| Curcuma wenyujin,a perennial herbaceous plant of Zingiberaceae,is distributed in the south of China,especially in Zhejiang Province.In traditional Chinese and Japanese medicine, the rhizomes of Curcuma wenyujin are generally used to treat the Oketsu syndromes(various syndromes caused by the obstruction of blood circulation such as arthralgia and dysmenorrhea).The essential oil of Curcuma wenyujin is currently embodied in the Pharmacopoeia of the P.R.China(2005),as an anti-cancer and anti-virus remedy.Previous chemical investigations on the Curcuma wenyujin have led to the isolation of sesquiterpenoids and diarylheptanoids,some of these compounds possess significant vasorelaxant and hepatoprotective activities.In order to clarify the bioactive constituents of Curcuma wenyujin, the systematic investigation on the chemical constituents was carried out.As a result,43 compounds were isolated from the rhizomes of Curcuma wenyujin.On the basis of chemical evidences and spectral analysis,the structures of 40 compounds were elucidated as follows: sixteen guaiane-type sesquiterpenes:zedoalactone D(3),zedoalactone E(4),zedoalactone F(5),zedoalactone H(6),(1S,4S,5S,10R)-zedoarondiol(7),procurcumenol(14),zedoaron -diol(15),isozedoarondiol(16),zedoalactone A(17),zedoalactone B(18),zedoalactone C (19),aerugidiol(20),zedoarolide B(21),curcumenol(22),curcumol(23),and alismoxide (24);eight germacrane-type sesquiterpenes:curdionolide A(9),curdionolide B(10), curdionolide C(11),curdione(25),(4S,5S)-(+)-germacrone-4,5-epoxide(26), (1S,10S),(4S,5S)-(+)-germacrone- 1(10)-4-diepoxide(27),aeruginolactone(28),and(1E,4Z) -8-hydroxy-6-oxogermacra- 1(10),4,7(11)-trieno- 12,8-lactone(29);four eudesmane-type sesquiterpenes:curcodione(1),curcolide(2),1β,4α-dihydroxy-5α,8β(H)-eudesm-7(11) Z-en -12,8-olide(32),and curcolonol(33);two carabrane-type sesquiterpenes:curcumenone(30) and 4S-dihydrocurcumenone(31);one elemane-type sesquiterpene:hydroxyiso germafurenolide (34);one xanthane-type sesquiterpene:curcumadionol(12);one seco-germacrane -type sesquiterpene:6R-dehydroxylsipanolinolide(8);two diarylheptanoids:dicurcuminol (13),and 1,5-epoxy-3α-hydroxyl-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(4-hydroxy-3-meth -oxy-phenyl)heptane(35);two phenolic acid derivatives:ferulic acid(36),and p-hydroxy cinnamic acid(37);one flavonoid:5,7,4'-trihydroxy-flavanone(38);one sterol and its glycoside:daucosterol(39),andβ-sitosterol(40).Among them,Thirteen compounds(1-13) were new compounds,13 was a novel compound with new skeleton;11,a novel nitrogen-containing germacrane-type sesquiterpene,has been isolated from natural sources for the first time.Four compounds(29,32,35,38) were isolated for the first time from the plants of this genus.Six compounds(14.24,28,33,36,37) were isolated for the first time from the plants.The investigation enriched the constituent-types of C.wenyujin and could provide material basic for further activity screening.The inorganic free radical NO has been implicated in physiological and pathological processes,such as vasodilation,nonspecific host defense,ischemia reperfusion injury,and chronic or acute inflammation.NO is produced by the oxidation of L-arginine by NO synthase(NOS).In the NOS family,inducible NOS in particular is involved in a pathological aspect with overproduction of NO,and can be expressed in response to pro-inflammatory agents such as interleukin-1β,tumor necrosis factor-α,and LPS in various cells including macrophages,endothelial cells,and smooth muscle cells.In this thesis,we investigated the inhibitory effects of the 38 compounds on NO production in LPS-activated macrophages by Griess method.Among the tested compounds,6 sesquiterpenes(22,26,28,31,34 and 35) displayed potent inhibitory effects,compound 25 exhibited moderate activities,which were close to that of hydrocortisone.Compounds 1,5,29 and 32 showed very weak activities.And other compounds showed no activity.Curcumol is one of the representative index components in the quality standard of the essential oil which is currently used as an anti-cancer and anti-virus remedy,and embodied in the Pharmacopoeia of the P.R.China(2005).Recent studies suggested that the pharmacological activities of curcumol were consistent with those of the essential oil. Therefore,curcumol is one of the major bioactive components of the essential oil.Although a variety of biological activities have been reported for curcumol,there is so far only one research report on its metabolism.In order to characterize its biotransformation in mammalian animals,curcumol was orally administered in rats,and the urinary metabolites were investigated.Dr.Hui Zhang in our group previously isolated and identified 10 metabolites.In our continuous study,17 metabolites were isolated from the urine,and the structures of the 14 ones were elucidated as:10α,14,15-trihydroxy-(1αH,7βH)-guai-4-en-3,8-dione(M-1), 10α-hydroxy-(1αH,7βH,11βH)-guai-8(12),8(14)-diepoxy-4-en-3-one(M-2),10β-hydroxy-(1αH,7βH) -guai-4-en-3,8-dioxo- 12-oic acid(M-3),(1αH,7βH)-guai-4,10(14)-dien-3,8-dioxo -12-oic acid(M-4),5β,10β-dihydroxy-(1αH,7βH,11αH)-guai-8(12),8(14)-diepoxide(M-5), 5α,10β-dihydroxy-(1αH,7βH,11βH)-guai-8(12),8(14)-diepoxide(M-6),8β-hydroxy-(1αH,7βH,11βH)-guai-8(12)-epoxy-4,10(14)-dien-3-one(M-7),10β,14-dihydroxy curcumol(M-8), 5β,10β,14-trihydroxy-(1αH,7βH)-guai-8-one(M-9),10β-hydroxy-(1αH,7βH,11αH)-guai-8 (12),8(14)-diepoxy-4-en-3-one(M-10),10β-hydroxy-(1αH,7βH,11βH)-guai-8(12),8(14)-diepoxy -4-en-3-one(M-11),10α-hydroxy-(1αH,7βH,11αH)-guai-8(12),8(14)-diepoxy-4-en-3 -one(M-12),10β,14-dihydroxy-(1αH,7βH)-guai-4-en-3,8-dione(M-13),10α,14-dihydroxy -(1αH,7βH)-guai-4-en-3,8-dione(M-14),respectively.All the metabolites are phase 1 metabolites,and nine metabolites are new compounds(M-1-M-9),among which M-2,M-10, M-11,and M-12;M-13 and M-14;M-5 and M-6 are three pairs of epimeric metabolites. Based on the identified metabolites,we could find that hydroxylation,epoxidation,alcohol oxidation,dehydration,ketalization and epoxy-ring opening reaction are the main phase 1 metabolic passways of curcumol in rats.The study on the metabolism of curcumol in rats would clarify its metabolic pathway and metabolic rules,and provide the important information for its development and further investigation.
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