Study on the interaction between volatile oil components and skin lipids based on molecular docking techniques

Objective To analyze the interactions between different structural types of volatile oil compo-nents(VOCs)and skin lipid molecules;and investigate the mechanism of volatile oil in Chi-nese materia medica(VOCMM)as penetration enhancers.Methods In this study;210 different structural types of VOCs were selected from the VOCMM penetration enhancer database;and the molecular docking experiments were conducted with three main lipid molecules of skin:ceramide 2(CER2);cholesterol(CHL);and free fatty acid(FFA).Each VOC was docked individually with each lipid molecule.Cluster analysis was used to explore the relationship between the binding energy of VOCs and their molecular struc-tures.Nine specific pathogen-free(SPF)Sprague Dawley(SD)rats were randomly divided in-to Control;Nootkatone;and 3-Butylidenephthalide groups for in vitro percutaneous experi-ments;with three rats in each group.The donor pool solutions were 3%gastrodin;3%gas-trodin+3%nootkatone;and 3%gastrodin+3%3-butylidenephthalide;respectively.The pen-etration enhancing effects of VOCs with higher binding energy were evaluated by comparing the 12-hour cumulative percutaneous absorption of gastrodin(Q12;µg/cm²).Results(i)Most of the VOCs were non-hydrogen bonded to the hydrophobic parts of CHL and FFA;and hydrogen bonded to the head group of CER2.Among them;sesquiterpene ox-ides showed the most pronounced binding affinity to CER2.The VOCs with 2-4 rings(in-cluding carbon rings;benzene rings;and heterocycles)demonstrated stronger binding affini-ty for three skin lipid molecules compared with the VOCs without intramolecular rings(P<0.01).(ii)According to the cluster analysis;most of the VOCs that bond well to CER2 had 2-3 intramolecular rings.The non-oxygenated VOCs were bonded to CER2 in a hydrophobic manner.The oxygenated VOCs were mostly bonded to CER2 by hydrogen bonding.(iii)The results of Franz diffusion cell experiment showed that the Q12 of Control group was 260.60±25.09µg/cm2;and the transdermal absorption of gastrodin was significantly increased in Nootkatone group(Q12=5503.00±1080.00µg/cm²;P<0.01).The transdermal absorption of gastrodin was also increased in 3-Butylidenephthalide group(Q12=495.40±56.98µg/cm²;P>0.05).(iv)The type of oxygen-containing functional groups in VOCs was also an influencing factor of binding affinity to CER2.Conclusion The interactions between different types of VOCs with different structures in the VOCMM and three skin lipid molecules in the stratum corneum were investigated at the molecular level in this paper.This research provided theoretical guidance and data support for the screening of volatile oil-based penetration enhancers;and a simple and rapid method for studying the penetration-enhancing mechanism of volatile oils.

一种百合甾体皂苷纯度及糖链结构核磁共振法分析

采用多种NMR分析技术,首次对百合甾体皂苷(25R,26R)-26-甲氧基螺甾烷-5-烯-3β-O-α-L-鼠李糖-(1→2)-[β-D-葡萄糖-(1→6)]-β-D-葡萄糖苷的1H和13C NMR信号进行了全归属,特别是应用选择性的1D TOCSY和1D NOESY核磁共振分析技术,对该化合物1中的氢谱信号严重重叠的糖链进行了详细的分析,提出了一套对甾体皂苷糖链信号进行全归属的核磁共振法。在确认其结构的基础上,建立了核磁共振法(1H NMR)测定该化合物1的纯度,给出了完整的实验条件,线性回归系数为0.9998,重复性实验RSD为0.58%,稳定性实验RSD为0.24%,操作简单、快速准确,且不需要其它对照品,是中药化学对照品纯度研究的一个有益补充。

Investigation of the active components and mechanism of Sanao Decoction in treating chronic cough by network pharmacology and molecular docking

