J Vet Sci.  2011 Jun;12(2):115-119. 10.4142/jvs.2011.12.2.115.

In vivo metabolism of Talosin A, new isoflavonol glycoside from Kitasatospora kifunensis, in rats

• Lim JH
• Song IB
• Hwang YH
• Kim MS
• Kim JW
• Kim JY
• Suh JW
• Yun HI

• KMID: 1106552
• DOI: http://doi.org/10.4142/jvs.2011.12.2.115

Abstract

The isoflavonol glycoside Talosin A, genistein (GT)-7-alpha-L-6-deoxy talopyranose (GT-Tal), was first isolated from the culture broth of Kitasatospora kifunensis MJM341. The aim of the present study was to evaluate the oral absorption and metabolism of the newly isolated isoflavonol glycoside, GT-Tal compared to genistin (GT-7-O-beta-D-glucopyranoside; GT-Glu). Free GT-Glu and GT-Tal could not be detected prior to enzymatic hydrolysis of the corresponding conjugates in rat plasma. Following oral administration of GT-Tal (15 min), GT-Tal was rapidly absorbed through the gastrointestinal tract and metabolized into GT-Tal conjugates with a mean Cmax of 2.74 microg/mL. GT-Tal was further metabolized to its aglycone, free GT and conjugated GT. After oral administration, GT-Glu was absorbed after being convereted to its aglycone and then further metabolized into its conjugate metabolites (free GT with a mean Cmax of 0.24 mg/mL at 1.25 h; conjugated GT with a mean Cmax of 1.31 mg/mL at 2.00 h). Significant differences in absorption and metabolism of GT-Tal and GT-Glu were observed. GT-Tal was metabolized into its corresponding conjugates or underwent deglycosylation to form GT, whereas GT-Glu was metabolized into its aglycone, GT.

Keyword

genistin; isoflavonol; metabolism; pharmacokinetics; Talosin A

MeSH Terms

Actinobacteria/*chemistry
Administration, Oral
Animals
Area Under Curve
Glycosides/administration & dosage/*metabolism/pharmacokinetics
Hydrolysis
Intestinal Absorption
Isoflavones/administration & dosage/*metabolism/pharmacokinetics
Male
Random Allocation
Rats
Rats, Sprague-Dawley

Figure

• 

  Fig. 1 Mean plasma concentration-time curves of genistein (GT) after an oral administration of 20 mg/kg GT-7-O-β-D-glucopyranoside (GT-Glu) in rats (n = 4). Filled circles (●): conjugated plasma GT, empty circles (○): free plasma GT. Free GT-Glu was not detected in rat plasma samples after oral administration of genistin. Data are expressed as mean ± SD.

• 

  Fig. 2 Mean plasma concentration-time curves of GT-7-α-L-6-deoxy talopyranose (GT-Tal) and GT after an oral administration of 20 mg/kg GT-Tal in rats (n = 4). Filled circles (●): plasma conjugated GT-Tal, empty circles (○): plasma conjugated GT, filled triangles (▼): free plasma GT. Free GT-Tal was not detected in rat plasma samples after oral administration of GT-Tal. Data are expressed as mean ± SD.

Reference

1. Andlauer W, Kolb J, Fürst P. Absorption and metabolism of genistin in the isolated rat small intestine. FEBS Lett. 2000. 475:127–130.

2. Clarke DB, Lloyd AS, Botting NP, Oldfield MF, Needs PW, Wiseman H. Measurement of intact sulfate and glucuronide phytoestrogen conjugates in human urine using isotope dilution liquid chromatography-tandem mass spectrometry with [¹³C₃]isoflavone internal standards. Anal Biochem. 2002. 309:158–172.

3. Day AJ, Cañada FJ, Díaz JC, Kroon PA, Mclauchlan R, Faulds CB, Plumb GW, Morgan MRA, Williamson G. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Lett. 2000. 468:166–170.

4. Doerge DR, Chang HC, Churchwell MI, Holder CL. Analysis of soy isoflavone conjugation in vitro and in human blood using liquid chromatography-mass spectrometry. Drug Metab Dispos. 2000. 28:298–307.

5. Hwang YH, Kim MS, Song IB, Lim JH, Park BK, Yun HI. Anti-inflammatory effects of talosin A via inhibition of NF-kappaB activation in lipopolysaccharide-stimulated RAW264.7 cells. Biotechnol Lett. 2009. 31:789–795.

6. Hollman PC, Bijsman MN, van Gameren Y, Cnossen EP, de Vries JH, Katan MB. The sugar moiety is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Radic Res. 1999. 31:569–573.

