基于代谢组学研究厚朴远志配伍醇提物对尿液代谢物的影响
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摘要
目的考察厚朴远志配伍对大鼠尿液代谢物的影响,探索其特征生物标志物并分析相关代谢通路,为关联探索厚朴缓解远志胃肠动力障碍的可能机制提供参考。方法 SD♂大鼠40只,随机分为对照组、厚朴3. 50 g·kg~(-1)组、远志1. 75 g·kg~(-1)组、配伍3. 5+1. 75 g·kg~(-1)组,连续灌胃3 d,收集大鼠末次给药24 h内的尿液,采用UPLC-Q-TOF-MS检测各组尿液的代谢物,借助Progenesis QI V2. 0、SIMCA-P14. 0、SPSS 20. 0、Metabo Analyst 3. 0等软件,分析各组尿液代谢标志物及其代谢通路。结果对照组与给药组的代谢物能够明显区分,并筛选出2-氨基苯甲酸、D-葡萄糖醛酸-6,3-内酯、3-甲氧基-4-羟基苯乙醛等16个特征代谢标志物,主要涉及酪氨酸代谢、色氨酸代谢,以及苯丙氨酸、酪氨酸、色氨酸生物合成等通路。结论厚朴可能通过调控酪氨酸代谢、色氨酸代谢、初级胆汁酸生物合成和维生素B_6代谢等代谢通路,缓解远志所致胃肠动力障碍。
Aim To study the effect of compatibility of Magnolia officinalis and Polygala tenuifolia on urine metabolites in rats,to explore its characteristic biomarkers and analyze the related metabolic pathways,and to provide references for exploring the possible mechanisms of Magnolia officinalis relieving gastrointestinal motility disorders induced by Polygala tenuifolia.Methods Forty male Sprague-Dawley rats were randomly divided into control group,Polygala tenuifolia1. 75 g · kg~(-1) group,Magnolia officinalis 3. 50 g ·kg~(-1) group, and the compatibility group( 3. 50 +1. 75) g · kg~(-1),continuously orally administered for three days. Urine was collected within 24 hours after the last administration and detected by UPLC-Q-TOFMS in each group. The characteristic biomarkers and corresponding metabolic pathways were analyzed or screened by Progenesis QI V2. 0, SIMCA-P 14. 0,SPSS 20. 0,MetaboAnalyst 3. 0 and other softwares.Results The metabolites in control group and drugadministered group could be clearly distinguished,and a total of 16 characteristic metabolites,2-Aminobenzoic acid, D-Glucurono-6, 3-lactone and Homovanillin,were screened out. The main related pathways included Tyrosine metabolism,tryptophan metabolism,vitamin B_6 metabolism and primary bile acid biosynthesis. Conclusions The mechanism of Magnolia officinalis relieving gastrointestinal motility disorders induced by Polygala tenuifolia might be related with Tyrosine metabolism,tryptophan metabolism,primary bile acid biosynthesis and vitamin B_6 metabolism.
Aim To study the effect of compatibility of Magnolia officinalis and Polygala tenuifolia on urine metabolites in rats,to explore its characteristic biomarkers and analyze the related metabolic pathways,and to provide references for exploring the possible mechanisms of Magnolia officinalis relieving gastrointestinal motility disorders induced by Polygala tenuifolia.Methods Forty male Sprague-Dawley rats were randomly divided into control group,Polygala tenuifolia1. 75 g · kg~(-1) group,Magnolia officinalis 3. 50 g ·kg~(-1) group, and the compatibility group( 3. 50 +1. 75) g · kg~(-1),continuously orally administered for three days. Urine was collected within 24 hours after the last administration and detected by UPLC-Q-TOFMS in each group. The characteristic biomarkers and corresponding metabolic pathways were analyzed or screened by Progenesis QI V2. 0, SIMCA-P 14. 0,SPSS 20. 0,MetaboAnalyst 3. 0 and other softwares.Results The metabolites in control group and drugadministered group could be clearly distinguished,and a total of 16 characteristic metabolites,2-Aminobenzoic acid, D-Glucurono-6, 3-lactone and Homovanillin,were screened out. The main related pathways included Tyrosine metabolism,tryptophan metabolism,vitamin B_6 metabolism and primary bile acid biosynthesis. Conclusions The mechanism of Magnolia officinalis relieving gastrointestinal motility disorders induced by Polygala tenuifolia might be related with Tyrosine metabolism,tryptophan metabolism,primary bile acid biosynthesis and vitamin B_6 metabolism.
引文
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[9]丁健华,傅传刚,赵荣华.五羟色胺在胃肠道功能性疾病中的研究现状[J].世界华人消化杂志,2005,(20):2405-8.[9]Ding J H,Fu C G,Zhao R H.Research status of serotonin in gastrointestinal functional diseases[J].World Chin J Digestol,2005,(20):2405-8.
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[11]Cezary C,Tomasz P,Grazyna K,et al.Secretion of melatonin and6-sulfatoxymelatonin urinary excretion in functional dyspepsia[J].World J Gastroenterol,2011,17(21):2646-51.
[12]张卫卫.半夏厚朴汤及厚朴主要成分促胃肠运动、抗焦虑和抗抑郁作用的研究[D].沈阳:中国医科大学,2004.[12]Zhang W W.Effect of Banxia-Houpo decoction,magnolol and honokiol on gastrointestinal movement,and their anxiolytic and antidepressant effects[D].Shenyang:China Medical University,2004.
