Screening of Indigenous Plants from Japan for Modulating Effects on Transformation of the Aryl Hydrocarbon Receptor

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor with which halogenated and ‍polycyclic aromatic hydrocarbons such as dioxins and benzo[a]pyrene interact as ligands. Since such compounds ‍cause various toxicological effects, including cancer, through the transformation of AhR, it is important to determine ‍influence of modulating factors. It has been reported that certain plant components such as flavonoids and indoles ‍can affect AhR transformation. In this study, to obtain clues to novel ligands of AhR, 191 species of indigenous ‍plants were collected in Japan, and their 50% methanolic extracts (total 368 plant parts) were tested for modulating ‍effects on AhR transformation in a cell-free system using a rat hepatic cytosolic fraction. Among tested extracts at a ‍concentration of 1 mg dry weight of plant/mL, 174 of 368 extracts suppressed 1 nM 2,3,7,8-tetrachlorodibenzo-pdioxin ‍(TCDD)-induced AhR transformation to 50% or less, while 9 extracts per se induced AhR transformation ‍equivalent to more than 20% of that induced by 1 nM TCDD. Mallotus japonicus (Thunb.) Muell. (leaf) and ‍Trichosanthes rostrata Kitamura (fruit and fruit skin) strongly suppressed 1 nM TCDD-induced AhR transformation, ‍while Phellodendron amurense Ruprecht (seed) per se strongly induced AhR transformation. These results suggest ‍that a large variety of plants in Japan contain various compounds modulating, mainly suppressing, AhR ‍transformation.