药学学报, 2020, 55(2): 330-334
引用本文:
陈红珊, 杨玉琴, 张昊, 王鹏龙, 雷海民. 基于分子热力学特征探讨中药黄芩的归经特性[J]. 药学学报, 2020, 55(2): 330-334.
CHEN Hong-shan, YANG Yu-qin, ZHANG Hao, WANG Peng-long, LEI Hai-min. Meridian tropism of Scutellaria baicalensis based on molecular thermodynamic characteristics[J]. Acta Pharmaceutica Sinica, 2020, 55(2): 330-334.

基于分子热力学特征探讨中药黄芩的归经特性
陈红珊, 杨玉琴, 张昊, 王鹏龙, 雷海民
北京中医药大学中药学院, 北京市中药基础与新药研究重点实验室, 北京102488
摘要:
药性是中药的“身份证”,而归经又是破解中药药性理论的密钥。本实验基于分子热力学,从微观的能量释放与吸收角度研究中药与离体器官相互作用的效应变化,以期构建表征归经理论的新思路。以黄芩为例,应用等温滴定量热技术(isothermal titration calorimetry,ITC)分别测定黄芩与其主要活性成分黄芩苷与离体组织脑、心、肺、脾、肾的相互作用过程中能量的变化,比较结合常数(association constant,Ka)、解离常数(disassociationconstant,Kd)、结合计量比(stoichiometry ratio,n)、焓变(enthalpy change,ΔH)、熵变(entropy change,ΔS)和吉布斯自由能(Gibbs free energy,ΔG)等热力学参数。结果发现,黄芩与肺的作用强度明显高于其他脏器,此结论与古籍黄芩归经一致;此外,主要活性成分黄芩苷也显现与黄芩一致的作用规律。热力学参数分析结果表明该作用为熵和焓共同驱动的弱键诱导的自发化学结合反应。比旋度测量结果进一步证明黄芩苷与肺存在相互作用,并与ITC滴定结果相吻合,表明ITC能用于表征中药归经理论。动物实验获得北京中医药大学实验动物伦理委员会批准。因此,基于ITC建立的以中药水煎液与其活性成分分别与离体组织相互作用的能量变化大小表征中药归经的方法是科学、可行的,此实验为探讨中药及其功效成分归经理论提供了新思路。
关键词:    黄芩      黄芩苷      归经      等温滴定量热技术      分子热力学     
Meridian tropism of Scutellaria baicalensis based on molecular thermodynamic characteristics
CHEN Hong-shan, YANG Yu-qin, ZHANG Hao, WANG Peng-long, LEI Hai-min
Key Laboratory of Traditional Chinese Medicine and New Drug Research, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China
Abstract:
The property of medicine is the "identity card" of traditional Chinese medicine (TCM), and the key to crack the theory of property of TCM. Based on molecular thermodynamics, the effects of interaction between TCM and organs in vitro were studied from the perspective of micro-energy release and absorption in order to construct a new idea of characterizing meridian theory. Scutellaria baicalensis, for example, application of isothermal titration calorimetry (ITC) were used to determine the energy changes during the interaction of Scutellaria baicalensis and its main active ingredient baicalin with brain, heart, lung, spleen and kidney in vitro, comparison including the association constant (Ka) and disassociation constant (Kd), combined with thermodynamic parameters, such as stoichiometry ratio (n), enthalpy change (ΔH), entropy change (ΔS), Gibbs free energy (ΔG), it is found that the interaction intensity between Scutellaria baicalensis and lung is significantly stronger than that of other organs, which is consistent with the theory of the return of Scutellaria baicalensis in ancient books. In addition, baicalin, the main active ingredient, showed the same action pattern as Scutellaria baicalensis. The thermodynamic parameters analysis showed that the action was a weak bond-induced spontaneous chemical binding reaction driven by both entropy and enthalpy. The results of specific curl measurement further proved the interaction between baicalin and lung, and were consistent with the results of ITC titration, indicating that ITC could be used to characterize the meridian tropism of TCM. Therefore, based on ITC, it is scientific and feasible to characterize the meridian of TCM by the energy change of the interaction between the decoction of TCM and its active components and the in vitro tissues respectively. This experiment provides a new idea for the discussion of meridian of TCM.
