Investigation Of The Chemical Constituents And Biological Activities Of Cornus Officinalis

Cornus officinalis belongs to the genus Cornus of the family Cornaceae,Which is one of the most frequently used 25 traditonal folk medicnes in China,South Korea and Japan.It has been evidenced with potential tonic,analgesic and diuretic effects.Previous phytochemistry and pharmacological studies have shown that the extracts of Cornus officinalis have potential antidiabetic,anti-inflammatory,anti-oxidant,anti-cancer activities.Cardiovascular diseases,cancer,diabetes,along with its associated adverse cardiovascular diseases have become as the three epidemic and serious worldwide public health issue in the 21st century.Unfortunately,the most currently clinical used drugs have certain side effects,such as thiazolidinedione derivatives(TZDs)have been tempered due to their side effects(eg.Edema and increased incidence of heart attack).Owning to the characteristics of multi-target,multidirectionality and less side effects of traditional Chinese medicines,exploring new leads from them with potential anti-diabetics,anticancer with specific targets have raised great interesting.In this thesis,the dried and mature fruit of Cornus officinalis collected at Zhashui County of Shaanxi Province was used as raw materials.And its chemical constituents of the ethanol extract were studied.In addition,the anticancer and the PPARy agonist activity were also evaluated for the isolated compounds.And the major results are summarized as following:(1)Fourteen known compounds(1-14)were isolated from the ethanol extract of the Cornus officinalis by using various spectroscopic techniques,such as regular pressure silica gel column,Sephadex LH-20 gel column and HPLC.Their chemical structures were elucidated based on the 1H and 13C nuclear magnetic resonance(NMR)data,LC-MS,in comparison with the literatures.They are identified as betulinic acid(1),urosic acid(2),isovanillin(3),epoxyconifeiyl alcohol(4),geniposide(5),indomethacin(6),kaempferol(7),palmitic acid(8),vanillic acid(9),pcoumarica acid(10),naringenin(11),(3β)-3-Hydroxyursa-9(11),12-dien-28-oic acid(12),oleanolic acid(13),morroniside(14).respectively.Among them,compounds 3,6,9,12 were isolated from Cornus officinalis for the first time.In addition,the compound indomethacin(6)is the first indoalkaloid isolated from Cornus officinalis.(2)By CTG method,the compounds 1-3,5-8,10-12 were evaluated for their anticancer activity against the human colon cancer cell line HT29.Compounds 1,2,and 12 exhibited good inhibitory activity against HT29 proliferation.(3)In addition,the PPARy agonistic activites for compounds 1-3,5-8,10-12 were also carried out by Cell-based luciferase reporter gene assays and GW9662 block experiments.The results indicated compounds 2 and 7 excited potential agonistic activity for PPARy receptor with relative fluorescence intensity of 24.14 at 10 μM and 17.02 at 100 μM.Therefore,as a potential source for exploring anti-diabetic leads,further investigation is warranted for Cornus officinalis.