Pharmacokinetic interactions between 20(S)-ginsenoside Rh2 and the HIV protease inhibitor ritonavir in vitro and in vivo

Journal of Ginseng Research

Min

2016

Korean Red Ginseng (KRG) is a heat-processed ginseng developed by the repeated steaming and air-drying of fresh ginseng. Compared with fresh ginseng, KRG has been shown to possess greater pharmacological activities and stability because of changes that occur in its chemical constituents during the steaming process. In addition to anticancer, anti-inflammatory, and immune-modulatory activities, KRG and its purified components have also been shown to possess protective effects against microbial infections. Here, we summarize the current knowledge on the properties of KRG and its components on infections with human pathogenic viruses such as respiratory syncytial virus, rhinovirus, influenza virus, human immunodeficiency virus, human herpes virus, hepatitis virus, norovirus, rotavirus, enterovirus, and coxsackievirus. Additionally, the therapeutic potential of KRG as an antiviral and vaccine adjuvant is discussed.

Section: Human Immunodeficiency Virusmentioning

confidence: 99%

Ginseng, the natural effectual antiviral: Protective effects of Korean Red Ginseng against viral infection

Journal of Ginseng Research

Min

2016

“…The rare ginsenosides 20(S)-Rh2, Rk2, and Rh3 have remarkable anti-cancer effects on various types of cancers [9,15], similar to that of ginsenoside C-K. In particular, the efficacy of 20(S)-Rh2, including anti-cancer, antihyperglycemic, and anti-obesity effects [26], has been reported in many previous publications. However, the production of high-purity ginsenoside Rh2 or its analogs (Rk2, Rh3) has been limited by a lack of ginsenoside transformation technology.…”

Section: Discussionmentioning

confidence: 81%

Production of the Rare Ginsenoside Rh2-MIX (20(S)-Rh2, 20(R)-Rh2, Rk2, and Rh3) by Enzymatic Conversion Combined with Acid Treatment and Evaluation of Its Anti-Cancer Activity

Song

Journal of Microbiology and Biotechnology

Choi

et al. 2017

The ginsenoside Rh2 has strong anti-cancer, anti-inflammatory, and anti-diabetic effects. However, the application of ginsenoside Rh2 is restricted because of the small amounts found in Korean white and red ginsengs. To enhance the production of ginsenoside Rh2-MIX (comprising 20()-Rh2, 20()-Rh2, Rk2, and Rh3 as a 10-g unit) with high specificity, yield, and purity, a new combination of enzymatic conversion using the commercial enzyme Viscozyme L followed by acid treatment was developed. Viscozyme L treatment at pH 5.0 and 50°C was used initially to transform the major ginsenosides Rb1, Rb2, Rc, and Rd into ginsenoside F2, followed by acid-heat treatment using citric acid 2% (w/v) at pH 2.0 and 121°C for 15 min. Scale-up production in a 10-L jar fermenter, using 60 g of the protopanaxadiol-type ginsenoside mixture from ginseng roots, produced 24 g of ginsenoside Rh2-MIX. Using 2 g of Rh2-MIX, 131 mg of 20()-Rh2, 58 mg of 20()-Rh2, 47 mg of Rk2, and 26 mg of Rh3 were obtained at over 98% chromatographic purity. Then, the anti-cancer effect of the four purified ginsenosides was investigated on B16F10, MDA-MB-231, and HuH-7 cell lines. As a result, these four rare ginsenosides markedly inhibited the growth of the cancer cell lines. These results suggested that rare ginsenoside Rh2-MIX could be exploited to prepare an anti-cancer supplement in the functional food and pharmaceutical industries.

“…However, administration of 500 mg of ginseng (standardized to 5% ginsenosides) in healthy individuals for 4 wk increased CYP3A4 enzyme activity by approximately 34% [6] . In addition, ginsenoside metabolites have been reported to have the potential to inhibit P- glycoprotein (P-gp) [7] , [8] , [9] .…”

Section: Introductionmentioning

confidence: 99%

Effect of Red Ginseng on cytochrome P450 and P-glycoprotein activities in healthy volunteers

Journal of Ginseng Research

Jeon

et al. 2016

BackgroundWe evaluated the drug interaction profile of Red Ginseng (RG) with respect to the activities of major cytochrome P450 (CYP) enzymes and the drug transporter P-glycoprotein (P-gp) in healthy Korean volunteers.MethodsThis article describes an open-label, crossover study. CYP probe cocktail drugs, caffeine, losartan, dextromethorphan, omeprazole, midazolam, and fexofenadine were administered before and after RG supplementation for 2 wk. Plasma samples were collected, and tolerability was assessed. Pharmacokinetic parameters were calculated, and 90% confidence intervals (CIs) of the geometric mean ratios of the parameters were determined from logarithmically transformed data using analysis of variance after RG administration versus before RG administration.ResultsFourteen healthy male participants were evaluated, none of whom were genetically defined as poor CYP2C9, 2C19, and CYP2D6 metabolizers based on genotyping. Before and after RG administration, the geometric least-square mean metabolic ratio (90% CI) was 0.870 (0.805–0.940) for caffeine to paraxanthine (CYP1A2), 0.871 (0.800–0.947) for losartan (CYP2C9) to EXP3174, 1.027 (0.938–1.123) for omeprazole (CYP2C19) to 5-hydroxyomeprazole, 1.373 (0.864–2.180) for dextromethorphan to dextrorphan (CYP2D6), and 0.824 (0.658–1.032) for midazolam (CYP3A4) to 1-hydroxymidazolam. The geometric mean ratio of the area under the curve of the last sampling time (AUClast) for fexofenadine (P-gp) was 0.963 (0.845–1.098). Administration of concentrated RG for 2 wk weakly inhibited CYP2C9 and CYP3A4 and weakly induced CYP2D6. However, no clinically significant drug interactions were observed between RG and CYP and P-gp probe substrates.ConclusionRG has no relevant potential to cause CYP enzyme- or P-gp-related interactions.Clinical trial registration number (ClinicalTrials.gov): NCT02056743.