Isolation of caffeic acid from Perilla frutescens and its role in enhancing γ-glutamylcysteine synthetase activity and glutathione level

Perilla frutescens is an annual herbaceous plant native to Asia, where its leaves are used in Asian gourmet food. Our previous study showed that the inhibition of γ-glutamylcysteine synthetase (γ-GCS) activity was remarkably recovered by pretreatment with perilla leaf extract (PLE). The objective was to fractionise PLE, and to identify the active component that is responsible for the enhancement of γ-GCS activity and glutathione (GSH) concentration. Among the five fractions from PLE, PLE-III of the ethyl acetate fraction showed the highest γ-GCS activity in a HepG2 cell experiment, and was further chromatographed. The purified compound, which enhanced γ-GCS activity, was finally identified as caffeic acid. We first report the enhancement of γ-GCS activity and GSH level in HepG2 cells by caffeic acid obtained from PLE. Our results suggest that caffeic acid may be a key factor in the chemopreventive potential of perilla leaf components by increasing de novo synthesis of GSH.