ABSTRACT
Objective: To identify potential SARS-CoV-2 3CL protease inhibitors from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) by molecular docking approach. Methods: To alternate extensive compounds experimental screening processes, a Computer-Aided Drug Design (CADD) based molecular docking technology was performed to explore existing drug repurposing possibilities. Molecular docking model with Schrodinger suit 2018 was used to evaluate the binding abilities between TCMSP 13 143 compounds and SARS-CoV-2 3CL protease receptor-binding domain (PBD ID 6LU7), which involving in mediating viral replication and transcription functions. According to the constructed docking system, potential compounds were screened according to docking score, oral bioavailability (OB), and drug-likeness (DL). At last, a compounds-herb-target organ-function network was constructed. Results: Compared with 6LU7 original ligand docking score (-7.734), a total of 498 compounds were identified with lower docking score against 6LU7 targets. These compounds were further reduced to 60 high-priority compounds, based on OB (more than 30) and DL (more than 0.18). Meanwhile, these 60 compounds were found to interact with the amino acid residues (GLU166, GLY143, ASP187, CYS145, GLN189, LEU141, etc.) which were critically involved in the 6LU7 domain mainly by hydrogen-bonded interaction. The network exploring results revealed that these potential compounds were mainly attributed to Glycyrrhizae Radix et Rhizoma, Mori Cortex, Rhododendron dauricum, Polygoni Cuspidati Rhizoma et Radix, and Plantaginis Herba, etc., which associates with acute lung syndromes induced by SARS-CoV-2, with the effect of clearing heat and removing toxin, relieving cough and dispelling phlegm and lung-draining and relieving asthma. Conclusion: Molecular docking method provides a useful tool for the screening of SARS-CoV-2 3CL protease inhibitors from TCMSP platform.
ABSTRACT
A UPLC method has been developed for simultaneous determination of nine furanocoumarins of Angelica dahurics,and was used for quality evaluation of A. dahurica from different habitats. ACQUITY UPLC BEH C18 chromatographic column was employed,the separation was performed with the mobile phase consisting of acetonitrile and water,and the detection wavelength was set at254 nm. This method was used to simultaneously determine the content of xanthotoxol,oxypeucedaninhydrate,byak-angelicin,psoralen,xanthotoxin,bergapten,oxypeucedanin,imperatorin and isoimperatorin in A. dahurica from different habitats. Then,the further quality assessment of the drug was carried out by similarity evaluation,cluster analysis( CA),principal component analysis( PCA),and orthogonal partial least squares discriminant analysis( OPLS-DA). The content order of measured furanocoumarins from high to low was: oxypeucedanin>imperatorin>isoimperatorin>oxypeucedaninhydrate>bergapten>byak-angelicin>xanthotoxin>xanthotoxol>psoralen,with the mean content 2. 844,1. 277,0. 649 2,0. 216 2,0. 129 8,0. 062 68,0. 052 68,0. 019 30,0. 018 19 mg·g-1,respectively. There were difference between the batches of the drug,and the quality was influenced by smouldering sulphur based on the results of chemical pattern recognition and content determination. Finally,six active ingredients were recognized as the quality makers using OPLS-DA method. The validated UPLC fingerprint combined with chemical pattern recognition method can be used in the quality control and evaluation of A. dahurica.
Subject(s)
Angelica , Chemistry , Chromatography, High Pressure Liquid , Drugs, Chinese Herbal , Reference Standards , Ecosystem , Furocoumarins , Quality ControlABSTRACT
Objective This study aimed to establish an integral quality control method for Naoxintong capsules based on the theory of quality markers (Q-marker) in traditional Chinese medicine via multivariable statistical calculation and "active compounds-targets" network construction. Methods Multi-statistical methods were firstly carried out to explore the specific components from different batches of Naoxintong Capsules. The "Q-markers-targets-pathways-diseases" network was constructed using the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) online analysis tool, and biological information annotations were made. Moreover, a simultaneously determination method for Q-markers was established by using ultra-high performance liquid chromatography (UPLC). Results Nine compounds were chose as the Naoxintong Q-markers capsules including mulberroside A, hydroxysafflor yellow A, paeoniflorin, ferulic acid, calycosin-7-glucoside, rosemary acid, salvianolic acid B, formononetin, and tanshinone IIA. To verify the prediction, target network construction analysis was performed and indicated that the nine Q-markers mainly targeted five proteins which were PTGIS, PTGS2, CHRNA10, ENPP1, and ADORA2A. Methodological validation showed that the established UPLC method had good linear relationship (r<0.999), and all RSD values were lower than 3% in the repeatability, stability, and precision test. Conclusion Based on the multivariate statistics, network pharmacology analysis, and UPLC multi-component quantitative analysis, a multi-angle analysis method for effective components can be established for the integral quality control of Naoxintong Capsules.
ABSTRACT
To explore the flavor and meridian tropism classification of Callianthemum taipaicum by principal components analysis(PCA) and partial least square analysis(PLS). Meanwhile,to establish a high performance liquid chromatography-tandem mass spectrometry(HPLC-ESI-MS) method for the simultaneous determination of 55 active components from 13 kinds of Ranunculaceae of Chinese traditional herbs. Samples were separated on HPLC system by Agilent 5 TC-C₁₈（2）（4.6 mm×250 mm，5 μm）column and eluted with acetonitrile and 0.1% formic acid at the flow rate of 0.6 mL·min⁻¹. The data were performed by HPLC-ESI-MS with multiple reaction monitoring（MRM）scanning mode under positive and negative ion modes and quantified by external standards. The data from 13 Ranunculaceae herbs were analyzed by the PLS-tree and cooman's prediction of PCA and PLS to evaluate the similarities and differences of C. taipaicum in flavor and meridian tropism. The results showed that calibration curves of 55 components all showed good linearity, >0.99,with good precision, repeatability and stability. After compared to other 12 herbs,PCA and PLS results revealed that the C. taipaicum belonged to lung and bladder meridians while its flavor attributive to pungent,warm in nature. In conclusion,the analysis approach of chemometric calculation combined with multi-components quantification is suitable for the classification of meridian tropism and flavor of Chinese traditional medicine,which can be used for alternative research of rare herbs.