve of chiisanogenin may be attributed to the in vivo transforming of chisanoside into chiisanogenin. It was indicated that pharmacokinetic characteristic of chiisanogenin was affected by other constituents in extract of Acanthopanax sessiliflorus fruits.
采用大孔吸附树脂柱色谱、硅胶柱色谱、Sephadex-LH20柱色谱、ODS开口柱色谱及制备-HPLC等分离手段从无梗五加果70%乙醇提取物中分离得到了40个化合物,通过理化性质、1D-NMR、2D-NMR、MS等光谱手段,对40个化合物进行了鉴定。其中三萜类化合物1 2个:分别为3-O-[(α-L-arabinopyranosyl)(1→2)]-[-β-D-glucuronopyranosyl-6-O-methyl ester]-olean-12-ene-28-olic acid(1),(1R,11α,22α)1,4-epoxy-11,22-hydroxy-3,4-secolupane-20(30)-ene-3,28-dioic acid(2),(1R,11α)1,4-epoxy-11-hydroxy-3,4-secolupane-20(30)-ene-3,28-dioic acid(3),22α-hydroxychiisanogenin(5),chiisanogenin(6),oleanolic acid(7),oleanolic acid 3-O-β-D-glucopyranoside(8),oleanolic acid 3-O-6'-O-methyl-β-D-glucuronopyranoside(9),momordin Ib(10),chiisanoside(11),22α-hydroxy-chiisanoside(12),kalopanax saponins E(13);木脂素类化合物5个:分别为(-)-sesamin(14),simplexoside(15),(+)-syringaresinol-O-β-D-glucopyranosi-de(16),(-)-pinoresinol-4,4'-di-O-β-D-glucopyranoside(17),acanthoside D(18);香豆素类化合物4个:分别为scopoletin(19),scopolin methyl ether(20),isofraxidin(21),scopolin(22);黄酮类化合物2个:分别为quercetin(23),hyperin(24):单萜类化合物2个:为别为(3Z,6E)-3,7-dimethylocta-3,6-diene-1,2,8-triol(27),(E)-7-methyl-3-methyleneoct-6-ene-1,2,8-triol(28);酚酸类化合物11个:分别为niduloic acid(4),protocatechuic acid(25),protocatechuic acid methyl ester(26),tyrosol(29),p-hydrocoumaric acid(30),protocatechuic aldehyde(31),caffeic acid(32),4-(3,4-dihydroxyphenyl)-2-butanone(33),gallic acid(34),4-hydroxy-benzoic acid(35),pyrocatechol(36);糖类化合物2个:分别为蔗糖(37)和果糖(38);甾体类化合物2个:分别为胡萝卜苷(39)和β-谷甾醇(40)。其中化合物1、2、27、28为新化合物:化合物3、4为新天然产物;化合物15,17,19,20,22,26,33为首次从五加科植物中分离得到;化合物9,23,30为首次从五加属中分离得到;化合物5,7,8,10,13,29,35,36为首次从该植物中分离得到。
采用Born比浊法测定了3个三萜类化合物的体外抗血小板凝集活性。以DMSO为空白对照,以Aspirin为阳性对照,考察了3个三萜类化合物抗ADP诱导的体外血小板凝集活性,结果表明,3个化合物均有明显的抗ADP诱导的血小板凝集活性,其抗血小板凝集的强度与Aspirin接近。采用同样的方法考察了无梗五加果70%乙醇提取物在大鼠体内抗血小板凝集作用。结果表明,大鼠连续给予无梗五加果70%乙醇提取物(125,250,500,1000 mg/kg)15天后,大鼠的富血小板血浆(PRP)具有显著的抗ADP诱导的血小板凝集活性,在本文研究的剂量范围内呈剂量依赖性关系。采用大鼠动-静脉旁路循环模型进行无梗五加果70%乙醇提取物体内抗血栓的作用研究。结果表明,大鼠连续给予无梗五加果70%乙醇提取物(125,250,500,1000 mg/kg)15天后,动-静脉旁路循环模型的血栓湿重均有显著的降低,且各剂量的血栓湿重之间也均有显著性差异(P<0.05),在本文研究的剂量范围内呈剂量依赖性关系。
采用UPLC-ESI-MS/MS法同时测定了无梗五加果中10种三萜类成分的含量。色谱柱为ACQUITY UPLC~(TM) BEH C_(18) column(1.7μm,100 mm×2.1 mm,i.d.);流动相为5mmol/L醋酸铵水溶液(A)-乙腈(B),梯度洗脱;流速为0.25 mL/min;采用负离子检测方式,MRM扫描模式。10个三萜类成分在相应的线性范围内均呈良好的线性关系。应用该方法测定了无梗五加不同成熟期的果实中10个成分的含量,结果表明不同成熟期的无梗五加果中,10个成分的含量变化趋势各不相同,齐墩果酸及其苷类成分随着果实的不断成熟,在果实中的含量均呈平缓的上升趋势;开环羽扇豆烷型三萜苷类成分chiisanoside随着无梗五加果实的成熟,其在果实中的含量呈明显的下降趋势,而其苷元chiisanogenin则表现出明显的上升趋势,这种趋势可能是由苷断裂糖链逐渐转化成其苷元chiisanogenin导致的。本文所建立的分析方法专属、准确、灵敏、高效,为无梗五加果药材的质量评价提供了新的方法。
