| The rhizomes of Curcuma Longa, a tropical herb indigenous to southern Asia, has played an important role in the pharmaceutical, food and textile industries in China, Japan and southeastern Asia for thousands of years. It has been widely used as an aromatic stomachic, carminative, anthelmintic, laxative, and as condiments in foods as well as for liver ailment. With regard to the chemical constituents of this plant, essential oil and curcuminoids were shown to be the major active principles, and the content of bisabolane type sesquiterpenes in volatile oil is high. Curcuminoids, consist mainly of three diarylheptanoids: curcumin, demethoxycurcumin, and bisdemethoxycurcumin. These are recognized for their beneficial effects such as a choleretic, as anti-oxidant, anti-inflammatory agents, for treating human immunodeficiency virus infections and as anticarcinogens. In recent years, their ability to protect neuronal cells fromβA insult has also attracted great attention. Demethoxycurcumnin was found to be the more effective in protecting PC12 and HUVEC cells fromβA insult than curcumin. Bisabolane-type sesquiterpenes have been reported to show antitumor, antifungal, anti-bacteria, antioxidant and antivenom effects. Although great attentions have been paid to the chemical and pharmacological research of curcumin, demethoxycurcumin and bisdemethoxycurcumin, there was little information on the other constituents of C. longa. Therefore, a systematic chemical research on the constituents of C. longa was carried out, which resulted in the isolation of 37 compounds. The chemical structures of 36 compounds were identified by spectral methods, including one bisabolane dirivate: (bisabola 4’-methyl-4’,10’-diene-9’-one-3’-yl)-(bisabola 4"-methyl-1",4"-dihydroxy-5",10"-diene-9"-one- 3"-yl)-methane (1); four isobisabolane-type compounds: isobisabolone A (2), isobisabolone B (3), isobisabolone C (4), isobisabolone D (5); nine bisabolane-type compounds: turmerone A (6), turmerone B (7), turmerone C (8), turmerone D (9), turmerune E (10), turmeronol B (11), bisabolone(12), bisabolone-9-one(13), turmeronol A(14): nine diarylheptanoids:(E)-1-(1,2-dihydro-6-hydroxyinden-3-ylidene)-4-(4-hydroxyphenyl)butan-2.one (15), (4E,6E)-2,5-epoxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (16), (1S)-1,5-epoxy-1-(3-methoxy-4-hydroxyphenyl)-7-(4-hydroxyphenyl)-4,6-heptadien-3-one (17), (1S)-1,5-epoxy-1-(4-hydroxylphenyl)-7-(3-methoxy-4-hydroxyphenyl)-4,6-heptadien-3-one (18), (1E,4E,6E)1-(3-methoxy-4-hydroxyphenyl)-7-(4-hydroxylphenyl)-1,4,6-heptatrien-3-one (19), 1,7-bis(4- hydroxyphenyl)-3-hydroxy-1,3-heptadien-5-one (20), curcumin (21), demethoxycurcumin (22),bisdemethoxycurcumin (23); two calebin derivatives: 4"-(3"’-methoxy-4"’-hydroxyphenyl)-2"-oxo-3"-butenyl-3-(4’-hydroxylphenyl)-propenoate (24)、4"-(4"-hydroxyphenyl)-2"-oxo-3"-butenyl-3-(3’-methoxy-4’-hydroxyphenyl)-propenoate (25); one diarylpentanoid constituent: 1-(4-hydroxy-3-methoxyphenyl)-5-(4-hydroxyphenyl)-(1E,4E)-pentadiene-3-one (26); nine phenolic acid derivatives: 4-hydroxy-3-methoxy cinnamaldehyde (27), ferulic acid methyl ester (28), 4-hydroxycinnamic acid methyl ester (29), 4-hydroxybenzaldehyde (30), 4-hydroxycinnamic acid (31), formylferulic acid (32), 4-hydroxy-cinnamaldehyde (33), vanillin (34), trans-ferulic acid (35) and one sterol compound: sitosterol(36). Among them 1 was novel compounds with new skeleton; 2-4 were isobisabolane-type sesquiterpenes discovered for the first time; 6-8, 15-19 and 24 were new compounds; 5 was a new artifact; 9 and 25 were new natural products; 13 and 27-31were isolated for the first time from the plants of this genus.The investigation enriched the constituent-types of C. longa and could provide material basic for further activity screening.Although numerous aspects of the pharmacology of curcuminoids, in particular its activity as chemopreventive agent, have been studied, the metabolism in humans and experimental animals have not been fully characterized. The metabolism of curcumin has mostly been studied in rats in vivo and in vitro. More recently, information on the metabolism of curcumin in humans has been obtained from in vitro studies with hepatic and intestinal cells and subcellular fractions, as well as from clinical studies with cancer patients. The metabolism of demethoxycurcumin, which is the major active component in curcuminoids such as curcumin, has only been studied on one report. In that investigation, in vitro studies with tissue slices and subcellular fractions from rat fiver were reported. No data have yet been published on the metabolism of demethoxycurcumin in vivo. Therefore, studies of the metabolic products of demethoxycurcumin in feces and urine after oral administration in male Wistar rats were undertaken. And nine phaseⅠreductive products were isolated. Four new metabolites: 5-dehydroxy-hexahydro-demethoxycurcumin-A (M-1), 5-dehydroxy-hexahydro-demethoxycurcumin -B (M-2), 5-dehydroxy-octahydro--demethoxycurcumin-A (M-3) and 5-dehydroxy-octahydrodemethoxycurcumin-B (M-4) were isolated from the feces, and three new metabolites: 5-O-methylhexahydro-demethoxycurcumin-A (M-7), 5-O-methyl-hexahydro-demethoxycurcumin-B (M-8), and 5-dehydroxy-dihydro-demethoxycurcumin-B(M-9) in addition to two known metabolites: hexahydro-demethoxycurcumin-A(M-5), hexahydro-demethoxycurcumin-B (M-6) from the urine of male Wistar rats. Their structures were established by spectral methods.Demethoxycurcumin in vivo follows almost the same pathway as curcumin and demethoxycurcumin in vitro: no oxidative metabolites were observed, and the reduction pattern of hydrogenation was about the same. However, there were two new discoveries in the present study: first the existence of the dehydroxy or methylated metabolites was demonstrated and secondly the existence of the isomers with a methoxy group substituted on a different benzene ring. These results are important for the understanding of demethoxycurcumin metabolism in rats and should provide information and reference for the further metabolic investigation of demethoxycurcumin in humans. |
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