基于在体肠灌流模型的四妙勇安汤活性成分拆方配伍研究
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摘要
采用大鼠在体单向肠灌流模型,以UPLC-MSn测定四妙勇安汤水提物中绿原酸、甘草苷、金丝桃苷、安格洛苷C和异绿原酸C 5种抗炎活性成分在不同拆方配伍组合及不同肠段中的含量,通过计算所得到的肠吸收参数为指标对上述成分在多种配伍组合中的肠吸收情况进行评价。结果显示,四妙勇安汤5种活性成分中,除甘草苷回肠吸收参数在单味甘草中最高,其余4种成分在回肠和十二指肠中的肠吸收参数均配伍组合时高。其中,绿原酸在全方配伍时回肠和十二指肠吸收参数均处于最高水平,异绿原酸C在全方及金银花-玄参-甘草3药配伍组合时吸收参数处于较高水平,而不同配伍组合中的金丝桃苷和安格洛苷C的肠吸收情况在回肠和十二指肠中截然相反。该研究通过考察四妙勇安汤中5种活性成分在不同拆方配伍组合的肠吸收情况,揭示了活性成分的吸收往往会因配伍组合方式及肠段的不同而有所差异。同时也表明了通过复方配伍,可明显促进活性成分的吸收,从生物学角度为四妙勇安汤配伍规律的研究奠定了一定的基础。
To study the compatibility rule of Simao Yongan Decoction,the rat single pass intestinal perfusion model in situ was used in this study. On the basis of early research,the five kinds of anti-inflammatory active ingredients,i.e. chlorogenic acid,liquiritin,hyperoside,angoroside C and isochlorogenic acid C in Simao Yongan Decoction were selected as research objects. The contents of the above five actives compounds with various compatibility combinations and in different intestinal segment perfusates were determined by using the method of ultra-performance liquid chromatography-mass spectrometry( UPLC-MSn). The kinetic parameters of intestinal absorption of the five anti-inflammatory active ingredients were calculated,which could be used to evaluate the intestinal absorption of each component in different combinations. The results showed that the absorption parameters of liquiritin in ileum were highest in Glycyrrhizae Radix et Rhizoma single herb,while the absorption parameters of other four components in ileum and duodenum were highest in the compatible combinations. Among them,the absorption parameters of chlorogenic acid in ileum and duodenum were highest in the whole prescription compatibility; ischlorogenic acid C showed higher absorption levels in the whole prescription and the herb compatibility of Lonicerae Japonicae Flos-Scrophulariae Radix-Glycyrrhizae Radix et Rhizoma. However,the absorption levels of hyperoside and angoroside C in different compatibilities were quite different in ileum and duodenum. In this study,the intestinal absorption of five anti-inflammatory active ingredients in Simiao Yongan Decoction with different compatibility combinations was investigated,revealing that the absorption of active ingredients varied with the different compatibility combinations and different intestinal segments. At the same time,the above research also indicated that the absorption of active ingredients could be obviously promoted by the compatibility of compound prescriptions,laying a foundation for the research on the compatibility rule of Simiao Yongan Detection from the biological point of view.
To study the compatibility rule of Simao Yongan Decoction,the rat single pass intestinal perfusion model in situ was used in this study. On the basis of early research,the five kinds of anti-inflammatory active ingredients,i.e. chlorogenic acid,liquiritin,hyperoside,angoroside C and isochlorogenic acid C in Simao Yongan Decoction were selected as research objects. The contents of the above five actives compounds with various compatibility combinations and in different intestinal segment perfusates were determined by using the method of ultra-performance liquid chromatography-mass spectrometry( UPLC-MSn). The kinetic parameters of intestinal absorption of the five anti-inflammatory active ingredients were calculated,which could be used to evaluate the intestinal absorption of each component in different combinations. The results showed that the absorption parameters of liquiritin in ileum were highest in Glycyrrhizae Radix et Rhizoma single herb,while the absorption parameters of other four components in ileum and duodenum were highest in the compatible combinations. Among them,the absorption parameters of chlorogenic acid in ileum and duodenum were highest in the whole prescription compatibility; ischlorogenic acid C showed higher absorption levels in the whole prescription and the herb compatibility of Lonicerae Japonicae Flos-Scrophulariae Radix-Glycyrrhizae Radix et Rhizoma. However,the absorption levels of hyperoside and angoroside C in different compatibilities were quite different in ileum and duodenum. In this study,the intestinal absorption of five anti-inflammatory active ingredients in Simiao Yongan Decoction with different compatibility combinations was investigated,revealing that the absorption of active ingredients varied with the different compatibility combinations and different intestinal segments. At the same time,the above research also indicated that the absorption of active ingredients could be obviously promoted by the compatibility of compound prescriptions,laying a foundation for the research on the compatibility rule of Simiao Yongan Detection from the biological point of view.
引文
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[9]张翠英,任伟光.基于经典丹参药对“丹参-冰片”、“丹参-红花”的药动学研究探讨中药配伍增效的药动学研究策略[J].中国中药杂志,2017,42(12):2413.
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[13]胡少伟,姜艳艳,高尧春,等.四妙勇安汤中甘草苷、金丝桃苷和木犀草苷提取率的拆方分析[J].北京中医药大学学报,2016,39(7):590.
[14]董世奇,樊慧蓉,李全胜,等.甘草苷在大鼠体内的代谢途径研究[J].中草药,2014,45(17):2499.
