Study On The Division Of "substance Units" Of Volatile Components Of Houttuynia Cordata And Their "quantity-structure-activity" Relationshi

Objective:Based on the supramolecular"imprinting template"theory of traditional Chinese medicine,this paper studied the temporal and geographical dynamic changes of the"imprinting template"of the Houttuynia cordata Thunb.volatile oil.By establishing the"substance units"division method and the mathematical model of kinetics and thermodynamic equilibrium of supramolecular"imprinting template"of traditional Chinese medicine,the quantitative relationship of chemical potential such as quantity,quantity effect and structure-effect among the"substance units"of Houttuynia cordata Thunb.composition group is established,so as to provide new methods and ideas for clarifying the material basis of traditional Chinese medicine efficacy of Houttuynia cordata Thunb.Method:1.Determining and analyzing the chemical components of 417 batches of Houttuynia cordata Thunb.volatile oil from different producing areas,different collection times and different parts by using the GC/MS method to quantitatively characterize the"imprinting template"of each batch of Houttuynia cordata Thunb.volatile oil,and calculate the molecular connectivity index,core index,total statistical moment parameter,information entropy and other parameters of each volatile oil.2.Utilizing GC/MS analysis to obtain the fingerprints of 58 batches Houttuynia cordata Thunb.volatile oil,which divided Houttuynia cordata Thunb.volatile oil component clusters into"substance units"for calculating the chromatographic parameters,total statistical moment parameters,information entropy,information quantity and other parameters of Houttuynia cordata Thunb.volatile oil component clusters"substance units"after integration,and comparing and analyzing the parameter values of fingerprint before and after integration.3.Establishing the kinetic and thermodynamic equilibrium theory and mathematical treatment method for"substance units"of traditional Chinese medicine component clusters to be regressed by linear and nonlinear regression of the topological structure of"substance units"and"substance units"of 58 batches of Houttuynia cordata Thunb.volatile oil component clusters4.By taking the established kinetic equation linear regression equation and thermodynamic nonlinear regression method,the molecular connectivity index and chromatographic parameters of Houttuynia cordata Thunb.volatile oil was analyzed.5.Using CCK-8 assay to determine the anti-lung cancer rate of 58 batches Houttuynia cordata Thunb.volatile oil with different concentrations to lung cancer cells and calculated the IC50 value of each batch by analyzing their inhibition rate.The relationships between the"substance units"and the effect indicators and the topology of the"substance units"and the pharmacodynamic index were analyzed by linear and nonlinear regressions of kinetic and thermodynamic equilibrium equations,respectively.6.Based on network pharmacology mining the main active components of Houttuynia cordata Thunb.volatile oil against lung cancer,in order to find out the belongings of“substance units”to the main active components.Results:1.The total volatile oil of 417 batches of Houttuynia cordata was measured by GC/MS with 2425 chemical components,only 2-Undecanone,1-Nonanol,Caryophyllene,2-Dodecanone,n-Decaldehyde were found in each batch.Appearance,accounting for less than3%of each batch of volatile oil types,but the content can account for more than 20%,and the composition and content of each batch of volatile oil were varying.The molecular connectivity index,material core index,total statistical moment parameter and information entropy parameter of each batch of volatile oil were obtained by calculation.Through statistical analysis,it was found that the RSD of the peak number,peak area,and information content of 417 batches of Houttuynia cordata volatile oil was relatively high.They are 28.2%,91.47%,and 98.23%respectively.The total first-order moment,information entropy,and the RSD of Xvp zero stage to seventh order are relatively small,especially the Xvp zero-order,Xvp first-order,Xvp The second-order RSDs are small,9.59%,10.58%,and 10.23%,respectively.2.58 batches of Houttuynia cordata volatile oil were divided into"substance units"by matching frequency method,and 34 peaks were divided from the original 332 peaks.The number of original peaks,peak area and information content of Houttuynia cordata volatile oil fingerprint,the RSD of second-order moment was large,while the change of first-order moment and information entropy of total statistics was small,indicating that the composition ratio of Houttuynia cordata volatile oil was relatively stable,and the content of components fluctuated,It just reflects the random and dynamic characteristics of"imprinting template"modified into a single component;In addition,the RSD of the number of peaks before and after integration changes greatly,while the total statistical moment and the RSD of information entropy and information amount have little difference before and after integration,which further shows that the division method can reduce the peaks while maintaining the original chromatographic information and reduce the difficulty of quality control and analysis of traditional Chinese medicine.3.Through the kinetic and thermodynamic regression processing of 58 batches