Objective To investigate the active components and mechanism of Sanao Decoction(三拗汤,SAD)in treating chronic cough based on network pharmacology and molecular docking.Methods Active components and their targets were obtained from the Traditional Chinese Medicine Systems and Pharmacology Database and Analysis Platform(TCMSP),Bioinformatics Analysis Tool for Molecular mech ANism of Traditional Chinese Medicine(BATMAN-TCM)database,and the literature.The component-target regulatory network and protein-protein interaction(PPI)network were constructed by Cytoscape 3.7.2,and a bioinformatics analysis was performed to identify the significant pathways and their relevant targets.Molecular docking of the core active components and relevant targets was performed.Results A total of 98 active components of SAD and the corresponding 113 drug targets were identified.The component-target regulatory network and PPI network were successfully established.Results of the bioinformatics analysis indicated that 2281 Gene Ontology(GO)terms were enriched in chronic cough,including 2062 terms were in biological processes,77 in cellular components,and 142 in molecular functions,and top 20 significant pathways in Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Molecular docking study demonstrated that quercetin,luteolin,kaempferol,and naringenin were in good agreement with the corresponding targets.Conclusion The active compounds of SAD,such as quercetin,luteolin,kaempferol,and naringenin,may act on AKT1,MAPK1,RELA,EGFR,and Bcl-2 and regulate the PI3 K-Akt signaling pathway,AGE-RAGE signaling pathway,and fluid shear stress and atherosclerosis pathway to exert the effects of anti-inflammatory,anti-airway remodeling,anti-oxidant stress effects,and repair airway damage,thus treating chronic cough.

Explanation of Gegen Qinlian Decoction Syndrome and Its Clinical Application

Gegen Qinlian Decoction is one of the commonly used classical prescriptions,which consists of fourherbs:Gegen(Puerariae Lobatae Radix),Huangqin(Scutellariae Radix),Huanglian(Coptidis Rhizoma),and Zhigancao Glycyrrhizae Radix et Rhizoma Praeparata cum Melle.The clinical application experience of Gegen Qinlian Decoction is as follows:first,according to Zhongjing Zhang's original text,heat distressing the large intestine with unresolved exterior syndrome is theoriginal meaningof Gegen Qinlian Decoction syndrome.In clinical practice,bacillary dysentery,gastrointestinal cold,etc.,belong to simultaneous exterior and interior disease,which are completely consistent with the original meaning of this prescription;second,the clinical digestive system diseases with exuberant heat of the large intestine as the core manifestation cannot be treated merely based on the exterior syndrome;third,due to the interior-exterior relationship between the lung and the large intestine and between the meridians,the use of Gegen(Puerariae Lobatae Radix),Huangqin(Scutellariae Radix),and Huanglian(Coptidis Rhizoma)can make the source of body clear,and the waste qi can be released and thepore can be easily opened,so this prescription can also be used for exogenous fever;fourth,with multidimensional comprehensive understanding of the syndrome,pathogenesis,symptoms and pharmacology,Gegen Qinlian Decoction has also been further applied to the treatment of hypertension,diabetes,etc.

The Mechanism of Action of Qihuang Jiangtang Capsule in the Treatment of Type 2 Diabetes Based on Network Pharmacology and Molecular Docking Technology

Objective Our objective was to investigate the potential mechanism of action of Qihuang Jiangtang capsule(QHJTC)in the treatment of type 2 diabetes mellitus(T2DM)through network pharmacology and molecular docking.Methods The active components of materia medica in the formula of QHJTC were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine.The targets related to the active components were obtained via PubChem database.The targets related to T2DM were retrieved through the GeneCards database.The targets corresponding to the active components and diabetes mellitus were uploaded to the Venn diagrams website to get the Venn diagram,and the intersecting targets were the potential targets of QHJTC in treating T2DM.The active components and potential targets were imported into Cytoscape 3.7.2 software to construct the active component–potential target network,and the key compounds and targets were screened by the Network Analyzer module in the Tools module.The potential targets were imported into the STRING database to obtain the interaction relationships,so as to analyze and construct the protein–protein interaction(PPI)network by Cytoscape 3.7.2 software.The intersecting targets were introduced into Metascape for gene ontology(GO)functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The top 20 signaling pathways obtained by the KEGG pathway enrichment analysis and the related targets and the corresponding targets were analyzed by using Cytoscape 3.7.2 software to construct the“active component–important target-key pathway network”for the intervention of T2DM with QHJTC.The molecular docking of active components and core targets was performed with AutoDock software.Results A total of 237 active components and 281 related targets were obtained from QHJTC,as well as 1362 T2DM targets and 155 potential targets of QHJTC in treating T2DM.There were 32 key components and 49 key targets identified by the active component–potential target network topology analysis.There were 471 terms obtained from GO functional enrichment analysis,among which 248 related to biological processes,125 related to molecular functions,and 98 related to cellular components.There were 299 signaling pathways obtained from KEGG pathway enrichment analysis.The active components of QHJTC were found spontaneously binding to the core targets.Conclusions QHJTC can treat T2DM through multi-components,multi-targets,and multi-pathways.