[15] Zhang L Q,Huang Y D,Yang X W. Intestinal permeability of liquiritin and isoliquiritin in the Caco-2 cell monolayer model[J]. J Chin Pharm Sci,2010,19(6):451.
[16]刘姗姗,李凌军,徐继航.四妙勇安汤中绿原酸、甘草苷、阿魏酸在大鼠离体小肠的吸收动力学研究[J].中南药学,2015,13(4):369.
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[18]尹秀文,侯成波,陈江鹏,等.采用在体单向肠灌流模型研究荷叶多成分整体的肠渗透性[J].中国中药杂志,2017,42(8):1525.
[19]王帅,李清清,王帆,等.葛根素药物纳米晶自稳定pickering乳的大鼠肠吸收特性研究[J].中国中药杂志,2018,43(10):2162.
[20]吴干斌,褚延乐.大鼠在体单向肠灌流模型研究冬凌草乙素的吸收动力学[J].中国中药杂志,2018,43(15):3192.
[21]韩珂,谢志红,叶丽卡.在体单向肠灌流模型研究槲皮素的大鼠肠吸收特性[J].今日药学,2014,24(3):149.
[22]何帅,蔺明煊,姜亦南,等.中药成分肠吸收模型研究进展与思考[J].中医药学报,2018,46(3):121.
[23]吴林霖,李梅,巩仔鹏,等.基于大鼠离体外翻肠囊模型考察杜仲提取物在正常和自发性高血压状态下的肠吸收特性差异[J].中国实验方剂学杂志,2018,24(9):15.
[2]刘鹏,张恩惠,张薇,等.四妙勇安汤水煎液化学成分研究[J].中草药,2018,49(14):3232.
[3]宋亚玲,王红梅,倪付勇,等.金银花中酚酸类成分及其抗炎活性研究[J].中草药,2015,46(4):490.
[4]杨志军,邓毅,曼琼,等.甘草内生菌代谢物的抗炎作用[J].中国现代应用药学,2018,35(5):633.
[5] Díaz A M,Abad M J,Fernández L,et al. Phenylpropanoid glycosides from Scrophularia scorodonia:in vitro anti-inflammatory activity[J]. Life Sci,2004,74(20):2515.
[6]张刘强,李医明.近10年玄参属植物化学成分和药理作用研究进展[J].中草药,2011,42(11):2360.
[7]刘文君,程宁波,孟兆青,等.药对研究——三七、白及药对配伍前后对三七皂苷成分含量的影响[J].中国中药杂志,2016,41(5):887.
[8]刘莹,仲青香,邱辉辉,等.基于肝毒性的雷公藤中药复方配伍减毒的研究进展[J].中国中药杂志,2017,42(16):3044.
[9]张翠英,任伟光.基于经典丹参药对“丹参-冰片”、“丹参-红花”的药动学研究探讨中药配伍增效的药动学研究策略[J].中国中药杂志,2017,42(12):2413.
[10]迟森森,王卫华,刘斌.四妙勇安汤水提物大鼠吸收入血成分研究[J].北京中医药大学学报,2016,39(11):933.
[11]柏希慧,刘诗雨,王晶,等.单向灌流法评价复方龙脉宁汤剂配伍对葛根素肠吸收的影响[J].中国中药杂志,2017,42(1):157.
[12]季新宇,王翀,刘斌.四妙勇安汤当药苷、马钱苷提取率的拆方分析[J].中国实验方剂学杂志,2014,20(17):102.
[13]胡少伟,姜艳艳,高尧春,等.四妙勇安汤中甘草苷、金丝桃苷和木犀草苷提取率的拆方分析[J].北京中医药大学学报,2016,39(7):590.
[14]董世奇,樊慧蓉,李全胜,等.甘草苷在大鼠体内的代谢途径研究[J].中草药,2014,45(17):2499.
[15] Zhang L Q,Huang Y D,Yang X W. Intestinal permeability of liquiritin and isoliquiritin in the Caco-2 cell monolayer model[J]. J Chin Pharm Sci,2010,19(6):451.
[16]刘姗姗,李凌军,徐继航.四妙勇安汤中绿原酸、甘草苷、阿魏酸在大鼠离体小肠的吸收动力学研究[J].中南药学,2015,13(4):369.
[17]吕鹏.甘草苷及其苷元的透膜转运特征及初步药代动力学评价[D].北京:中国人民解放军军事医学科学院,2008.
[18]尹秀文,侯成波,陈江鹏,等.采用在体单向肠灌流模型研究荷叶多成分整体的肠渗透性[J].中国中药杂志,2017,42(8):1525.
[19]王帅,李清清,王帆,等.葛根素药物纳米晶自稳定pickering乳的大鼠肠吸收特性研究[J].中国中药杂志,2018,43(10):2162.
[20]吴干斌,褚延乐.大鼠在体单向肠灌流模型研究冬凌草乙素的吸收动力学[J].中国中药杂志,2018,43(15):3192.
[21]韩珂,谢志红,叶丽卡.在体单向肠灌流模型研究槲皮素的大鼠肠吸收特性[J].今日药学,2014,24(3):149.
[22]何帅,蔺明煊,姜亦南,等.中药成分肠吸收模型研究进展与思考[J].中医药学报,2018,46(3):121.
[23]吴林霖,李梅,巩仔鹏,等.基于大鼠离体外翻肠囊模型考察杜仲提取物在正常和自发性高血压状态下的肠吸收特性差异[J].中国实验方剂学杂志,2018,24(9):15.