Hydrolysis is the dominating in vivo metabolism pathway for arctigenin: identification of novel metabolites of arctigenin by LC/MS/MS after oral administration in rats.

Abstract

The phenylpropanoid dibenzylbutyrolactone lignan arctigenin, a key component found in Arctium lappa, or burdock, has been reported with a variety of therapeutic effects including anticancer, anti-inflammation, and antivirus effects. Using LC/MS/MS, three novel metabolites of arctigenin, namely, arctigenic acid, arctigenin-4-O'-glucuronide, and 4-O-demethylarctigenin were identified after oral administration of arctigenin in rats for the first time. Another potential metabolite of arctigenin, arctigenin-4'-O-sulfate, was identified in vitro but not in vivo. Structure of arctigenic acid, the major metabolite of arctigenin, was confirmed by 13C-NMR and 1H-NMR. Rapid hydrolysis in plasma was identified as the major metabolic pathway of arctigenin after its oral administration, with Vmax, Km, and Clint in rat plasma determined to be 2.21 ± 0.12 nmol/min/mg, 89.12 ± 9.44 µM, and 24.74 µL/min/mg, respectively. Paraoxonase 1 was further confirmed to be the enzyme responsible for arctigenin hydrolysis, with Vmax, Km, and Clint determined to be 55.39 ± 1.49 nmol/min/mg, 300.3 ± 10.86 µM, and 184.45 µL/min/mg, respectively.

• Authors: Qiong Gao, Yufeng Zhang, Siukwan Wo, Zhong Zuo
• Journal: Planta medica (Planta Med) Vol. 79 Issue 6 Pg. 471-9 (Apr 2013) ISSN: 1439-0221 [Electronic] Germany
• PMID: 23519790 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• Furans
• Lignans
• arctigenic acid
• arctigenin

Topics

• Administration, Oral
• Animals
• Chromatography, Liquid
• Furans (chemistry, metabolism)
• Hydrolysis
• Kinetics
• Lignans (chemistry, metabolism)
• Nuclear Magnetic Resonance, Biomolecular
• Plasma (chemistry, metabolism)
• Rats
• Tandem Mass Spectrometry