Effects of aqueous extract of Ruta graveolens and its ingredients on cytochrome P450, uridine diphosphate (UDP)-glucuronosyltransferase, and reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H)-quinone oxidoreductase in mice

Yune-Fang Ueng; Chien-Chih Chen; Yu-Ling Huang; I-Jung Lee; Chul-Ho Yun; Yu-Hsuan Chen; Chiung-Chiao Huang

doi:10.1016/j.jfda.2015.03.005

Effects of aqueous extract of Ruta graveolens and its ingredients on cytochrome P450, uridine diphosphate (UDP)-glucuronosyltransferase, and reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H)-quinone oxidoreductase in mice

J Food Drug Anal. 2015 Sep;23(3):516-528. doi: 10.1016/j.jfda.2015.03.005. Epub 2015 May 21.

Authors

Yune-Fang Ueng¹, Chien-Chih Chen², Yu-Ling Huang³, I-Jung Lee⁴, Chul-Ho Yun⁵, Yu-Hsuan Chen⁶, Chiung-Chiao Huang⁶

Affiliations

¹ Division of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Taipei, Taiwan; Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan. Electronic address: ueng@nricm.edu.tw.
² Division of Chinese Medicinal Chemistry, National Research Institute of Chinese Medicine, Taipei, Taiwan; Department of Biotechnology, Hungkuang University, Taichung County, Taiwan; Department of Nursing, Hungkuang University, Taichung County, Taiwan.
³ Division of Chinese Medicinal Chemistry, National Research Institute of Chinese Medicine, Taipei, Taiwan; Department of Cosmetic Science, Chang Gung University of Science and Technology, Taoyuan County, Taiwan.
⁴ Division of Chinese Materia Medica Development, National Research Institute of Chinese Medicine, Taipei, Taiwan.
⁵ School of Biological Sciences and Technology, Chonnam National University, Gwangju, South Korea.
⁶ Division of Basic Chinese Medicine, National Research Institute of Chinese Medicine, Taipei, Taiwan.

Abstract

Ruta graveolens (the common rue) has been used for various therapeutic purposes, including relief of rheumatism and treatment of circulatory disorder. To elucidate the effects of rue on main drug-metabolizing enzymes, effects of an aqueous extract of the aerial part of rue and its ingredients on cytochrome P450 (P450/CYP), uridine diphosphate (UDP)-glucuronosyltransferase, and reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H):quinone oxidoreductase were studied in C57BL/6JNarl mice. Oral administration of rue extract to males increased hepatic Cyp1a and Cyp2b activities in a dose-dependent manner. Under a 7-day treatment regimen, rue extract (0.5 g/kg) induced hepatic Cyp1a and Cyp2b activities and protein levels in males and females. This treatment increased hepatic UDP-glucuronosyltransferase activity only in males. However, NAD(P)H:quinone oxidoreductase activity remained unchanged. Based on the contents of rutin and furanocoumarins of mouse dose of rue extract, rutin increased hepatic Cyp1a activity and the mixture of furanocoumarins (F_mix) increased Cyp2b activities in males. The mixture of rutin and F_mix increased Cyp1a and Cyp2b activities. These results revealed that rutin and F_mix contributed at least in part to the P450 induction by rue.

Keywords: Ruta graveolens; UDP-glucuronosyltransferase; cytochrome P450; furanocoumarins; rutin.

Grants and funding

This work was supported mainly by grants from the National Science Council, Taipei, Taiwan (grant numbers: NSC97-2320-B-077-009-MY3 and NSC101-2320-B-077-001-MY3) and partially by the National Research Institute of Chinese Medicine.