建立了测定大鼠血浆中chiisanogenin的UPLC-ESI-MS/MS分析方法。采用液-液萃取法进行血浆样品预处理,色谱柱为ACQUITY UPLC~(TM) BEH C_(18) column(1.7μm,50min×2.1 mm,i.d.);流动相为5 mmol/L醋酸铵水溶液-乙腈(10:90,v/v),等度洗脱;采用负离子检测方式,MRM扫描模式。利用该法分别研究了大鼠灌胃给予高、中、低3个剂量的单体chiisanogenin和相当于低剂量chiisanogenin的无梗五加果70%乙醇提取物后的药物动力学行为。统计学检验结果表明,在所研究的剂量范围内,chiisanogenin在大鼠体内呈线性药物动力学特征。与给药单体chiisanogenin相比,给药无梗五加果70%乙醇提取物后的AUC_(0-t)降低(P<0.05);大鼠血浆中chiisanogenin的药-时曲线出现双吸收峰现象,这种现象可能是由无梗五加果中存在的chiisanogenin的糖苷类成分在大鼠体内发生降解后转化成被测组分引起的。无梗五加果中其他成分影响了chiisanogenin的药动学行为。
Acanthopanax sessiliflorus(Rupr.et Maxim) Seem,belongs to Acanthopanax genus of the family Araliaceae.It is a shrub distributes mainly in China,Korea and Japan.It has traditionally been used as a tonic and a sedative,as well as in the treatment of rheumatism and diabetes.The chemical constituents,activities,analytical methods of Acanthopanax sessiliflorus fruits and pharmacokinetics of chiisanogenin were investigated in this study.
The chemical constituents of 70%ethanol extract of Acanthopanax sessiliflorus fruits were isolated by using multiple column chromatographic techniques,and 40 compounds were obtained.The structures of 40 compounds were fully elucidated by chemical and spectroscopic methods(1D,2D-NMR,MS).The identified compounds include twelve triterpenes:3-O-[(α-L-arabinopyranosyl)(1→2)]-[β-D-glucuronopyranosyl-6-O-methyl ester]-olean-12-ene-28-olic acid(1),(1R,11α,22α) 1,4-epoxy-11,22-hydroxy-3, 4-secolupane-20(30)-ene-3,28-dioic acid(2),(1R,11α)1,4-epoxy-11-hydroxy-3, 4-secolupane-20(30)-ene-3,28-dioic acid(3),22α-hydroxychiisanogenin(5),chiisanogenin (6),oleanolic acid(7),oleanolic acid 3-O-β-D-glucopyranoside(8),oleanolic acid 3-O-6'-O-methyl-β-D-glucuronopyranoside(9),momordin Ib(10),chiisanoside(11), 22a-hydroxychiisanoside(12),kalopanax saponins E(13);five lignans:(-)-sesamin(14), simplexoside(15),(+)-syringaresinol-O-β-D-glucopyranoside(16),(-)-pinoresinol-4, 4'-di-O-β-D-glucopyranoside(17),acanthoside D(18);four coumarins:scopoletin(19), scopolin methyl ether(20),isofraxidin(21),scopolin(22);two flavonoids:quercetin(23), hyperin(24);two monoterpenes:(3Z,6E)-3,7-dimethylocta-3,6-die-ne-1,2,8-triol(27), (E)-7-methyl-3-methyleneoct-6-ene-1,2,8-triol(28);eleven phenolic compounds:niduloic acid(4),protocatechuic acid(25),protocatechuic acid methyl ester(26),tyrosol(29), p-hydrocoumaric acid(30),protocatechuic aldehyde(31),caffeic acid(32),4-(3, 4-dihydroxyphenyl)-2-butanone(33),gallic acid(34),4-hydroxy-benzoic acid(35), pyrocatechol(36);tow sugars:sucrose(37),fructose(38);two steroids:daucosterol(39),β-sitosterol(40).Among them,four(1,2,27 and 28) were identified as new compounds, compounds 3 and 4 were identified as novel natural compounds;compounds 15,17,19,22, 26 and 33 were isolated from the family of Araliaceae for the first time;compounds 9,23 and 30 were isolated from the Acanthopanax genus for the first time;compounds 5,7,8,10,13, 29,35 and 36 were isolated from this plant for the first time.
