In Vitro Effect of Standardized Ginseng Extracts and Individual Ginsenosides on the Catalytic Activity of Human CYP1A1, CYP1A2, and CYP1B1

Abstract

ABSTRACT:Ginseng extract has been reported to decrease the incidence of 7,12-dimethylbenz[a]anthracene (DMBA)-initiated tumorigenesis in mice. A potential mechanism for this effect by ginseng is inhibition of DMBA-bioactivating cytochrome P450 (P450) enzymes. In the present in vitro study, we examined the effect of a standardized Panax ginseng (or Asian ginseng) extract (G115), a standardized Panax quinquefolius (or North American ginseng) extract (NAGE), and individual ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1) on CYP1 catalytic activities, as assessed by 7-ethoxyresorufin O-dealkylation. G115 and NAGE decreased human recombinant CYP1A1, CYP1A2, and CYP1B1 activities in a concentration-dependent manner. Except for the competitive inhibition of CYP1A1 by G115, the mode of inhibition was the mixed-type in the other cases. A striking finding was that NAGE was 45-fold more potent than G115 in inhibiting CYP1A2. Compared with G115, NAGE also preferentially inhibited 7-ethoxyresorufin O-dealkylation activity in human liver microsomes. Rb1, Rb2, Rc, Rd, Re, Rf, and Rg1, either individually or as a mixture and at the levels reflecting those found in an inhibitory concentration (100 g/ml) of NAGE or G115, did not influence CYP1 activities. However, at a higher ginsenoside concentration (50 g/ml), Rb1, Rb2, Rc, Rd, and Rf inhibited these activities. Overall, our in vitro findings indicate that standardized NAGE and G115 extracts, which were not treated with calf serum or subjected to acid hydrolysis, inhibited CYP1 catalytic activity in an enzyme-selective and extract-specific manner, but the effects were not due to Rb1, Rb2, Rc, Rd, Re, Rf, or Rg1.Ginseng is one of the most commonly used herbal products by American consumers (Eliason et al., 1997;Harnack et al., 2001), and the annual sales of ginseng in the United States are more than $300 million (Gillis, 1997). Ginseng refers to the roots of species of the genus Panax. There are several species of ginseng (Soldati, 2000), including Panax ginseng C. A. Meyer (or Asian ginseng), which is mainly from Korea and Eastern China, and Panax quinquefolius L. (or North American ginseng), which is primarily from Wisconsin and British Columbia, Canada. To date, approximately 200 substances have been isolated and characterized from P. ginseng (Soldati, 2000). The characteristic markers of both species are the ginsenosides (Attele et al., 1999), which are steroidal saponins (Attele et al., 1999). Ginseng is used as a general body tonic, and it is touted to counteract fatigue, boost the immune system, improve physical stamina, and stimulate the appetite (Elias and Masline, 1995). The mechanism of action of ginseng is not known, but it is thought to have effects on learning, memory and behavior, cardiovascular function perhaps through mediation by nitric oxide, neuroendocrine function, carbohydrate and lipid metabolism, and immune function (Liu and Xiao, 1992).The oral administration of red ginseng extracts, which were produced by steam treatment of the roots of P. ginseng, was ...

Degradation of Ginsenosides in Humans After Oral Administration

“…2 shows all ginsenosides detected being G-Rg 1 , G-Rb 1 , G-Rb 2 /G-Rc, G-Rd, G-Re, and G-Rf. As known from previous analyses, G-Rb 1 , G-Rb 2 , and G-Rc represent quantitatively the main components of the protopanaxadiol ginsenosides in Ginsana G115 capsules, whereas G-Rg 1 and G-Re are the main components of the protopanaxatriol ginsenosides (Chang et al, 2002).…”

“…In a recent article, Chang et al (2002) studied the effect of standardized Panax ginseng extract (G115), standardized P. quinquefolius extract (NAGE) and individual ginsenosides (Rb 1 , Rb 2 , Rc, Rd, Re, Rf, and Rg 1 ) on cytochrome P450 catalytic activity in vitro. The findings indicate that standardized G115 and NAGE extracts decreased human recombinant CYP1A1, CYP1A2, and CYP1B1 activities in an enzyme-selective and extract-specific manner, whereas the isolated ginsenosides, either individually or as a mixture, did not influence the catalytic activity except at higher concentrations.…”

LACK OF EVIDENCE FOR INDUCTION OF CYP2B1, CYP3A23, AND CYP1A2 GENE EXPRESSION BY Panax ginseng AND Panax quinquefolius EXTRACTS IN ADULT RATS AND PRIMARY CULTURES OF RAT HEPATOCYTES

“…P. ginseng [G115, lot 1254/485; 4% (w/w) total ginsenosides] and P. quinquefolius extracts [lot AGSP110200; 10% (w/w) total ginsenosides] were provided by Pharmaton S.A. (Bioggio, Switzerland) and the Canadian Phytopharmaceuticals Corp. (Richmond, BC, Canada), respectively. The amounts of ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, and Rg2 present in the P. ginseng and P. quinquefolius extracts have been detailed elsewhere (Chang et al, 2002 Bio-Rad (Hercules, CA). The sources of the polymerase chain reaction (PCR) primers and the reagents for isolation of total RNA, reverse transcription, quantification of total RNA and total cDNA concentrations, and real-time PCR have been detailed elsewhere (Chang et al, 2003).…”

In Vitro Inhibition of Multiple Cytochrome P450 Isoforms by Xanthone Derivatives from Mangosteen Extract

“…The incidence of potential cytochrome P450 (P450)-mediated drug inhibition from herbal therapies has been noted for popular remedies such as St. John's wort, echinacea, ginseng, garlic, and saw palmetto (Obach, 2000;Foster et al, 2001;Chang et al, 2002;He and Edeki, 2004;Yale and Glurich, 2005;Liu et al, 2006;Modarai et al, 2007). Various herbal constituents have also been shown to induce P450 activity in vitro.…”