Pharmacokinetics and Disposition of Circulating Iridoids and Organic Acids in Rats Intravenously Receiving ReDuNing Injection
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- 英文论文题名：Pharmacokinetics and Disposition of Circulating Iridoids and Organic Acids in Rats Intravenously Receiving ReDuNing Injection
- 论文作者：Chen Cheng ; Feifei Du ; Ke Yu ; Fang Xu ; Fengqing Wang ; Li Li ; Olajide E.Olaleye ; Junling Yang ; Feng Chen ; Chenchun Zhong ; Qiongwei Liu ; Jing Li ; Zhenzhong Wang ; Chuan Li ; Wei Xiao
- 英文论文作者：Chen Cheng ; Feifei Du ; Ke Yu ; Fang Xu ; Fengqing Wang ; Li Li ; Olajide E.Olaleye ; Junling Yang ; Feng Chen ; Chenchun Zhong ; Qiongwei Liu ; Jing Li ; Zhenzhong Wang ; Chuan Li ; Wei Xiao ; State Key Laboratory of Drug Research ; Shanghai Institute of Materia Medica ; Chinese Academy of Sciences ; Jiangsu Kanion Pharmaceutical Corporation
- 年：2016
- 作者机构：State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences;Jiangsu Kanion Pharmaceutical Corporation;
- 会议召开时间：2016-09-27
- 会议录名称：中国药学会第十三届青年药学科研成果交流会论文集
- 语种：英文
- 分类号：R285.5
- 学会代码：YYWS
- 会议名称：中国药学会第十三届青年药学科研成果交流会
- 会议地点：中国江西南昌
- 主办单位：中国药学会
- 学会名称：中国药学会
- 页数：13
- 文件大小：1705k
- 原文格式：O
- 会议级别：全国
摘要
ReDuNing injection,prepared from a combination of Gardenia Jasminoides fruits,Lonicera japonica flower buds,and Artemisia annua aerial part,is extensively used for treatment of viral upper respiratory tract infection in China.Iridoids,organic acids,and flavonoids are probably important for the herbal injection because of their reported pharmacological properties.This study was designed to characterize pharmacokinetics and disposition of major circulating herbal compounds in rats intravenously receiving the injection.ReDuNing injection was found to contain 19 iridoids(content levels,0.01-27.93 mM),16 organic acids(0.04-19.06 mM),and 11 flavonoids(<0.08 mM).After dosing the injection,the iridoids geniposide,secologanic acid,secoxyloganin,genipin-l-β-gentiobioside,geniposidic acid,sweroside,and shanzhiside and the organic acids chlorogenic acid,quinic acid,cryptochlorogenic acid,and neochlorogenic acid were found to be the major circulating compounds with mean elimination half-lives of 0.2-0.9 hour,whereas other plasma compounds were at low exposure levels.These major circulating compounds exhibited small apparent volumes of distribution(0.03-0.34 1/kg).Most of the iridoids were eliminated predominantly via renal excretion of the unchanged compounds,whereas the organic acids were eliminated via methylation and sulfation and excreted into urine as the unchanged and metabolized compounds.The methylated metabolites also underwent subsequent conjugations before hepatobiliary and renal excretion.In vitro data suggested that the preceding metabolism of the organic acids in rats also occurred in humans.The current pharmacokinetic research could serve as a crucial step in identifying the chemical basis responsible for the therapeutic action of ReDuNing injection.
ReDuNing injection,prepared from a combination of Gardenia Jasminoides fruits,Lonicera japonica flower buds,and Artemisia annua aerial part,is extensively used for treatment of viral upper respiratory tract infection in China.Iridoids,organic acids,and flavonoids are probably important for the herbal injection because of their reported pharmacological properties.This study was designed to characterize pharmacokinetics and disposition of major circulating herbal compounds in rats intravenously receiving the injection.ReDuNing injection was found to contain 19 iridoids(content levels,0.01-27.93 mM),16 organic acids(0.04-19.06 mM),and 11 flavonoids(<0.08 mM).After dosing the injection,the iridoids geniposide,secologanic acid,secoxyloganin,genipin-l-β-gentiobioside,geniposidic acid,sweroside,and shanzhiside and the organic acids chlorogenic acid,quinic acid,cryptochlorogenic acid,and neochlorogenic acid were found to be the major circulating compounds with mean elimination half-lives of 0.2-0.9 hour,whereas other plasma compounds were at low exposure levels.These major circulating compounds exhibited small apparent volumes of distribution(0.03-0.34 1/kg).Most of the iridoids were eliminated predominantly via renal excretion of the unchanged compounds,whereas the organic acids were eliminated via methylation and sulfation and excreted into urine as the unchanged and metabolized compounds.The methylated metabolites also underwent subsequent conjugations before hepatobiliary and renal excretion.In vitro data suggested that the preceding metabolism of the organic acids in rats also occurred in humans.The current pharmacokinetic research could serve as a crucial step in identifying the chemical basis responsible for the therapeutic action of ReDuNing injection.
