Chemical Constituents And Biological Activities Of Codonopsis Tangshen Oliv.

Codonopsis tangshen Oliv.is an original plant of Codonopsis Radix.It mainly grows in mountains,forest margins and shrubs and is widely distributed in Hubei,Sichuan,Guizhou,Hunan and Shanxi.It is used to treat spleen and lung qi deficiency,sallow complexion,internal heat and quenching thirst.The chemical constituents and anti-inflammatory activities of C.tangshen were researched in this paper,which provides a scientific basis for the further development and application of this plant.In this paper,the ethyl acetate and petroleum ether extracts of C.tangshen were separated and purified by silica gel column chromatography,Sephadex LH-20 column chromatography and reversed-phase high performance liquid chromatography.The structures were identified by HRMS,¹H-NMR,¹³C-NMR,HMBC,HSQC,CD,NOSEY and other spectral techniques.30 compounds were identified,including 8lignans,9 polyacetylenes,9 fatty acids and 4 phenolic acids.They were identified as（7S,8R）-7’（Z）-hierochin D（1）,mangnostellin D（2）,（7S,8S）-3-methoxy-3’,7-epoxy-8,4’-oxyneoligna-4,9,9’-triol（3）,isolariciresinol（4）,curcasinlignan B（5）,（-）-（7R,8S,7’E）-3’,4-dihydroxy-3-methoxy-8,4’-oxyneoligna-7’-ene-7,9,9’-triol（6）,（7S,8R）-3,4,7,9,9’-pentahydroxy-3’-methoxy-8-O-4’-neolignan（7）,dehydrodieoniferyl alcohol（8）,pilosulyne F（9）,pilosulyne C（10）,（4E,12Z）-threo-tetradeca-4,12-diene-8,10-diyne-1,6,7,14-tetraol（11）,isolobetyol（12）,pilosulynes A（13）,（+）-（6R,7R,12E）-tetradeca-12-en-10-yn-1,6,7-triol（14）,pilosulyne B（15）,tetradeca-4E,8E,12E-triene-10-yne-1,6,7-triol（16）,lobetyol（17）,1-α-linoleoylglycerol（18）,glyceroyl monopalmitate（19）,（8S,9R,10E,12R,14Z）-heptadeca-10,14-diene-1,8,9,12-tetraol（20）,glycerol 1-（9,12,15-octadecatrienoate）（21）,9,12,13-trihydroxy-10（E）-octadecenoic acid（22）,lauric acid（23）,tianshic acid（24）,（9S,10R,11E,13R,15Z）-9,10,13-trihydroxyoctadeca-11,15-dienoic acid（25）,myristic acid（26）,1-（4-hydroxy-3,5-dimethoxyphenyl）propan-1-one（27）,syringic acid（28）,syringic acid ethyl ester（29）,syringaldehyde（30）.Among of them,compound 1 was a new compound,compounds2,5,7,12,19～21,25,27 and 29 were isolated from C.tangshen for the first time.The targets and pathways of C.tangshen were researched by network pharmacology method,the results showed that the related targets include ALB,AKT1,EGFR,CDK2,CASP3,SRC,MMP3,MIF and ESR1,etc;the related pathways include Pathways in cancer,Lipid and atherosclerosis,Proteoglycans in cancer,Prostate cancer and PI3K-Akt signaling pathway,etc;Some of the targets screened out by network pharmacology method were docked with related compounds by molecular docking technology,the results showed that many chemical components,such as curcasinlignan B,（7S,8R）-3,4,7,9,9’-pentahydroxy-3’-methoxy-8-O-4’-neolignan and（7S,8S）-3-methoxy-3’,7-epoxy-8,4’-oxyneoligna-4,9,9’-triol,have good binding ability with inflammation targets,such as MIF,MMP3,AKT and SRC,etc.Based on the results of molecular docking,some chemical components with higher total scores were selected for MIF and AKT enzyme assays.The results showed that curcasinlignan B and（7S,8R）-3,4,7,9,9’-pentahydroxy-3’-methoxy-8-O-4’-neolignan have good inhibitory effect on MIF enzyme;（7S,8R）-7’（Z）-hierochin D and（7S,8R）-3,4,7,9,9’-pentahydroxy-3’-methoxy-8-O-4’-neolignan have good inhibitory effect on AKT enzyme.In summary,the research on the chemical constituents and anti-inflammatory activity of C.tangshen has accumulated new data for the further development and utilization of this plant,which provides a reference for the subsequent development of drugs for the prevention and treatment of inflammation.