Key words:    Scutellaria baicalensis    baicalin    meridian tropism    isothermal titration calorimetry    molecular thermodynamics   
收稿日期: 2019-07-22
DOI: 10.16438/j.0513-4870.2019-0588
基金项目: 国家自然科学基金资助项目(81603256);中央高校基金科研业务项目(岐黄团队2019-JYB-TD005);杰出青年基金资助项目(BUCM-2019-JCRC002,BUCM-2018-2020);中华中医药学会青年人才托举工程项目(CACM-2018-QNRC2-B08).
通讯作者: 王鹏龙,Tel:86-10-53912100,E-mail:wpl581@126.com;雷海民,E-mail:hm_lei@126.com
Email: wpl581@126.com;hm_lei@126.com
相关功能
PDF(506KB) Free
打印本文
0
作者相关文章
陈红珊  在本刊中的所有文章
杨玉琴  在本刊中的所有文章
张昊  在本刊中的所有文章
王鹏龙  在本刊中的所有文章
雷海民  在本刊中的所有文章

参考文献:
[1] Wang J. Genetic Research on the Theory of Meridian Tropism of Traditional Chinese Medicine (中药归经理论的发生学研究)[D]. Shenyang:Liaoning University of Traditional Chinese Medicine, 2012.
[2] Zang WH, Cai YM. Textual research of terminology ‘Channel Tropism’[J]. Chin J Tradit Chin Med Pharm (中华中医药杂志), 2017, 32:4067-4069.
[3] Li LL, Wang J, Cui Y, et al. Antirheumatic substance and meridian tropism of Loranthus parasiticus based on "syndrome-efficacy-analysis of biological samples"[J]. China J Chin Mater Med (中国中药杂志), 2016, 41:1933-1939.
[4] Jiang M, Sun XJ, Fu W, et al. Comparative study on the content of microelement Cu, Zn and Mn in eye tissue of rats treated by Rhizoma Corydalis before and after vinegar processing[J]. Chin Pharm (中国药师), 2015, 18:220-222.
[5] Zhong BX, Liu WZ, Qin AN, et al. Reviews the research on Chinese meridian theory by the method of cyclic nucleotide detection[J]. J Minzu Univ China (Nat Sci Ed) (中央民族大学学报(自然科学版)), 2011, 20:61-64.
[6] Teng J, Liang YH, Li Y, et al. Study on meridian tropism of Evodiae Fructus based on receptors of its secondary metabolites using system biological method[J]. Chin Tradit Herb Drugs (中草药), 2018, 49:1841-1846.
[7] Deng KW, He FY. Status of reaching meridian research for Chinese matria medica and to raise "point-medicine" method[J]. China J Chin Mater Med (中国中药杂志), 2013, 38:1643-1648.
[8] He FY, Zhou YQ, Deng KW, et al. Special impact of supramolecular chemistry on Chinese medicine theories[J]. China J Chin Mater Med (中国中药杂志), 2014, 39:1534-1543.
[9] He FY, Deng FY, Yang YT, et al. Study on meridian tropism of medicinal property theory for Chinese medicines by supramolecular chemistry (Ⅰ)[J]. China J Chin Mater Med (中国中药杂志), 2015, 40:1624-1629.
[10] Zhou J, Liu H, Liu WL, et al. Developing an integrated model of toxicity and efficacy of Chinese medicine based on supramolecular "imprinting template" analysis[J]. Acta Pharm Sin (药学学报), 2018, 53:1808-1816.
[11] Li T, Zhang H, Tian XH, et al. New qualities control strategy of Scutellaria baicalensis by isothermal titration calorimetry[J]. China J Chin Mater Med (中国中药杂志), 2017, 42:3969-3973.
[12] Li T, Wang H, Zhang H, et al. Formation mechanism of precipitation in Huanglian Jiedu Decoction based on molecular thermodynamic characteristics[J]. Chin Tradit Herb Drugs (中草药), 2017, 48:3505-3510.
[13] Thanassoulas A, Nounesis G. Isothermal titration calorimetry:a powerful tool for the characterization of molecular interactions//Thermodynamics and Biophysics of Biomedical Nanosystems[M]. Singapore:Springer, 2019:63-103.
[14] Leavitt S, Freire E. Direct measurement of protein binding energetics by isothermal titration calorimetry[J]. Curr Opin Struct Biol, 2001, 11:560-566.