ReDuNing injection,prepared from a combination of Gardenia Jasminoides fruits,Lonicera japonica flower buds,and Artemisia annua aerial part,is extensively used for treatment of viral upper respiratory tract infection in China.Iridoids,organic acids,and flavonoids are probably important for the herbal injection because of their reported pharmacological properties.This study was designed to characterize pharmacokinetics and disposition of major circulating herbal compounds in rats intravenously receiving the injection.ReDuNing injection was found to contain 19 iridoids(content levels,0.01-27.93 mM),16 organic acids(0.04-19.06 mM),and 11 flavonoids(<0.08 mM).After dosing the injection,the iridoids geniposide,secologanic acid,secoxyloganin,genipin-l-β-gentiobioside,geniposidic acid,sweroside,and shanzhiside and the organic acids chlorogenic acid,quinic acid,cryptochlorogenic acid,and neochlorogenic acid were found to be the major circulating compounds with mean elimination half-lives of 0.2-0.9 hour,whereas other plasma compounds were at low exposure levels.These major circulating compounds exhibited small apparent volumes of distribution(0.03-0.34 1/kg).Most of the iridoids were eliminated predominantly via renal excretion of the unchanged compounds,whereas the organic acids were eliminated via methylation and sulfation and excreted into urine as the unchanged and metabolized compounds.The methylated metabolites also underwent subsequent conjugations before hepatobiliary and renal excretion.In vitro data suggested that the preceding metabolism of the organic acids in rats also occurred in humans.The current pharmacokinetic research could serve as a crucial step in identifying the chemical basis responsible for the therapeutic action of ReDuNing injection.
引文
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[2].Dawidowicz AL and Typek R(2014)Transformation of 5-O-caffeoylquinic acid in blueberries during high-temperature processing.J Agric Food Chem 62:10889-10895.
[3].Guo B,Li C,Wang G-J,and Chen L-S(2006)Rapid and direct measurement of free concentrations of highly protein-bound fluoxetine and its metabolite norfluoxetine in plasma.Rapid Commun Mass Spectrom 20:39-47.
[4].Li H-B.Yu Y,Wang Z-Z,Geng J-L,Dai Y.Xiao W,and Yao X-S(2015a)Chemical profiling of ReDuNing injection by ultra-performance liquid chromatography coupled with electrospray ionization tandem quadrupole time-of-flight mass spectrometry through the screening of diagnostic ions in MS~E mode.PLoS One 10:e0121031.
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[6].Li X-H,Zhang X,Ding J-B,Xu Y,Wei D,Tian Y-M,Chen W,Huang J-H,Wen T,and Li S-J(2014)Comparison between Chinese herbal medicines and conventional therapy in the treatment of severe hand,foot,and mouth disease:a randomized controlled trial.Evid Based Complement Alternat Med 2014:140764.
[7].Liu H,Chen Y-F,Li F,and Zhang H-Y(2013)Fructus Gardenia(Gardenia jasminoides J.Ellis)phytochemistry.pharmacology of cardiovascular,and safety with the perspective of new drugs development.J Asian Nat Prod Res 15:94-110.
[8].Liu H-F,Yang J-L,Du F-F,Gao X-M,Ma X-T,Huang Y-H,Xu F,Niu W,Wang F-Q,Mao Y et al.(2009)Absorption and disposition of ginsenosides after oral administration of Panax notoginseng extract to rats.Drug Metab Dispos 37:2290-2298.
[9].Ni T-Q,Hu S-Y,Si D-Y,Wei G-L,and Xia Y-Y(2015)Experimental study on pharmacokinetics of ReDuNing injection in human body.Chinese tradit herb drugs 46:2270-2274.
[10].Reagan-Shaw S,Nihal M,and Ahmad N(2008)Dose translation from animal to human studies revisited.FASEB J 22:659-661.
