| Curcuma kwangsiensis S.G.Lee et C.F.Ling, a perennial herbaceous plant of Zingiberaceae, is distributed in the southwest of China, especially in Guangxi, Yunnan, and Sichuan Province. The dried rhizomes of C. kwangsiensis, C. wenyujin and C. phaeocaulis as the source of a traditional Chinese medicine, Rhizoma Curcumae, were currently embodied in the Pharmacopoeia of the P. R. China (2010). C. kwangsiensis is an important herbal drug, which has used for treatment of stomach trouble, and "Oketsu", various syndromes caused by the obstruction of blood circulation, such as arthralgia, psychataxia, and dysmenorhea. Some literatures in pharmacology had reported that C. kwangsiensis possesses antitumor, antiviral, antioxidant, anti-inflammatory, and vasorelaxant activities. In recent years, some studies paid attention to its pharmacological activity and the extract of its volatile oil, but there were few literatures on the chemical constituents of C. kwangsiensis. Therefore, a systematic chemical research on the constituents of C. kwangsiensis was carried out, which resulted in the isolation of 55 compounds. The chemical structures of 55 compounds were determined on the basis of chemical and spectroscopic methods, including forty one diarylheptanoids: (3S)-1,7-bis(4-hydroxyphenyl)-(6E)-6-hepten-3-ol (1a)*, (3R)-1,7-bis(4-hydroxyphenyl)-(6E)-6-hepten-3-ol (1b)*, (3S)-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-(6E)-6-hepten-3-ol (2a)*, (3R)-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-(6E)-6-hepten-3-ol (2b)*, (3S)-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)heptan-3-ol (3a)*, (3R)-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl) heptan-3-ol (3b)*, (3S)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol (4a), (3R)-1-(3,4-dihydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-ol (4b)*, (3S)-3-acetoxy-l-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-(6E)-6-heptene (5a)*, (3R)-3-acetoxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-(6E)-6-heptene (5b)*, (3S)-3-acetoxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)heptane (6a)*, (3R)-3-acetoxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)heptane (6b)*, (E)-1,7-bis(4-hydroxyphenyl)-6-hepten-3-one (7)*, (3S,5S)-3-acetoxy-5-hydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxy-phenyl)heptane (8a)*, (3R,5R)-3-acetoxy-5-hydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)heptane (8b)*, (3R’,5S’)-3,5-dihydroxy-1-(3,4-dihydroxyphenyl)-7- (4-hydroxyphenyl)heptane (9)*, (3R’,5S’)-3,5-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)heptane (10)*,(3R’,5S’)-3,5-dihydroxy-1-(3-methoxy-4,5-dihydroxyphenyl)-7-(4-hydroxyphenyl)heptane (11)*, (3R,5R)-3-acetoxy-5-hydroxy-1,7-bis(4-hydroxyphenyl) heptane (12)*, (3R,5R)-3-acetoxy-5-hydroxy-1,7-bis(3,4-dihydroxyphenyl)heptane (13)*, (3R,5R)-3,5-diacetoxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)heptane (14)*,2,3,5-trihydroxy-1-(3-methoxy-4-hydroxyphenyl)-7-(3,5-dimethoxy-4-hydroxyphenyl)heptane (15) *,2,3,5-trihydroxy-1-(4-hydroxyphenyl)-7-(3,5-dimethoxy-4-hydroxyphenyl)heptane (16)*, 1,5-epoxy-3α-hydroxy-1-(3,4-dihydroxy-5-methoxyphenyl)-7-(3,4-dihydroxy)heptane (17), (5S)-5-hydroxy-1-(4-hydroxyphenyl)-7-(3,4-dihydroxyphenyl)-3-heptanone (18), (5S)-5-hydroxy-1-(4-hydroxyphenyl)-7-phenyl-3-heptanone (19), (5S)-5-hydroxy-3-platyphyllone (20), (5S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-3-heptanone (21), (5S)-5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3,4-dihydroxyphenyl)-3-heptanone (22),5-hydroxy-l-(4-hydroxyphenyl)-7-phenyl-hepta-6-en-3-one (23) 5-methoxy-l-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-3-heptanone (24) (3S,5S)-3,5-diacetoxy-1,7-bis(3,4-dihydroxyphenyl)heptane (25), (3R’,5S’)-3,5-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-7-(3,4-dihydroxyphenyl)heptane (26), (3R,5S)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (27), (3R,5R)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (28), 