Role of phase 2 drug-metabolizing enzymes modulated by extracts from 78 herbal medicines in detoxification of electrophiles and lung cancer chemotherapy

• Published in: Journal of Traditional Medicines Vol. 27; no. 3; pp. 122 - 133
• Main Authors: Ohnuma, Tomokazu, Matsumoto, Takashi, Komatsu, Takao, Nishiyama, Takahito, Ogura, Kenichiro, Iwata, Hiroshi, Hiratsuka, Akira
• Format: Journal Article
• Language: English
• Published: Medical and Pharmaceutical Society for WAKAN-YAKU 2010
• Subjects: glutathione S-transferase; herbal medicine; NAD(P)H:quinone oxidoreductase 1; Nrf2; phase 2 drug-metabolizing enzyme
• ISSN: 1880-1447; 1881-3747
• DOI: 10.11339/jtm.27.122

Phase 2 drug-metabolizing enzymes (DMEs), such as glutathione S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1), play a major role in the cellular detoxification of pharmaceutical agents and carcinogens. Previously, we reported the inhibitory effects of human liver microsomal cytochrome P450 3A4 and 2D6, phase 1 DMEs, by extracts from 78 herbal medicines. In the present study, we investigated whether phase 2 DME activity in mammalian cells was affected by the herbal extracts. Among the herbal extracts tested, GST and NQO1 activities in Clone 9 cells, a cultured cell line from normal rat liver, were increased more than 1.5-fold by treatment with Incised Notopterygium Rhizome, Magnolia Bark, Saussurea Root, and Magnolia Flower extracts. On the other hand, both of those activities were decreased to less than one-fifth by treatment with Cassia Bark and Rhubarb extracts. Pretreatment of Clone 9 cells with the former four extracts that induced phase 2 DMEs resulted in protection against the cytotoxicities of the electrophiles menadione and 1-chloro-2,4-dinitrobenzene. In contrast, GST and NQO1 activities in human lung cancer A549 cells, which are known to have a high metabolism and show resistance to anticancer drugs, was significantly decreased by treatment with the Cassia Bark extract. These results suggest that phase 2 DME activity may be modulated by herbal medicines, and the modulation of phase 2 DMEs by herbal medicines might affect the action of concomitant drugs and the detoxification of carcinogens.