[11].Shang X-F,Pan H,Li M-X,Miao X-L,and Ding H(2011)Lonicera japonica Thunb.:ethnopharmacology,phytochemistry and pharmacology of an important traditional Chinese medicine.J Ethnopharmacol 138:1-21.
[12].Toutain PL and Bousquet-Melou A(2004)Plasma clearance.J Vet Pharmacol Ther 27:427-439.
[13].Wang Y,Wen J,Zheng W,Zhao L,Fu X,Wang Z,Xiong Z,Li F,and Xiao W(2015)Simultaneous determination of neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid and geniposide in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study after administration of ReDuNing injection.Biomed Chromatogr 29:68-74.
[14].Xu H-M,Wang Y,and Liu N-F(2009)Safety of an injection with a mixture of extracts from Herba Artemisiae annuae,Fructus Gardeniae and Flos Lonicerae.Pharm World Sci 31:458-463.
[2].Dawidowicz AL and Typek R(2014)Transformation of 5-O-caffeoylquinic acid in blueberries during high-temperature processing.J Agric Food Chem 62:10889-10895.
[3].Guo B,Li C,Wang G-J,and Chen L-S(2006)Rapid and direct measurement of free concentrations of highly protein-bound fluoxetine and its metabolite norfluoxetine in plasma.Rapid Commun Mass Spectrom 20:39-47.
[4].Li H-B.Yu Y,Wang Z-Z,Geng J-L,Dai Y.Xiao W,and Yao X-S(2015a)Chemical profiling of ReDuNing injection by ultra-performance liquid chromatography coupled with electrospray ionization tandem quadrupole time-of-flight mass spectrometry through the screening of diagnostic ions in MS~E mode.PLoS One 10:e0121031.
[5].Li M-J,Wang F-Q,Huang Y-H,Du F-F,Zhong C-C,Olaleye OE,Jia W-W,Li Y-F,Xu F,and Dong J-J et al.(2015b)Systemic exposure to and disposition of catechols,derived from Salvia miltiorrhiza roots(Danshen),after intravenous dosing DanHong injection in human subjects,rats,and dogs.Drug Metab Dispos 43:679-690.
[6].Li X-H,Zhang X,Ding J-B,Xu Y,Wei D,Tian Y-M,Chen W,Huang J-H,Wen T,and Li S-J(2014)Comparison between Chinese herbal medicines and conventional therapy in the treatment of severe hand,foot,and mouth disease:a randomized controlled trial.Evid Based Complement Alternat Med 2014:140764.
[7].Liu H,Chen Y-F,Li F,and Zhang H-Y(2013)Fructus Gardenia(Gardenia jasminoides J.Ellis)phytochemistry.pharmacology of cardiovascular,and safety with the perspective of new drugs development.J Asian Nat Prod Res 15:94-110.
[8].Liu H-F,Yang J-L,Du F-F,Gao X-M,Ma X-T,Huang Y-H,Xu F,Niu W,Wang F-Q,Mao Y et al.(2009)Absorption and disposition of ginsenosides after oral administration of Panax notoginseng extract to rats.Drug Metab Dispos 37:2290-2298.
[9].Ni T-Q,Hu S-Y,Si D-Y,Wei G-L,and Xia Y-Y(2015)Experimental study on pharmacokinetics of ReDuNing injection in human body.Chinese tradit herb drugs 46:2270-2274.
[10].Reagan-Shaw S,Nihal M,and Ahmad N(2008)Dose translation from animal to human studies revisited.FASEB J 22:659-661.
[11].Shang X-F,Pan H,Li M-X,Miao X-L,and Ding H(2011)Lonicera japonica Thunb.:ethnopharmacology,phytochemistry and pharmacology of an important traditional Chinese medicine.J Ethnopharmacol 138:1-21.
[12].Toutain PL and Bousquet-Melou A(2004)Plasma clearance.J Vet Pharmacol Ther 27:427-439.
[13].Wang Y,Wen J,Zheng W,Zhao L,Fu X,Wang Z,Xiong Z,Li F,and Xiao W(2015)Simultaneous determination of neochlorogenic acid,chlorogenic acid,cryptochlorogenic acid and geniposide in rat plasma by UPLC-MS/MS and its application to a pharmacokinetic study after administration of ReDuNing injection.Biomed Chromatogr 29:68-74.
[14].Xu H-M,Wang Y,and Liu N-F(2009)Safety of an injection with a mixture of extracts from Herba Artemisiae annuae,Fructus Gardeniae and Flos Lonicerae.Pharm World Sci 31:458-463.