基于分子热力学特征探讨中药黄芩的归经特性

Meridian tropism of Scutellaria baicalensis based on molecular thermodynamic characteristics

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(disassociation constant,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。

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.