Chemoprevention of Lung Carcinogenesis by Red Ginseng and Ginsenoside Rg3 in A/J mice

Background: Red ginseng has long been used as a traditional medicine for a variety of maladies. Ginsenosides are the active components of ginseng but are limited by their low oral bioavailability. Methods: We evaluated several types of red ginseng extracts for their ability to inhibit lung tumor formation and growth induced by the carcinogen benzo(a)pyrene [B(a)P] in A/J mice. The concentrations of various ginsenosides were quantified in these ginseng extracts using the methods of ultra-performance liquid chromatography tandem mass spectrometry analysis to identify the ginsenosides that may contribute to cancer prevention. We next explored whether inhibition of P-glycoprotein by verapamil could increase the oral bioavailability of ginsenoside by using CaCo-2 cell transcellular transport and in situ mouse intestinal perfusion models. The plasma and intestine concentration of ginsenoside and cancer preventive effect of ginsenoside combined with verapamil in A/J mice were also detected by using B(a)P-induced mouse cancer model.Results: We found that treatment with one type of red ginseng (Korean red ginseng B, KRGB) led to a significant reduction of tumor load compared with other types of red ginseng. KRGB contained the highest concentration of ginsenoside Rg3 among these red ginseng extracts, suggested that Rg3 may play an important role in its preventive efficacy. Our study showed that Rg3 had a relatively poor bioavailability, and co-administration of verapamil decreased the efflux ratio of Rg3 in Caco-2 cells, increased the absorption rate of Rg3 in rat small intestine, increased the plasma and intestine concentration of Rg3 in A/J mice, and enhanced the cancer preventive effect of Rg3 against B(a)P induced lung tumorigenesis. Conclusions: Ginsenosides Rg3 is one of the key components of read ginseng that may be responsible for its efficacy against lung carcinogenesis in mice. Rg3 appears to be the substrate of P-glycoprotein, and inhibition of P-glycoprotein could enhance its oral bioavailability.