Chemical comparison of Semen Euphorbiae and Semen Euphorbiae Pulveratum by UPLC-Q-TOF/MS coupled with multivariate statistical techniques

In the present study,we aimed to assess the chemical composition changes of Semen Euphorbiae(SE)and Semen Euphorbiae Pulveratum(SEP)by UPLC-Q-TOF/MS and multivariate statistical methods.The UPLC-Q-TOF/MS method and SIMCA-P software were used to analyze the changes of chemical components of SE and SEP based on PCA and PLS-DA multivariate statistical methods.A"component-target-disease"network model was constructed by Intelligent Platform for Life Sciences of traditional Chinese medicine(TCM)to predict potential related diseases.The differences of chemical composition were significant between SE and SEP.Under positive ion mode,the amounts of Euphorbia factor L2,L3,L7a,L8,L9 and lathyrol were obviously decreased after processing.Under negative ion mode,the amounts of aesculetin,bisaesculetin,ingenol and cetylic acid were increased obviously,while Euphorbia factor L1,L4 and L5 were decreased obviously after processing,and the components of euphobiasteroid,aesculetin,lathyrol and linoleic acid among the 14 differentiated compounds were closely related to the SE-related diseases through the"component-target-disease"network model.UPLC-Q-TOF/MS technology in combination with multivariate statistical methods had certain advantages in studying the complex changes of chemical composition before and after manufacturing pulveratum of SE.It provided a basis for clarifying the toxicity-attenuated mechanisms of SE manufacturing pulveratum,and laid the foundation for its further development and utilization.

Integrating ancient and modern approaches to traditional Chinese medicinal authentication

Authentication is a key component of quality control,and the quality of Chinese medicinal materials directly impacts clinical efficacy.Chinese medicinal quality control is an important concern of the wider community,and it is intricately connected to the future and development of Chinese medicine.Macroscopic identification has been used for thousands of years in Chinese medicine,and it continues to be effective for resolving important issues related to quality control in the modern-day.However,new challenges have emerged for macroscopic identification.For example,new botanical varieties have emerged,with differences in macroscopic features related to cultivated vs.wild materials.Changes in processing methods and cultivation techniques also affect these features.Consequently,continual progress and innovation in Chinese medicinal authentication methods are needed.Macroscopic identification is based on organoleptic assessment,microscopy,and research of ancient texts,such as the Bencao.In addition to collecting information from traditional experience-based differentiation,innovation can take advantage of new technologies that can provide even more detailed,precise information about morphology.In the present review,we summarized inheritance and innovation in the scientific exposition of Chinese medicinal authentication,featuring a review of specialized publications,description of the establishment of a Chinese medicine specimen center and Chinese Medicine digital project,the expansion of authentication technologies,and the formation of a cultural project dedicated to the Compendium of Materia Medica.

Comparative study on main compounds in Ginkgo biloba L. base on mathematical statistics

In this paper,an HPLC-DAD-ELSD method was developed to determine main 20 components of Ginkgo biloba L.leaves from different ages and sources,including six flavonol glycosides,five terpene lactones and nine organic acids.Using statistics method and establishing relevant mathematics models,the measured data has proceeded correlation analysis,principal component analysis,and regression statistics and the results showed generality and specific characteristics.We defined p-hydroxybenzoic acid,catechinic,KRcG and ginkgolide A as characteristic indexes representing commonness and speciality of Ginkgo biloba L.leaf.The four characteristic indexes can reflect the quality of Ginkgo biloba L.leaf,and the intermal relations between them are significant.The contents of other compounds could define the quantity relation with characteristic markers.It simplified the approach of quality control,and provided a basis for quality control of Ginkgo biloba L.

