Pharmacokinetic comparison of ginsenoside metabolite IH-901 from fermented and non-fermented ginseng in healthy Korean volunteers.

ETHNOPHARMACOLOGICAL RELEVANCE: IH-901 (20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol) is a novel ginseng saponin metabolite formed by human intestinal bacteria and is known to have antitumor and antimetastatic effects. However, there has been no pharmacokinetic study of IH-901 in human beings. AIM OF THE STUDY: The aim of this study was to investigate the pharmacokinetic differences of IH-901 from fermented and non-fermented ginseng. MATERIALS AND METHODS: To investigate whether the pharmacokinetics of IH-901 differ between fermented and non-fermented ginseng, an open label, randomized, single dose, fasting, two-period, cross-over, pharmacokinetic study was conducted. A total of 24 healthy Korean male volunteers participated in this study. All subjects were allocated into two equal groups and administered 3g of fermented or non-fermented Panax ginseng. Serial blood samples for pharmacokinetic analysis were collected in the 24 h after dosing. Plasma IH-901 concentration was measured by a validated high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Pharmacokinetic parameters including AUC(t), C(max), and T(max) were calculated by noncompartmental models in the BA-CALC program (KFDA, 2008, 1.0.0, Korea). RESULTS: After oral administration of fermented ginseng, 5 subjects experienced diarrhea. The means of AUC(t) and C(max) were significantly different between the two groups. In the fermented ginseng group, AUC(t) was 2083.09±91.97 ng h/mL, a 15.5-fold increase over that of IH-901 from the non-fermented group (134.50±63.10 ng h/mL), and the mean C(max) was 325.00±91.97 ng/mL in the fermented ginseng group, a 27-fold higher value than that in the non-fermented group (13.88±7.24 ng/mL). T(max) was 3.29±1.00 and 12.04±4.96 h in the fermented and non-fermented group, respectively. CONCLUSIONS: The results of this study showed that the pharmacokinetic parameters of IH-901 from fermented Panax ginseng are different from those of non-fermented ginseng, from which IH-901 is formed by intestinal fermentation.

Suppressive effect by Hizikia fusiforme on the production of tumor necrosis factor in BV2 murine microglial cells.

BACKGROUND: Hizikia fusiforme has been commonly used as food in Korea. Antioxidant effect of Hizikia fusiforme, however, was recently reported. Thus, herein, we investigated the effect of Hizikia fusiforme on the production and expression of tumor necrosis factor (TNF), a major proinflammatory mediator, in lipopolysaccharide (LPS)-activated BV2 microglial cells. METHODS: Cells were pre-treated with 5 or 50 mug/ml Hizikia fusiforme and treated with 1 mug/ml LPS. The production of TNF was measured by enzyme-linked immunosorbent assay (ELISA). The effect of Hizikia fusiforme on the expression of TNF was also performed by immunoblot analysis and reverse transcription-polymerase chain reaction (RT-PCR). Activation of nuclear factor kappab (NFkappab) was determined by electrophoretic mobility shift assay (EMSA). RESULTS: We observed that Hizikia fusiforme decreased the production of TNF. The inhibitory effect of the Hizikia fusiforme on the expression of TNF was confirmed by immunoblot and RT-PCR analyses. In addition, EMSA experiment revealed that Hizikia fusiforme blocked the LPS-induced activation of NFkappab. CONCLUSION: The present study suggests that Hizikia fusiforme may suppress LPS-stimulated TNF production via inhibition of NFkappab in murine microglial cells.