Inhibition of the initiation stage of carcinogenesis by Salvia disermas constituents.

Phytochemical studies of an ethanolic extract of the aerial parts of Salvia disermas resulted in the isolation of seven known compounds, rosmarinic (1) and caffeic (2) acids, salvigenin (3), luteolin (4), luteolin 7-O-beta-arabinoside (5), luteolin 7-O-beta-glucoside (6), and ocotillol II (7). The initiation stage of carcinogenesis is triggered by activation of procarcinogens by phase I enzymes, such as cytochrome P-450 1A, and oxidative stress that leads to DNA damage. The initiation stage is countered by phase II detoxification enzymes such as glutathione S-transferases (GST), quinine reductase (QR), epoxide hydrolase (mEH) besides conjugation with thiols. We aimed to investigate the cancer chemopreventive and tumour anti-initiating activity of the ethanolic extract of the aerial parts of Salvia disermas and its constituents. The S. disermas extract was a promising inhibitor of CYP1A activity, inducer of GST, QR, and mEH activities, enhancer of thiol content, radical scavenger, and inhibitor of DNA damage. On the other hand, 3 was an enhancer of thiol content and QR activity, while 4 was an inhibitor of CYP1A activity, inducer of QR activity, and radical scavenger of ROO*, and 5 was an inducer of GST activity and inhibitor of DNA damage. The present study indicated that the ethanolic extract of S. disermas and 4 are promising anti-initiating and multipotent blocking agents.