7. Kim WG, Yoon TM, Kwon HJ, Suh JW. Talosins A and B: new isoflavonol glycosides with potent antifungal activity from Kitasatospora kifunensis MJM341. II. Physicochemical properties and structure determination. J Antibiot (Tokyo). 2006. 59:640–645.

8. Knirel YA, Shashkov AS, Senchenkova SN, Merino S, Tomás JM. Structure of the O-polysaccharide of Aeromonas hydrophila O:34; a case of random O-acetylation of 6-deoxy-L-talose. Carbohydr Res. 2002. 337:1381–1386.

9. Kwon SH, Kang MJ, Huh JS, Ha KW, Lee JR, Lee SK, Lee BS, Han IH, Lee MS, Lee MW, Lee J, Choi YW. Comparison of oral bioavailability of genistein and genistin in rats. Int J Pharm. 2007. 337:148–154.

10. Miyadoh S. Research on antibiotic screening in Japan over the last decade: A producing microorganism approach. Actinomycetologica. 1993. 7:100–106.

11. Nielsen ILF, Williamson G. Review of the factors affecting bioavailability of soy isoflavones in humans. Nutr Cancer. 2007. 57:1–10.

12. Õmura S, Takahashi Y, Iwai Y, Tanaka H. Kitasatosporia, a new genus of the order Actinomycetales. J Antibiot (Tokyo). 1982. 35:1013–1019.

13. Perry MB, MacLean LM, Brisson JR, Wilson ME. Structures of the antigenic O-polysaccharides of lipopolysaccharides produced by Actinobacillus actinomycetemcomitans serotypes a, c, d and e. Eur J Biochem. 1996. 242:682–688.

14. Piskula MK, Yamakoshi J, Iwai Y. Daidzein and genistein but not their glucosides are absorbed from the rat stomach. FEBS Lett. 1999. 447:287–291.

15. Setchell KDR, Brown NM, Desai P, Zimmer-Nechemias L, Wolfe BE, Brashear WT, Kirschner AS, Cassidy A, Heubi JE. Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements. J Nutr. 2001. 131:4 Suppl. 1362S–1375S.

16. Spencer JPE, Chowrimootoo G, Choudhury R, Debnam ES, Srai SK, Rice-Evans C. The small intestine can both absorb and glucuronidate luminal flavonoids. FEBS Lett. 1999. 458:224–230.

17. Steensma A, Faassen-Peters MAW, Noteborn HPJM, Rietjens IMCM. Bioavailability of genistein and its glycoside genistin as measured in the portal vein of freely moving unanesthetized rats. J Agric Food Chem. 2006. 54:8006–8012.

18. Takahshi Y, Õmura S. Isolation of new actinomycete strains for the screening of new bioactive compounds. J Gen Appl Microbiol. 2003. 49:141–154.

19. Torgov VI, Shashkov AS, Kochanowski H, Jann B, Jann K. NMR analysis of the structure of the O88 polysaccharide (O88 antigen) of Escherichia coli O88:K^-:H25. Carbohydr Res. 1996. 283:223–227.

20. Walgren RA, Lin JT, Kinne RKH, Walle T. Cellular uptake of dietary flavonoid quercetin 4'-β-glucoside by sodium-dependent glucose transporter SGLT1. J Pharmacol Exp Ther. 2000. 294:837–843.

21. Walsh KR, Haak SJ, Bohn T, Tian Q, Schwartz SJ, Failla ML. Isoflavonoid glucosides are deconjugated and absorbed in the small intestine of human subjects with ileostomies. Am J Clin Nutr. 2007. 85:1050–1056.

22. Yoon TM, Kim JW, Kim JG, Kim WG, Suh JW. Talosins A and B: new isoflavonol glycosides with potent antifungal activity from Kitasatospora kifunensis MJM341. I. Taxonomy, fermentation, isolation, and biological activities. J Antibiot (Tokyo). 2006. 59:633–639.

23. Zhang Y, Song TT, Cunnick JE, Murphy PA, Hendrich S. Daidzein and genistein glucuronides in vitro are weakly estrogenic and activate human natural killer cells at nutritionally relevant concentrations. J Nutr. 1999. 129:399–405.

24. Zhou S, Hu Y, Zhang B, Teng Z, Gan H, Yang Z, Wang Q, Huan M, Mei Q. Dose-dependent absorption, metabolism, and excretion of genistein in rats. J Agric Food Chem. 2008. 56:8354–8359.