Plasma Pharmacokinetics and Tissue Distribution of Arctiin and Its Main Metabolite in Rats by HPLC-UV and LC-MS

Abstract

The pharmacokinetic profile of arctiin, the major active lignan in fruits of Arctium lappa L., was investigated. Its main meta“bolite arctigenin was identified by an LC-MS method, and an HPLC-UV technique was developed for the simultaneous quantification of the metabolite and arctiin in plasma and organs. Chromatographic separation was performed on an Agilent™ C₁₈ HPLC column with acetonitrile and water by linear gradient elution. Arctiin and arctigenin were identified on-line by LC-MS. The pharmacokinetics and tissue distribution of arctiin and arctigenin were determined for the first time by using a simple, selective, and accurate HPLC method. The AUC_0-t values of arctigenin were larger compared with arctiin after oral administration of arctiin. The concentration of the metabolite was significantly higher than the concentration of arctiin in the stomach and small intestine in rats after oral administration of arctiin, indicating that the stomach and small intestine were the major organs of arctiin metabolism. These findings could provide support for the clinical studies conducted with Fructus Arctii.

Key words

arctiin - arctigenin - HPLC-MS - pharmacokinetics - tissue distribution - Arctium lappa - Compositae

• References

• 1 Yan LX, Li YM. Effects of extract from Arctium lappa on the immunology and blood glucose in rats. NW Pharm J 1993; 8: 79
• 2 Lwakami S, Wu JB, Ebizuka Y, Sankawa U. Platelet activating factor (PAF) antagonists contained in medicinal plant: lignan and sesquiterpenes. Chem Pharm Bull 1992; 40: 1196
• 3 Fujimoto T, Nose M, Takeda T. Study on Chinese crude drug “Luoshiteng” (II) On the biological active components in the stem part of Luoshiteng originating from Trachelosperm jasminoides . Jpn J Phamacol 1992; 46: 224
• 4 Xie LH, Ahn EM, Akao T, Abdel-Hafez AA, Nakamura N, Hattori M. Transformation of arctiin to estrogenic and antiestrogenic substances by human intestinal bacteria. Chem Pharm Bull 2003; 51: 378-384
• 5 Takasaki M, Konoshima T, Komatsu K, Tokuda H, Nishino H. Anti-tumor-promoting activity of lignans from the aerial part of Saussurea medusa . Cancer Lett 2000; 158: 53-59
• 6 Hirose M, Yamaguchi T, Lin C, Kimoto N, Futakuchi M, Konoc T, Nishibed S, Shirai T. Effects of arctiin on PhiP-induced mammary, colon and pancreatic carcinogenesis in female Sprague-Dawley rats and MelQx-induced hepatocarcinogenesis in male F344 rats. Cancer Lett 2000; 155: 79-88
• 7 Hasumura M, Ueda M, Onose J, Imai T, Hirose M. Lack of a significant effect of arctiin on development of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in ovariectomized Sprague-Dawley rats. Nutr Cancer 2007; 57: 201-208
• 8 Sun WJ, Sha ZF, Gao H. Determination of arctiin and arctigenin in Fructus Arctii by reverse-phase HPLC. Yao Xue Xue Bao 1992; 27: 549-551
• 9 Liu H, Zhang Y, Sun Y, Wang X, Zhai Y, Sun Y, Sun S, Yu A, Zhang H, Wang Y. Determination of the major constituents in fruit of Arctium lappa L. by matrix solid-phase dispersion extraction coupled with HPLC separation and fluorescence detection. J Chromatogr B Anal Technol Biomed 2010; 878: 2707-2711
• 10 Liu S, Chen K, Schliemann W, Strack D. Isolation and identification of arctiin and arctigenin in leaves of burdock (Arctium lappa L.) by polyamide column chromatography in combination with HPLC-ESI/MS. Phytochem Anal 2005; 16: 86-89
• 11 Boldizsár I, Füzfai Z, Tóth F, Sedlák E, Borsodi L, Molnár-Perl I. Mass fragmentation study of the trimethylsilyl derivatives of arctiin, matairesinoside, arctigenin, phylligenin, matairesinol, pinoresinol and methylarctigenin: their gas and liquid chromatographic analysis in plant extracts. J Chromatogr A 2010; 1217: 1674-1682
• 12 Piaz FD, Imparato S, Lepore L, Bader A, Tommasi ND. A fast and efficient LC-MS/MS method for detection, identification and quantitative analysis of bioactive sesterterpenes in Salvia dominica crude extracts. J Pharm Biomed Anal 2010; 51: 70-77
• 13 Wang HY, Yang JS. Studies on the chemical constituents of Arctium lappa L. Yao Xue Xue Bao 1993; 28: 911-917
• 14 Nose M, Fujimoto T, Nishibe S, Ogihara Y. Structural transformation of lignan compounds in rat gastrointestinal tract; II. Serum concentration of lignans and their metabolites. Planta Med 1993; 59: 131-134
• 15 Jin JS, Zhao YF, Nakamura N, Akao T, Kakiuchi N, Hattori M. Isolation and characterization of a human intestinal bacterium, Eubacterium sp. ARC-2, capable of demethylating arctigenin, in the essential metabolic process to enterolactone. Biol Pharm Bull 2007; 30: 904-911