[15] Yan D, Chen LH, Feng X, et al. Characterization of interaction in Qingkailing injection with clinic administration based on isothermal titration calorimetry[J]. Chin Tradit Herb Drugs (中草药), 2012, 43:2217-2221.
[16] Liu HY, Ma LN, Zhang P, et al. Compatibility research of Yiqi Fumai injection with clinical combination based on isothermal titration calorimetry[J]. China J Chin Mater Med (中国中药杂志), 2015, 40:889-893.
[17] Jin P, Li J, Liu CZ. Pharmacokinetics and tissue distribution of baicalin magnesium salt freeze-dried powder for injection in rats[J]. Chin J Exp Tradit Med Formul (中国实验方剂学杂志), 2019, 25:102-108.
[18] Gao XS. Several prerequisites for modern studies of meridian theory[J]. Chin J Basic Med Tradit Chin Med (中国中医基础医学杂志), 2003, 9:9-10, 12.
相关文献:
1.刘雪松, 张丝雨, 赵曼茜, 王钧, 李页瑞, 代军, 滕传震, 柯潇, 陈勇, 吴永江.近红外光谱结合不同变量筛选方法用于黄芩提取过程中黄芩苷含量预测[J]. 药学学报, 2019,54(1): 138-143
2.郭明, 伍周玲, 王春歌, 高小艳.黄芩苷-金属配合物的合成及其抗肿瘤活性研究[J]. 药学学报, 2014,49(3): 337-345
3.祝婧云 梁新丽 王光发 赵国巍 廖正根 曹运朝 陈绪龙 杨 明.白芷提取物对黄芩活性成分黄芩苷的吸收促进作用[J]. 药学学报, 2011,46(2): 232-237
4.陈红艳 耿淼 胡亚卓 王建华.黄芩苷通过上调SIRT1保护SH-SY5Y氧化应激的损伤[J]. 药学学报, 2011,46(9): 1039-1044
5.吴品江 许润春 苏柘僮 魏 萍 林彦君 杨 明 郑 琴.黄芩苷脂质体、β-环糊精包合物及磷脂复合物鼻黏膜渗透性及毒性研究[J]. 药学学报, 2009,44(4): 417-424
6.罗奇志 罗佳波 王有志.高效液相色谱-电喷雾串联四极杆质谱定性分析双黄连粉针中化学成分及其药味归属[J]. 药学学报, 2009,44(12): 1391-1396
7.刘兆明;马越鸣;王天明;郭忻.黄芩苷与黄芩素在离体大鼠肝、肾、小肠及膀胱中代谢的相互转化[J]. 药学学报, 2008,43(6): 664-668
8.居文政;刘芳;吴婷;夏小燕;谈恒山;王醒;熊宁宁.UPLC-MS/MS法同时测定人血浆中黄芩苷和绿原酸[J]. 药学学报, 2007,42(10): 1074-1077
9.冯有龙;余伯阳;董小平.高效液相色谱法同时测定三黄片中的蒽醌类、黄酮类及生物碱类化合物[J]. 药学学报, 2006,41(3): 285-288
10.刘萍;王菊英;李倩;许复郁;王姿颖;徐红岩;刘兆平;张岫美.黄芩苷对大鼠脑缺血再灌注损伤后海马神经元HSP70表达的影响[J]. 药学学报, 2006,41(7): 619-624
11.董庆华;郑树;;徐荣臻;吕庆华.黄芩苷元选择性诱导人白血病K562细胞凋亡[J]. 药学学报, 2003,38(11): 817-820
12.王新宏;安睿;邹云;张艺;王智华;洪筱坤.双黄连片的多组分质量分析[J]. 药学学报, 2001,36(12): 917-920
13.侯艳宁;朱秀媛;程桂芳.黄芩苷的抗炎机理[J]. 药学学报, 2000,35(3): 161-164
14.侯艳宁;程桂芳;朱秀媛.黄芩苷对小鼠肝细胞色素P450的选择性诱导[J]. 药学学报, 2000,35(12): 890-892
15.程智勇;韩凤梅;蔡敏;陈勇.HPCE法测定双黄连口服液中的黄芩苷和绿原酸[J]. 药学学报, 1999,34(11): 854-857