The inhibitory activity on rat platelet aggregation induced by ADP in vitro of the two new compounds and a new natural product was tested by Born-nephelometer which was compared with that of aspirin(ASA).The three compounds showed excellent antiplatelet aggregation activity,which was almost equally potent to ASA.Platelet aggregation induced by ADP and thrombus weight in an arteriovenous thrombosis model were tested after 15 days treatment with 125,250,500 and 1000 mg/kg extract of Acanthopanax sessiliflorus fruits orally in rats, compared with 27 mg/kg ASA.The extract of Acanthopanax sessiliflorus fruits dose-dependently inhibited ADP induced platelet aggregation in vivo.Compared to a control thrombus weight of 108.1±2.7 mg,thrombus weight was 91.4±3.5,76.6±6.5,61.0±6.5 and 46.2±3.9 mg after treatment for 15 d with 125,250,500 and 1000 mg/kg(P<0.05) extract of Acanthopanax sessiliflorus fruits,respectively.Meanwhile,the thrombus weight was 62.9±6.7 mg after the treatment with 27 mg/kg of ASA.A dose-dependent relationship of anti-thrombotic effect was observed for the extract of Acanthopanax sessiliflorus fruits.
A UPLC-ESI-MS/MS method was developed for simultaneous quantitative determination of ten triterpenes in Acanthopanax sessiliflorus fruits.The analysis was performed on an ACQUITY UPLC~(TM)BEH C_(18) column(1.7μm,100 mm×2.1 mm,i.d.) using gradient elution with the mobile phase consisting of 5 mmol/L ammonium acetate in water and acetonitrile. The flow rate was 0.25 mL/min.The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring(MRM) mode via electrospray ionization (ESI) source.The method provided good accuracy and good precision and has been successfully applied to quantitative determination of ten compounds in the fruits from different fruits maturation periods.The contents of those compounds in samples from different fruits maturation periods varied significantly.
Chiisanogenin is an active compound of Acanthopanax sessiliflorus fruits with various pharmacological effects such as anti-platelet aggregation and anti-inflammatory effects.A specific,simple and sensitive UPLC-ESI-MS/MS method was developed and validated for the pharmacokinetic study of chiisanogenin in rat plasma.Chiisanogenin,with paracetamol as the internal standard,was extracted from plasma samples by liquid-liquid extraction.The analysis was carried out on an ACQUITY UPLC~(TM)BEH C_(18) column(1.7μm,50 mm×2.1 mm,i.d.) with mobile phase of acetonitrile-water containing 5 mmol/L ammonium acetate(90:10,v/v). The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring(MRM) mode via electrospray ionization(ESI) source.This validated method was successfully applied to a pharmacokinetic study in rats after oral administrations of chiisanogenin and the extract of Acanthopanax sessiliflorus fruits.Chiisanogenin showed a linear pharmacokinetics in rats in the studied dose range.Compared with the same dose of chiisanogenin,the AUCo-t of extract of Acanthopanax sessiliflorus fruits was decreased.The pharmacokinetic characteristic of the double peak in the plasma concentration-time curve of chiisanogenin may be attributed to the in vivo transforming of chisanoside into chiisanogenin. It was indicated that pharmacokinetic characteristic of chiisanogenin was affected by other constituents in extract of Acanthopanax sessiliflorus fruits.
引文
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