of Houttuynia cordata"substance units",the results of thermodynamic nonlinear regression were better（R²=0.998,p<0.001）,and it was found that No.32,10,4,14,The chemical potential of 13"substance units"ranks high,so it is speculated that these several component groups"substance units"play a major role in the metabolism of Houttuynia cordata.In the same way,the topological structure of each"substance unit"of Houttuynia cordata is analyzed,and the chemical potential of the topological index of the 1st,2nd,4th,3rd,and 14th orders is finally obtained.It occupies the main position in the spatial topology of Houttuynia cordata.Finally,using the optimal ranking of the"quantity"among the component groups and the ranking of the"structure"of the topological structure of the component groups for data integration,it is inferred that the molecular connectivity index of the most stable"imprint template"of the Houttuynia cordata volatile oil component group is:The molecular connectivity indices are:Xvp zero order is 8.6870,Xvp first order is 5.1285,Xvp second order is 4.2288,Xvp third order is 2.7817,Xvp fourth order is 1.8560,Xvp fifth order,1.2432,Xvp sixth order is 0.8159,Xvp seventh order is 0.3796,Xvc third order is 0.7599,Xvc fourth order is 0.0690,Xvc fifth order is 0.1991,Xvc sixth order is 0.0533,Xvc seventh order is 0.0038,Xvpc fourth order is1.3430,Xvpc fifth order is 1.6056,Xvpc sixth order The order is 2.2036,the seventh order of Xvpc is 2.6694,the third order of Xvch is 0.0223,the fourth order of Xvch is 0.0649,the fifth order of Xvch is 0.1283,the sixth order of Xvch is 0.1977,and the seventh order of Xvch is 0.2625.4.By performing linear regression of kinetic equation and nonlinear regression of thermodynamic equation on the molecular connectivity index of"substance unit"of Houttuynia cordata volatile oil and chromatographic parameters,it was found that the"imprint template"structure of Houttuynia cordata component group was closely related to chromatographic column.Thermodynamic control,obtained the corresponding 22-order average molecular connectivity index chemical potential of Houttuynia cordata after correlation,found that Xvp third-order,Xvp zero-order,Xvp second-order,Xvp fourth-order,Xvpc fourth-order ranked high,speculate that these order molecules The connectivity index has a great influence on the chromatographic peak time,so the relationship between the"imprint template"structure of each cluster of Houttuynia cordata and the chromatographic parameters can be analyzed.5.Through the study of 58 batches of Houttuynia cordata volatile oil on anti lung cancer proliferation by CCK-8 detection method,it was found that the inhibition rate of Houttuynia cordata volatile oil on A549 cells gradually increased with the increase of drug concentration,and the IC₅₀ value of each batch of volatile oil on anti lung cancer was 0.0736μL/m L-0.2699μL/m L。Houttuynia cordata"substance unit"and effect index,as well as"substance unit"topology and efficacy index are controlled by thermodynamics.In the"dose-effect"correlation,it was found that the positive chemical potential of the"substance unit"inhibited lung cancer cells,and the larger the value,the better the anti-cancer effect.Among the 34"substance units",17 substance units were positive Directional action,respectively 32,29,27,10,3,17,12,25,6,18,19,31,22,16,28,11,15"substance units".In the"structure-effect"correlation,it is found that the sum of the topological chemical potentials of the"substance units"in paragraphs 10,22,25,2,and 15 is the"structure"of the"imprint template"component group of Houttuynia cordata which has a relatively large effect on the medicinal effect..6.The main active components of Houttuynia cordata volatile oil against lung cancer were discovered by network pharmacology as 2-Undecanone,1-Undecanol,n-Decanoic acid,Undecanoal,Docosanoic acid,ethyl ester,and found that they belonged to Articles 19,22,and 22,respectively.,19,32"substance units",these"substance units"also belong to the 17positive action units associated with Houttuynia cordata"dose-effect"in Chapter 6.Conclusion:Through the characterization results of 417 batches of Houttuynia cordata"imprint templates",it is found that the material core index（Xvp zero order,Xvp first order,Xvp second order）,the first order total statistical moment,the"three stability"of information entropy,And the"three instability"law of peak number,peak area,and amount of information.This law reveals that the components of Chinese medicinal materials as a whole follow the law of supramolecular autonomous action,are stable in the structure and imprinting effect of the"imprinted template",and have thermodynamic and kinetic stability of the component group"substance unit"centered on the"imprinted template".,while the individual and content modified into specific components vary with the domain and the strain at any time.The established supramolecular"imprinting template"imprinting kinetics and thermodynamic equilibrium principle and mathematical model can better explain the quantity-quantity,structure-structure,structure-imprint,quantity-effect,structure-effect,etc.The quantitative relationship between structure and effect of chemical potential was finally obtained.To provide new methods and new ideas for elucidating the pharmacodynamic material basis of traditional Chinese medicine Houttuynia cordata and the mechanism of action of its multi-component groups.