RESUMO
With the widespread use of traditional Chinese medicine(TCM) and the integration of TCM and western medicine, drug-drug interaction(DDI) is considered as a major cause of therapeutic failures and side effects. Cytochrome P450 enzymes(CYPs) are responsible for large number of drug metabolism. CYP3 A4 and CYP2 D6, two important CYP isoforms, are responsible for about 80% drug metabolism of CYPs super family. The inhibition of CYPs is likely to be the most common factor leading to adverse DDI. Therefore, it is of great significance to predict potential CYP3 A4 and CYP2 D6 inhibitors to prevent the DDI. A fast and low-cost me-thod for calculating and predicting CYP inhibiting components was established in this paper, namely support vector machine(SVM) and molecular docking technology which are used to predict and screen drugs. Firstly, 12 qualitative models of two targets were established by using SVM, and the optimal model was selected to predict the compounds in traditional Chinese medicine database(TCMD). Then, molecular docking technology was used to establish docking model. By analyzing the key amino acids involved in drug-target interactions and combining with SVM model, potential inhibitors of CYP3 A4 and CYP2 D6 were found. From the computational results, astin D and epiberberine exhibited inhibition effect on CYP3 A4 and CYP2 D6, respectively. Astin D was only found in astins family from Aster tataricus, while epiberberine was considered to be the active constituent of Coptidis Rhizoma. Therefore, for the risk of DDI, extra attention should be paid to the source of these potential inhibitors, Asteris Radix et Rhizoma and Coptidis Rhizoma. This computational method provides technical support for discovering potential natural inhibitors of CYPs from Chinese herbs by using SVM and molecular docking model, and it is also helpful to recognize the CYPs-mediated DDI existing in TCM, providing research ideas for further pharmacovigilance of integrated therapy.
Assuntos
Inibidores das Enzimas do Citocromo P-450/análise , Medicamentos de Ervas Chinesas/química , Sistema Enzimático do Citocromo P-450 , Medicina Tradicional Chinesa , Simulação de Acoplamento Molecular , Plantas Medicinais/químicaRESUMO
Near infrared (NIR) spectroscopy assignment of Magnolol was performed using deuterated chloroform solvent and two-dimensional correlation spectroscopy (2D-COS) technology. According to the synchronous spectra of deuterated chloroform solvent and Magnolol, 1365~1455, 1600~1720, 2000~2181 and 2275~2465 nm were the characteristic absorption of Magnolol. Connected with the structure of Magnolol, 1440 nm was the stretching vibration of phenolic group O-H, 1679 nm was the stretching vibration of aryl and methyl which connected with aryl, 2117, 2304, 2339 and 2370 nm were the combination of the stretching vibration, bending vibration and deformation vibration for aryl C-H, 2445 nm were the bending vibration of methyl which linked with aryl group, these bands attribut to the characteristics of Magnolol. Huoxiangzhengqi Oral Liduid was adopted to study the Magnolol, the characteristic band by spectral assignment and the band by interval Partial Least Squares (iPLS) and Synergy interval Partial Least Squares (SiPLS) were used to establish Partial Least Squares (PLS) quantitative model, the coefficient of determination Rcal(2) and Rpre(2) were greater than 0.99, the Root Mean of Square Error of Calibration (RM-SEC), Root Mean of Square Error of Cross Validation (RMSECV) and Root Mean of Square Error of Prediction (RMSEP) were very small. It indicated that the characteristic band by spectral assignment has the same results with the Chemometrics in PLS model. It provided a reference for NIR spectral assignment of chemical compositions in Chinese Materia Medica, and the band filters of NIR were interpreted.
Assuntos
Compostos de Bifenilo/química , Medicamentos de Ervas Chinesas/química , Lignanas/química , Espectroscopia de Luz Próxima ao Infravermelho , Análise dos Mínimos Quadrados , Modelos Teóricos , FenóisRESUMO
The present paper firstly reviewed the research progress and main methods of NIR spectral assignment coupled with our research results. Principal component analysis was focused on characteristic signal extraction to reflect spectral differences. Partial least squares method was concerned with variable selection to discover characteristic absorption band. Two-dimensional correlation spectroscopy was mainly adopted for spectral assignment. Autocorrelation peaks were obtained from spectral changes, which were disturbed by external factors, such as concentration, temperature and pressure. Density functional theory was used to calculate energy from substance structure to establish the relationship between molecular energy and spectra change. Based on the above reviewed method, taking a NIR spectral assignment of chlorogenic acid as example, a reliable spectral assignment for critical quality attributes of Chinese materia medica (CMM) was established using deuterium technology and spectral variable selection. The result demonstrated the assignment consistency according to spectral features of different concentrations of chlorogenic acid and variable selection region of online NIR model in extract process. Although spectral assignment was initial using an active pharmaceutical ingredient, it is meaningful to look forward to the futurity of the complex components in CMM. Therefore, it provided methodology for NIR spectral assignment of critical quality attributes in CMM.
Assuntos
Medicamentos de Ervas Chinesas/normas , Materia Medica/normas , Espectroscopia de Luz Próxima ao Infravermelho , Ácido Clorogênico , Medicamentos de Ervas Chinesas/análise , Análise dos Mínimos Quadrados , Materia Medica/análise , Análise de Componente PrincipalRESUMO
Multivariate detection limits (MDLs) of different types of near-infrared instruments were investigated to guide the selection of device type for TCM NIR analysis. In this paper, near-infrared spectroscopy of Qingkailing injection was performed in transmission mode on four near-infrared spectrometers named a, b, c and d, respectively. High performance liquid chromatography (HPLC) was used as the reference method to determine the content of baicalin in Qingkailing injection. Partial least squares (PLS) and interval partial least squares (iPLS) quantitative models of baicalin in Qingkailing injection were established and MDLs of quantitative models based on different types of instruments were calculated. The determination coefficient of prediction (R2(pre))and the root mean square errors of prediction (SEP) of PLS models of four different near-infrared spectrometers are 0.9762 and 230.4 microg x mL(-1) (a), 0.9561 and 246.4 microg x mL(-1) (b), 0.9662 and 264.4 microg x mL*-1) (c), 0.9985 and 71.5 microg x mL(-1) (d). And the model of instrument d shows a better prediction performance than the other three types. There are no remarkable superiorities in predictability in iPLS models of instruments a and b after variable selection, since the R2(pre) and SEP values for instruments a and b are 0.9771 and 218.4 microg x mL(-1), and 0.9754 and 219.4 microg x mL(-1), respectively. Models c and d show no results of variable selection. MDLs (delta(0.05, 0.05) of different instruments are all less than 250 microg x mL(-1), and the MDLs of instruments c and d reach to 58 and 2.9 microg x mL(-1) respectively. The results reveal that the predictability of models and corresponding MDLs are different for different detection equipments. This paper innovatively used the theory of MDL to investigate the detection performance of different types of NIR instruments. The results demonstrated the feasibility of the approach. And it is expected that in actual applications, choosing the right type of instrument should be based on the characteristics of the study carrier to ensure quantitative accuracy.