Antioxidative Catechol Lignans Converted from Sesamin and Sesaminol Triglucoside by Culturing with <i>Aspergillus</i>

Miyake, Yoichi; Fukumoto, Syuichi; Okada, Masahisa; Sakaida, Kazuhiro; Nakamura, Yoshimasa; Osawa, Toshihiko

doi:10.1021/jf048743h

Cited by 94 publications

(66 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies demonstrated that sesamin is metabolized to sesamin dicatechol via sesamin monocatechol in rats (Nakai et al, 2003;Peñalvo et al, 2005;Liu et al, 2006). It is noted that sesamin dicatechol is a more potent antioxidant than sesamin monocatechol (Nakai et al, 2003;Miyake et al, 2005). Thus, the conversion from monocatechol to dicatechol is pharmacologically important.…”

Section: Metabolism Of Sesamin By Human P450mentioning

confidence: 99%

“…Liu et al (2006) proposed tentative metabolic pathways of sesamin. Among the 11 kinds of the metabolites, mono-and dicatechol metabolites, which appear to be metabolized by P450s, are known to have high antioxidative activities (Nakai et al, 2003;Miyake et al, 2005). It was reported that sesamin elevated CYP2B and CYP4A mRNA levels in rats (Tsuruoka et al, 2005;Ikeda et al, 2007) and CYP1A activity in rainbow trout (Trattner et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Metabolism of Sesamin by Cytochrome P450 in Human Liver Microsomes

Yasuda

Ikushiro²,

Kawamura³

et al. 2010

Drug Metab Dispos

View full text Add to dashboard Cite

ABSTRACT:Metabolism of sesamin by cytochrome P450 (P450) was examined using yeast expression system and human liver microsomes. Saccharomyces cerevisiae cells expressing each of human P450 isoforms (CYP1A1, 1A2, 2A6, 2B6, 2C8, 2C9, 2C18, 2C19, 2D6, 2E1, and 3A4) were cultivated with sesamin, and monocatechol metabolite was observed in most of P450s. Kinetic analysis using the microsomal fractions of the recombinant S. cerevisiae cells revealed that CYP2C19 had the largest k cat /K m value. Based on the kinetic data and average contents of the P450 isoforms in the human liver, the putative contribution of P450s for sesamin metabolism was large in the order of CYP2C9, 1A2, 2C19, and 2D6. A good correlation was observed between sesamin catecholization activity and CYP2C9-specific activity in in vitro studies using 10 individual human liver microsomes, strongly suggesting that CYP2C9 is the most important P450 isoform for sesamin catecholization in human liver. Inhibition studies using each anti-P450 isoform-specific antibody confirmed that CYP2C9 was the most important, and the secondary most important P450 was CYP1A2. We also examined the inhibitory effect of sesamin for P450 isoform-specific activities and found a mechanism-based inhibition of CYP2C9 by sesamin. In contrast, no mechanism-based inhibition by sesamin was observed in CYP1A2-specific activity. Our findings strongly suggest that further studies are needed to reveal the interaction between sesamin and therapeutic drugs mainly metabolized by CYP2C9.

show abstract

Section: Metabolism Of Sesamin By Human P450mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metabolism of Sesamin by Cytochrome P450 in Human Liver Microsomes

Yasuda

Ikushiro²,

Kawamura³

et al. 2010

Drug Metab Dispos

View full text Add to dashboard Cite

show abstract

“…They have the pharmacological properties including anti-inflammatory 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 effects [11], antioxidant activity [12], antihypertensive effects [13], apoptosis-induction in tumor cells [14], enhancing antioxidant activity of vitamin E [15], lowering cholesterol levels [16], improving fatty acid metabolism [17], and neuroprotective effects against hypoxia [18]. Recently, we reported that sesamin treatment in vitro reversed pathological changes in OA cartilage: reduced the disorganization of chondrocytes in cartilage, increased cartilage thickness and decreased losses of type II collagen and CS-PGs [11].…”

mentioning

confidence: 99%

Effects of sesamin on the biosynthesis of chondroitin sulfate proteoglycans in human articular chondrocytes in primary culture

et al. 2013

View full text Add to dashboard Cite

“…The frequency of the CYP2C19*17 allele is high (18%) in Ethiopians and Swedes (Sim et al, 2006), 0.64% in Chinese (Wang et al, 2009), and 1.3% in Japanese (Sugimoto et al, 2008). The antioxidant effects of episesamin in ultra-rapid metabolizers might be larger than those in normal metabolizers because of a high ability of dicatechol formation (Nakai et al, 2003;Miyake et al, 2005). However, CYP2C19 poor metabolizers, whose frequency is approximately 20% in Japanese and Koreans, appear to have a low ability to form episesamin dicatechol.…”

mentioning

confidence: 99%

Comparison of Metabolism of Sesamin and Episesamin by Drug-Metabolizing Enzymes in Human Liver

et al. 2012

View full text Add to dashboard Cite

ABSTRACT:Sesamin and episesamin are two epimeric lignans that are found in refined sesame oil. Commercially available sesamin supplements contain both sesamin and episesamin at an approximate 1:1 ratio. Our previous study clarified the sequential metabolism of sesamin by cytochrome P450 (P450) and UDP-glucuronosyltransferase in human liver. In addition, we revealed that sesamin caused a mechanism-based inhibition (MBI) of CYP2C9, the P450 enzyme responsible for sesamin monocatecholization. In the present study, we compared the metabolism and the MBI of episesamin with those of sesamin. Episesamin was first metabolized to the two epimers of monocatechol, S-and R-monocatechols in human liver microsomes. The P450 enzymes responsible for S-and R-monocatechol formation were CYP2C9 and CYP1A2, respectively. The contribution of CYP2C9 was much larger than that of CYP1A2 in sesamin metabolism, whereas the contribution of CYP2C9 was almost equal to that of CYP1A2 in episesamin metabolism. Docking of episesamin to the active site of CYP1A2 explained the stereoselectivity in CYP1A2-dependent episesamin monocatecholization. Similar to sesamin, the episesamin S-and R-monocatechols were further metabolized to dicatechol, glucuronide, and methylate metabolites in human liver; however, the contribution of each reaction was significantly different between sesamin and episesamin. The liver microsomes from CYP2C19 ultra-rapid metabolizers showed a significant amount of episesamin dicatechol. In this study, we have revealed significantly different metabolism by P450, UDPglucuronosyltransferase, and catechol-O-methyltransferase for sesamin and episesamin, resulting in different biological effects.

show abstract

Antioxidative Catechol Lignans Converted from Sesamin and Sesaminol Triglucoside by Culturing with Aspergillus

Cited by 94 publications

References 21 publications

Metabolism of Sesamin by Cytochrome P450 in Human Liver Microsomes

Metabolism of Sesamin by Cytochrome P450 in Human Liver Microsomes

Effects of sesamin on the biosynthesis of chondroitin sulfate proteoglycans in human articular chondrocytes in primary culture

Comparison of Metabolism of Sesamin and Episesamin by Drug-Metabolizing Enzymes in Human Liver

Contact Info

Product

Resources

About