Isolation and Identification of Phase 1 Metabolites of Demethoxycurcumin in Rats

Abstract

ABSTRACT:Curcuminoids are a safe natural food coloring additive with antiinflammatory, antioxidant, and anticarcinogenic activities. Although demethoxycurcumin is one of the major bioactive constituents of curcuminoids, knowledge about its metabolic fate is scant. In the present study, four new metabolites, 5-dehydroxyhexahydro-demethoxycurcumin-A (M- Curcuminoids are natural yellow pigments and food-coloring agents present in the rhizomes of the Asian tropical plant Curcuma longa, which has been used as a traditional medicinal herb for thousands of years. The dried rhizome of C. longa has been widely used as an aromatic stomachic, carminative, anthelmintic, laxative, as well as for liver ailments and as condiments in foods (Nurfina et al., 1997). Curcuminoids are responsible for its biological actions. Curcuminoids consist mainly of three diarylheptanoids: curcumin, demethoxycurcumin, and bisdemethoxycurcumin (Govindaajan et al., 1980) (Fig. 1). These are recognized for their beneficial effects such as a choleretic (Ramprasad et al., 1956;Ammon and Martin, 1991), as antioxidants (Sharma, 1976;Unnikrishnan et al., 1995), anti-inflammatory agents (Arora et al., 1971;Ghatak et al., 1972), for treating human immunodeficiency virus infections (Mazumder et al., 1995;Eigner et al., 1999), and as anticarcinogens (Kuttan et al., 1985;Conney et al., 1991; Araujo et al., 2001;Duvoix et al., 2005). In recent years, their ability to protect neuronal cells from ␤A insult (Kim et al., 2001;Park et al., 2002) has also attracted great attention. Demethoxycurcumin was found to be more effective in protecting PC12 and human umbilical vein endothelial cells from ␤A insult than curcumin. Although numerous aspects of the pharmacology of curcuminoids, in particular their activity as a chemopreventive agent, have been studied, their metabolism in humans and experimental animals has not been fully characterized. The metabolism of curcumin has been studied mostly in rats in vivo and in vitro (Holder et al., 1978; Ravindranath et al., 1982; Asai et al., 1999; Pan et al., 2000;Ireson et al., 2001Ireson et al., , 2002. 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 (Ireson et al., , 2002, as well as from clinical studies in cancer patients (Cheng et al., 2001;Sharma et al., 2001Sharma et al., , 2004Garcea et al., 2004). 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 liver were reported (Hoehle et al., 2006). 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 p.o. administration in male Wistar rats were undertaken. The isolation and identification of nine phase 1 reductive metabolites of demethoxycurcumin are descr...

Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development

“…Zeng et al (2007) [1425] recently identified seven new metabolites of demethoxycurcumin, 5-dehydroxy-hexahydro-demethoxycurcumin (M1), 5-dehydroxy-hexahydro-demethoxycurcumin (M2), 5-dehydroxyoctahydro-demethoxycurcumin (M3) and 5-dehydroxy-octahydrodemethoxycurcumin (M4), 5-O-methyl-hexahydro-demethoxycurcumin (M7), 5-O-methyl-hexahydro-demethoxycurcumin-B (M8), and 5-dehydroxy-dihydro-demethoxycurcumin-B (M9), from feces of rats and from urine (Fig. (185) & Fig.…”

Metabolism of Echinacoside, a Good Antioxidant, in Rats: Isolation and Identification of Its Biliary Metabolites

“…In recent years, new techniques were applied to identify and characterize the metabolites, such as gas chromatography-MS, LC-MS (Rüfer et al, 2006;Xu et al, 2006), LC/NMR (Mutlib and Shockcor, 2003), NMR (Zhang et al, 2004;Zeng et al, 2007), and stable isotopes. In our study, three groups of positional isomers (M5, M6, M7, and M8; M1 and M2; and M3 and M4) were obtained.…”

Biotransformation of food spice curcumin by gut bacterium Bacillus megaterium DCMB-002 and its pharmacological implications

“…Based on this, a hypothesis was raised that the degradation or biotransformation products of CUR may make important contributions to its diverse bioactivities [5,7,8]. One of the supporting evidences was that the detected concentration of parent CUR molecule in human circulatory system was much lower than that in human intestinal tracts [9,10]. Additionally, many CUR analogues were also found in human or rat hepatocytes, plasma, and brain, indicative of some CUR structural transformation while assimilated from gut to blood [11,12].…”