1-(4-hydroxyphenyl)-7-phenyl-(6E)-6-hepten-3-one (29), 1,7-bis(4-hydroxyphenyl)-3-heptanone (30),1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-3-heptanone (31), 1,7-bis(4-hydroxyphenyl)hepta-4E,6E-dien-3-one (32), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-(4E)-4-hepten-3-one (33), (3R,5R)-3,5-dihydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)heptane (34); four sesquiterpenes: 13-hydroxygermacrone (38), hydroxyatractylolide (39), Zedoarolide B (40), 13-hydroxygermacrone (41); two diterpenes:(E)-labda-8(17),12-diene-15-ol-16-al (36), galanolactone (37); six phenolic acid and phenolic ester derivatives:2,4,6-trihydroxyaceto phenone-2,4-di-O-β-D-glucopyranoside (35), nicotinic acid (44), (E)-3-(4-methoxyphenyl) acrylic acid (45), (E)-methyl-3-(4-hydroxy-3-methoxyphenyl)acrylate (46),3-methoxy-4-hydroxybenzaldehyde (47),4-hydroxybenzaldehyde (48); two nucleosides:uridine (42), adenosine (43). Twenty five diarylheptanoids were new compounds (1a, 1b,2a,2b,3a,3b, 4b,5a,5b,6a,6b,7,8a,8b,9—16,18,19,21), nine compounds (22,24,26,30,31,33,35, 36,37) were isolated for the first time from the plants of this genus. The investigation enriched the constituent-types of C. kwangsiensis and could provide material basis for further activity screening.Natural curcuminoids consist mainly of three diarylheptanoids:curcumin, demethoxycurcumin, and bisdemethoxycurcumin, extracted from the root of C. Longa L. and C. aromatica Salisb.. Curcuminoids have been used to treat and prevent cancer and other degenerative disorders in many countries and peoples, under the guidance of their traditional medicine theory, and they are one of some safe natural pigments suggested by the United Nations Food and Agriculture Organization (FAO) and World Health Organization (WHO). Some recent studies on the beneficial effects of curcuminoids shown that they posses broad spectrum of biological activities, in particular, its heptoprotective, anti-inflammatory, anti-HIV, antioxidant, and anticarcinogenic effects.Studies on the pharmacokinetic properties of curcuminoids in various animal species indicated that curcuminoids had low bioavailabilities, and were extensively metabolized in rats and human. Obviously, it is necessary for us to study the metabolic products of curcuminoids. Curcuminoids as natural yellow-orange pigments contain three diarylheptanoids:curcumin, demethoxycurcumin, and bisdemethoxycurcumin. Recently, information on the metabolism of curcumin, a major constituent of curcuminoids, had been obtained from in vitro studies with hepatic and intestinal cells and subcellular fractions, as well as from clinical studies in cancer patients. The metabolism of natural curcuminoids, as a mixture containing three diarylheptanoids, has not been fully characterized. Therefore, studies of the metabolic products of natural curcuminoids in urine and feces after oral administration in male Wistar rats were undertaken. And seven phase I reductive products were isolated. The metabolites were identified primarily on the basis of NMR techniques and MS studies, including hexahydrocurcumin (Ml), octahydrocurcumin (M2), hexahydro-demethoxy curcumin-A (M3), hexahydro-demethoxycurcumin-B (M4),5-hydroxy-3-platyphyllone (M5), 3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (M6),3-hydroxy-1,7-bis(4-hydroxyphenyl)heptane (M7). Natural curcuminoids in vivo follows almost the same pathway as curcumin and demethoxycurcumin:no oxidative metabolites were observed, and two patterns of biotransformation, reduction and dehydroxylation were demonstrated. At the same time, some metabolites were found in form of the enantiomeric mixtures, by means of a chiral column. These results are important for understanding the metabolic pathway of natural curcuminoids in rats, and would lay the foundation for elucidating the in vivo pharmacological forms of the orally dosed curcuminoids. |
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