[13]Armstrong D N,Krenz H K,Modlin I M,et al.Bile salt inhibition of motility in the isolated perfused rabbit terminal ileum[J].Gut,1993,34(4):483-8.
[14]Camilleri M,Murphy R,Chadwick V S.Dose-related effects of chenode-oxycholic acid in the rabbit colon[J].Dig Dis Sci,1980,25:433-8.
[15]吐热娜依,汪忠诚.维生素B6对减轻阿奇霉素胃肠道不良反应的临床随机对照研究[J].中国实用医药,2006,(3):64-5.[15]Tu R N Y,Wang Z C.Clinical control study that vitamin B6alleviate abserve reaction of gasreoin testing tract that azitromycin inititate[J].China Practical Med,2006,(3):64-5.
[2]李达.远志与厚朴配伍前后化学成分对比及解毒机理初步研究[D].成都:成都中医药大学,2009.[2]Li D.Preliminary study on chemical composition comparison and detoxification mechanism between Polygalae and Magnolia before and after compatibility[D].Chengdu:Chengdu University of Traditional Chinese Medicine,2009.
[3]江娟,王建,李达,等.远志与厚朴不同煎煮时间及不同配比对小鼠胃肠运动的影响[J].西安交通大学学报(医学版),2009,30(3):380-2.[3]Jiang J,Wang J,Li D,et al.Effects of radix Polygalae and Magnolia of different decoction time and compatibility proportion on mouse gastrointestinal motility[J].J Xi'an Jiaotong Univ(Med Sci),2009,30(3):380-2.
[4]牟菲,段佳林,边海旭,等.降香水提物和挥发油对心肌缺血/再灌注损伤大鼠预防作用的代谢组学研究[J].中国药理学通报,2016,32(10):1377-82.[4]Mu F,Duan J L,Bian H X,et al.Metabolomic study on preventive effect of aqueous extract and volatile oil of Dalbergia Odorifera on myocardial ischemia/reperfusion injury in rats[J].Chin Pharmacol Bull,2016,32(10):1377-82.
[5]Manna S K,Patterson A D,Yang Q,et al.UPLC-MS-based urine metabolomics reveals indole-3-lactic acid and phenyllactic acid as conserved biomarkers for alcohol-induced liver disease in the Ppara-null mouse model[J].J Proteome Res,2011,10(9):4120-33.
[6]黄立华,王建,吴明权,等.远志、厚朴配伍对其活性成分在大鼠肠段吸收的影响[J].中成药,2015,37(4):739-45.[6]Huang L H,Wang J,Wu M Q,et al.Active elements from Yuanzhi and Houpo,and their intestinal absorption due to the combined use[J].Tradit Chin Med Patent Prescription,2015,37(4):739-45.
[7]Eisenhofer G,Aneman A,Friberg P,et al.Substantial production of dopamine in the human gastrointestinal tract[J].J Clin Endocrinol Metab,1997,82(11):3864-71.
[8]Tachikawa E,Takahashi M,Kashimoto T.Effects of extract and ingredients isolated from Magnolia obovata thunberg on catecholamine secretion from bovine adrenal chromaffin cells[J].Biochem Pharmacol,2000,60(3):433-40.
[9]丁健华,傅传刚,赵荣华.五羟色胺在胃肠道功能性疾病中的研究现状[J].世界华人消化杂志,2005,(20):2405-8.[9]Ding J H,Fu C G,Zhao R H.Research status of serotonin in gastrointestinal functional diseases[J].World Chin J Digestol,2005,(20):2405-8.
[10]Aydin M,Canpolat S,Kuloglu T,et al.Effects of pinealectomy and exogenous melatonin on ghrelin and peptide YY in gastrointestinal system and neuropeptide Y in hypothalamic arcuate nucleus:immunohistochemical studies in male rats[J].Regul Pept,2008,146(1-3):197-203.
[11]Cezary C,Tomasz P,Grazyna K,et al.Secretion of melatonin and6-sulfatoxymelatonin urinary excretion in functional dyspepsia[J].World J Gastroenterol,2011,17(21):2646-51.
[12]张卫卫.半夏厚朴汤及厚朴主要成分促胃肠运动、抗焦虑和抗抑郁作用的研究[D].沈阳:中国医科大学,2004.[12]Zhang W W.Effect of Banxia-Houpo decoction,magnolol and honokiol on gastrointestinal movement,and their anxiolytic and antidepressant effects[D].Shenyang:China Medical University,2004.
[13]Armstrong D N,Krenz H K,Modlin I M,et al.Bile salt inhibition of motility in the isolated perfused rabbit terminal ileum[J].Gut,1993,34(4):483-8.
[14]Camilleri M,Murphy R,Chadwick V S.Dose-related effects of chenode-oxycholic acid in the rabbit colon[J].Dig Dis Sci,1980,25:433-8.
[15]吐热娜依,汪忠诚.维生素B6对减轻阿奇霉素胃肠道不良反应的临床随机对照研究[J].中国实用医药,2006,(3):64-5.[15]Tu R N Y,Wang Z C.Clinical control study that vitamin B6alleviate abserve reaction of gasreoin testing tract that azitromycin inititate[J].China Practical Med,2006,(3):64-5.