Chemical Constituents From The Rhizome Of Atractylodes Japonica And Their Inhibitory Effect On Tumor Cell Proliferation

Atractylodes japonica Koidz.ex Kitam.,a perennial herb that belongs to the family Asteraceae and the genus Atractylodes,is mainly distributed in Heilongjiang,Liaoning,Jilin.The rhizome A.japonica has the efficacy of invigorating the spleen and removing dampness,sweating and relieving eyesight,expelling wind,and removing foulness.Previous phytochemical and pharmacological investigations revealed the presence of sesquiterpenes,alkynes,phenols,coumarins isolated from A.japonica and exhibited anti-tumor,anti-inflammatory,anti-oxidant,antibacterial.In order to elucidate the chemical constituents and their pharmacological activity from this plant,the study were conducted in the of petroleum ether extract and ethyl acetate extract from the rhizome of A.japonica,using silica gel column,MPLC and HPLC.Twenty-three compounds were identified by NMR and other spectroscopic methods,including four sesquiterpenes:atractylenolide II（1）,atractylenolide III（2）,atractylon（3）,eudesm-4（15）,7-diene-9a,11-diol（4）,two alkynes:（6E,12E）-6,12-tetradecadiene-8,10-diyne-1,3-diol（5）,（6E,12E）-tetradecadiene-8,10-diyne-1,3-diol diacetate（6）,three phenols:2-[（1E）-2-（3,4,5-trimethoxyphenyl）ethenyl]phenol（7）,4,5-dihydroxyphenyl（8）,4-（1-methoxyphenyl）-1,2-propanediol（9）,one phenylpropanoid:3-（4,5-dihydroxyphenyl）-2-propenoic acid（10）,three coumarins:scopoletin（11）,scoparone（12）,7-hydroxycoumarin（13）,two glycosides:2-phenylethyl-O-β-D-glucopyranoside（14）,siphonoside（15）,two hemiterpenoids:3-（hydroxymethyl）-2,5-dihydrofuran-2-one（16）,2-deoxy-D-ribono-1,4-lactone（17）,one indole:indole-3-carboxaldehyde（18）,two sterols:β-sitosterol（19）,7α-hydroxy-β-sitosterol（20）and two aliphatics:1-glyceryl linoleate（21）,9（S）,12（S）,13（S）-trihydroxyoctadeca-10（E）,15（Z）-dienoic acid（22）,one aldehyde:5-methoxyfurfural（23）.Among them,compound 4 was isolated from A.japonica for the first time,compounds 15 and 16 were found in the genus Atractylodes for the first time.Inhibitory effect of compounds 1-23 on the proliferation of He La,Hep G₂and A549 cell lines were determined by the MTT method.Compounds 1-3,5,11 and 12exhibited moderate cytotoxicities against the He La cells with half-maximal inhibitory concentrations(IC₅₀)values of 10.94±0.47,14.46±0.62,18.03±0.21,15.23±0.21,23.03±0.22,25.03±0.21μM,respectively,against A549 cells with IC₅₀values of18.57±0.64,16.01±0.40,15.43±0.12,14.13±0.12,24.40±0.14,22.43±0.16μM,respectively,and against Hep G2 cells with IC₅₀values of 16.30±0.52,18.69±0.47,12.34±0.63,11.36±0.36,21.30±0.53,23.22±0.13μM,respectively.This results not only enriched the chemical constituents of A.japonica,but also provided a theoretical basis for the further study and utilization of A.japonica resources.