Studies On The Chemical Constituents Of Isodon Rubescens And The Seeds Of Aesculus Chinensis And Their Bioactivities

Isodon rubescens is a plant of the genus Isodon belonging to the family Lamiaceae,which is mainly distributed in Henan,Guizhou,Hebei,Jiangxi,Hubei and other provinces of P.R.China.It is widely used in the treatment of various kinds of inflammation and cancer,especially for esophageal cancer,cardiac cancer,liver cancer.The active constituents of I.rubescens is the ent-kaurane diterpenoids.Previous studies have shown that I.rubescens collected from different provinces contain different structure types of diterpenoids.In consideration of the few reports on the chemical constituents of I.rubescens collected from Hubei Province,a reinvestigation of I.rubescens collected from Badong county,Hubei Province was undertaken by our team.As a result,43 compounds were isolated from the 95%ethanol extract of I.rubescens,including 34 diterpenoids,31 of them were ent-kaurane diterpenoids（1-31）,one of them was ent-atisane diterpenoid（32）,and two of them were ent-abietane diterpenoids（33-34）.The other nine compounds were four triterpenoids（35-38）,three sesquiterpenoids（39-41）.two lignans（42-43）.Among them,compounds 1,2,9-11 and 25 were identified to be five new ent-kaurane diterpenoids.Compound 3 was discovered in natural product for the first time,and compounds 14,19,20,22,26,27,32,and 34-43 were isolated from I.rubescens for the first time.In addition,all the isolated compounds were assessed for their cytotoxicity against some human tumor cell lines（SGC-7901,HepG2,HCT-116,T98,MCF-7）by the CCK-8 method,the results showed that compounds 5and 13 showed anti-tumor activity towards SGC-7901 cells,HepG2 cells and HCT-116 cells,with IC₅₀0 values of 7.31 and 9.02μM,13.30 and 15.51μM,14.25 and12.21μM,respectively.Compounds 3 and 23 displayed anti-tumor activity towards SGC-7901 cells with IC₅₀0 values of 18.21 and 14.26μM.The inhibitory activity against NO production in LPS stimulated RAW264.7 cells of the all compounds were also tested.Compounds 3,5,12,13 and 23 exhibited significant NO production inhibitory effects,with IC₅₀0 values of 3.97,2.25,6.51,1.48 and 1.36μM,respectively.Compounds 4 and 6 showed mild NO production inhibitory effects,with IC₅₀0 values of 17.43 and 18.25μM,respectively.“Suo Luo Zi”is the dry and mature seeds of Aesculus chinensis Bge..It is often used as a stomachic and analgesic to treat distension and pain in chest and abdomen.The main active component in“Suo Luo Zi”are triterpenoid saponins.It has been widely used in clinical medicine for its good anti-inflammation activity,detumescence effect and anti-exudation.In order to discover triterpenoid saponins with interesting structures and biological activities,we made a reinvestigation on the chemical composition of the“Suo Luo Zi”.Finally,15 compounds,including 11triterpenoid saponins（44-54）,three phenolic glycosides（55-57）and a nitrogen glycoside（58）,were obtained from the 60%ethanol extract of“Suo Luo Zi”.Compounds 44-48 are five new compounds.Compounds 49,52,and 55-58 were isolated from“Suo Luo Zi”for the first time.