Study On The Chemical Constituents From The Stems And Leaves Of Morinda Citrifolia And Their Biological Acitivities

Morinda citrifolia is a perennial evergreen broad-leaved shrub or dungarunga belonging to the genus Morinda in the family of Rubiaceaec,which grows in tropical and subtropical areas.More than 2000 years ago,its roots,stems,leaves,skin,flowers and fruits were used as folk medicine by the indigenous people of the Polynesia.M.citrifolia is widely believed to treat chronic diseases such as diabetes,arthritis,high blood pressure and heart disease,and it has good curative effect in skin diseases and wound infections and pain caused by knife and gunshot wounds.Modern pharmacological research showed M.citrifolia has anti-diabetes,anti-bacterial and anti-tumor effects.In order to develop and utilize the folk medicinal value of this plant more reasonably and effectively,and to clarify the chemical constituents pharmacodynamic material basis of M.citrifolia,the chemical constituents and the biological activities of M.citrifolia were systematically studied in this paper.The dry stems and leaves of M.citrifolia were crushed and extracted with 90%ethanol.The 90%ethanol extract of the stems and leaves of M.citrifolia was suspended in distilled water and extracted successively with petorleum ether（PE）and ethyl acetate（Et OAc）.The PE extract fraction and the Et OAc extract fraction were repeatedly subjected to silica gel CC,Sephadex LH-20 CC,ODS gel CC and semi-preparative HPLC,,respectively.The structures of all isolated compounds were identified by physical and chemical properties and comprehensive spectral analyses.As a result,32 compounds were isolated from M.citrifolia’s ethanol extract and identified as morincitrinoid A（1）,blumenol A（2）,（+）-dehydrovomifoliol（3）,（6R,7E,9R）-9-hydroxy-4,7-megastigmadien-3-one（4）,blumenol C（5）,4-megastigmen-3,9-dione（6）,（6E,9S）-9-hydroxy-4,6-megastigmadien-3-one（7）,vomifoliol（8）,9-hydroxy-5,7-megastigmadien-4-one（9）,rhododendrone（10）,（3S,5R,6S,7E）-5,6-epoxy-3-hydroxy-7-megastigmen-9-one（11）,lyratol F（12）,oleracone B（13）,loliolide（14）,isololiolide（15）,（+）-dehydrololiolide（16）,garjasmine（17）,pubinernoid A（18）,2-hydroxy-1-methoxy-anthraquinone（19）,1,6-dihydroxy-5-methoxy-2-methoxy-methyl-anthraquinone（20）,morindicinone（21）,scopoletin（22）,3-indole formal-dehyde（23）,4-methoxy benzaldehyde（24）,4-hydroxybenzaldehyde（25）,p-coumaric acid（26）,4-methoxy phenylacetic acid（27）,p-hydroxybenzoic acid（28）,vanillic acid（29）,2-hydroxy-4-methoxyl-phenol（30）,4-hydroxybenzoic acid methyl eater（31）and methyl hematinate（32）.Among them,compounds 1-18 were terpenoids,compounds 19-21 were anthraquinones,compound 22 was a coumarin,compounds 23 and 32 were alkaloids and compounds 24-31 were simple phenolic acids.Compound 1 was a new naturaly occurring bisabolane-type sesquiterpenoid,compounds 2-14,16-18,23,24 and 30 were isolated from the genus Morinda for the first time.In addition,the anti-tumor activities of selected compounds isolated from the stems and leaves of M.citrifolia were evaluated in vitro by MTT method.As a result,3,4,6,7,9-12and 17 have significant growth inhibition activities to five various cancer cell lines（HL-60,SMMC-7721,A-549,MCF-7 and SW480）,displaying the IC₅₀values in range of 1.48±0.06-32.46±0.21μM.Furthermore,selected compounds were evaluated for their anti-inflammatory activities via examining their inhibitory activities against NO production by Griess method.As a result.compounds 17,19,21 and 32 exhibited notable inhibitory effects on NO production showing the IC₅₀values ranging from 2.07±0.08 to 18.89±0.16μM,which were comparable to that of hydrocortisone.