The Mechanism Based On Molecular Docking For Four Kinds Of Plant Essential Oil Inhibiting Cancer Cell Proliferation In Vitro

Plant essential oil is secretion which produced by trees or understory commercial crops.For special smell and rich biological activity,plant essential oil is widely used in the food,medicine and cosmetics.Cancer is highly harmful to human health.Chemical synthesis drug is one of the most effective means to treat cancer at present,but it has obvious side effects.Therefore,screening valuable chemical components from natural products is of great significance for developing new means to treat cancer.In this study,cumin essential oil was taken as an example to study the extraction method of plant essential oil based on deep eutectic solvent(green solvent).The results showed that the yield of cumin essential oil extracted by deep eutectic solvent method was 4.36%,which was significantly higher than 3.41%of steam distillation method.On the basis of single factor experiments,the response surface methodology was used to optimize the extraction process.The optimal extraction conditions were as follows:the solid-liquid ratio(raw material-extraction solvent)was 1:5 g/mL,and the molar ratio of the deep eutectic solvent was 1:3.5.(Choline chloride:1,3-butanediol),the water content of the extraction solvent is 45 mol.MTS method combined with light microscope observation method was used to investigate the in vitro inhibitory activity of 23 kinds of plant essential oils on Colon cancer HCT116 cells and Hepatocellular Carcinoma HepG2 cells.The results showed that the four essential oils,cumin,schisandra,tangerine and angelica,had outstanding inhibitory activities,and the highest inhibitory rates on colon cancer HCT116 cells were 54.3%,46.81%,45.83%and 45.42%,respectively.The highest inhibition rate of Hepatocellular Carcinoma HepG2 cells was 42.17%,49.43%,45.95%and 56.2%,respectively.The chemical constituents of cumin,angelica,schisandra and tangerine peel essential oils were qualitatively and quantitatively analyzed by gas chromatographymass spectrometry(GC-MS).The results showed that the chemical components with higher content in the four kinds of essential oil were:cumin essential oil(cuminaldehyde:26.75%);tangerine essential oil((4R)-limonene:88.47%);angelica essential oil(Gymnomitrene:10.90%;ligustilide:3.91%);Schisandra essential oil(rac-Iso-α-cedren15-al:11.48%;ylangene:(6.78%).Computational chemistry methods were used to analyze the relationship between cuminaldehyde,(4R)-limonene,hand ginseng,ligustilide,rac-Iso-a-cedren-15-al,ylangene and the key enzyme protein molecules of colon cancer and liver cancer cell proliferation.Molecular docking was carried out,and the chemical binding energy between the molecules was calculated.The results showed that the binding energies of cuminaldehyde to Glycogen Synthase Kinase 3 Beta(GSK3β)and Aldehyde Dehydrogenase 1 Family Member Al(ALDH1A1)were-6.10 and-7.58 kcal/mol,respectively.The binding energies of(4R)-limonene to Peroxisome Proliferator Activated Receptor Alpha(PPARA)and Cannabinoid Receptor 2(CNR2)were-3.90 and-4.70 kcal/mol,respectively.The binding energies of Gymnomitrene to Hydroxysteroid 11-Beta Dehydrogenase 1(HSD11B1)and UDP Glucuronosyltransferase Family 2 Member B7(UGT2B7)were-6.50 and-6.75 kcal/mol,respectively.The binding energies of ligustilide to Prostaglandin-Endoperoxide Synthase 2(PTGS2)and Transforming Growth Factor Beta Receptor 1(TGFBR1)were-5.50 kJ/mol and6.69 kcal/mol,respectively.The binding energies of rac-Iso-α-cedren-15-al to Androgen Receptor(AR)and Cytochrome P450 Family 19 Subfamily A Member 1(CYP19A1)were-9.09 and-7.39 kcal/mol,respectively.The binding energies of ylangene to Androgen Receptor(AR)and CYP19A1 were-9.19 and-7.80 kcal/mol,respectively.It shows that the molecules form a relatively tight binding relationship through noncovalent interaction.Therefore,these chemical components may be the key substances for the four kinds of plant essential oils to inhibit the proliferation of cancer cells.From the perspective of computational chemistry,the above results reveal the mechanism of plant essential oil inhibiting the proliferation activity of cancer cells.This study provides basic research data for plant essential oils in the field of anticancer,and also expounds the anti-cancer mechanism of essential oils from the perspective of computational chemistry,and explores a green extraction process suitable for plant essential oils.The result expands the utilization and provides references for plant essential oil.