HER-2/EGFR, the major targets for anti-metastasis effect of tetraarsenic oxide on SKBR3 breast cancer cells

Breast cancer is one of the most common female malignant tumors in the world. Although many therapeutic methods for HER-2 positive breast cancer have been developed, the drug resistance and distant metastasis still remain. Tetraarsenic oxide（As_4O_6） has been demonstrated with an anticancer effect on squamous cell carcinoma and cervical cancer. However, there is no report about the relationship between As_4O_6 and HER-2 positive breast cancer. In the present study, we detected the inhibitory efficacy and mechanism of As_4O_6 on the migration and invasion of SKBR3 breast cancer cells using molecular biological methods. The wound-healing assay, matrigel migration assay, transwell invasion assay and cell adhesion assay were used to assess the migration, invasion and adhesion of SKBR3 cells intervened by As_4O_6. Meanwhile, the reverse transcription-PCR and western blotting were performed to investigate the mechanism of As_4O_6 on the migration and invasion of SKBR3 breast cancer cells. The results demonstrated that As_4O_6 could efficiently inhibit the migration and invasion of SKBR3 cells, the HER-2 positive breast cancer cells, and the adhesion of SKBR3 cells was decreased after As_4O_6 treatment. The mechanism revealed that As_4O_6 anticancer efficacy was related to HER-2/EGFR pathways. As_4O_6 exerted its inhibitory effects on migration and invasion in HER-2 positive breast cancer cells by regulating the factors（EGFR, HER-2, Akt, MMP-9） in HER2/ EGFR signaling pathway and other key molecules. In conclusion, the present study indicated that As_4O_6 inhibited the invasion and migration process of HER-2 positive breast cancer SKBR3 cells by negatively regulating the HER-2/EGFR-mediated signaling pathway. These data provided evidence that As_4O_6 might serve as potential anti-metastasis drug for clinical treatment of breast cancer.

Lignanoids from Solanum lyratum

In the present study,we aimed to investigate the chemical constituents from Solanum lyratum.The constituents were separated by column chromatography on silica gel,Sephadex LH-20 and preparative HPLC.Their structures were elucidated by spectroscopic means.A total of 13 compounds were isolated from S.lyraturn and identified as syringin(1),(+)-isolariciresinol(2),(+)-syringaresinol(3),leptolepisol D(4),(-)-secoisolariciresinol(5),(-)-epi-syringaresinol(6),aviculin(7),zhebeiresinol(8),ciwujiatone(9),(-)-(7′S,8S,8′R)-4,4′-dihydroxy-3,3′,5,5′-tetramethoxy-7′,9-epoxylignan-9′-ol-7-one(10),(+)-lariciresinol(11),(+)-pinoresinol(12)and(+)-medioresinol(13).All the compounds were isolated from S.lyratum for the first time.

Chemical constituents of the aerial parts of Glycyrrhiza uralensis and their inhibitory activities against PTP1B andα-glucosidase

In the present study,a total of 11 compounds were isolated from the aerial parts of Glycyrrhiza uralensis,including two new compounds,glycyuralin Q(1)and glycyuralin R(2),and nine known compounds,including licoriphenone(3),orobol(4),trifoliol(5),7,2′,4′-trihydroxy-5-methoxy-3-arylcoumarin(6),11-hydroxy-9(Z),12(Z)-octadecadienoic acid(7),11-hydroxy-9(E),12(E)-octadecadienoic acid(8),licoricone(9),glycyrin(10),and 2′-hydroxyformononetin(11).Structures of the new compounds were identified by 1 D,2 D NMR and HR-MS data analyses.Compounds 1,2 and 10 showed potent inhibitory activities against PTP1 B,with IC50 values of 1.43,4.71 and 3.79μM,respectively.Compounds 2,4 and 10 inhibitedα-glucosidase with IC50 values of 13.61,11.13 and 17.48μM,respectively.