Ginseng (the root of Panax ginseng C.A. MEYER, Araliaceae) is frequently taken orally, as a crude substance, as a traditional medicine in Asian countries. The major components of ginseng are ginsenosides, which contain an aglycone with a dammarane skeleton.1,2) These ginsenosides have been reported to exhibit various biological activities, including anti-inflammatory action and antitumor effects (inhibition of tumor-induced angiogenesis and the prevention of tumor invasion and metastasis). [3][4][5] The pharmacological actions of these ginsenosides have been explained by their biotransformation by human intestinal bacteria. [6][7][8] For example, protopanaxadiol ginsenosides are transformed to 20-O-b-D-glucopyranosyl-20(S)-protopanaxadiol (compound K) by human intestinal bacteria. The metabolite compound K induces an antimetastatic or anticarcinogenic effect by blocking tumor invasion or preventing chromosomal aberration and tumorigenesis.5) Ginsenosides Re and Rg1 are also transformed to ginsenoside Rh1 or 20(S)-protopanaxatriol, which have exhibited potent antiallergic and antiinflammatory effects. [9][10][11][12] However, the antiiflammatory effect of protopanaxadiol ginsenosides, such as ginsenoside Rb1, and compound K, has not been studied.Therefore, we isolated ginsenoside Rb1 from ginseng and its metabolite compound K and investigated the antiinflammatory effect of ginsenoside Rb1 and its metabolite compound K (Fig. 1), using RAW264.7 cell induced by lipopolysaccharide (LPS). The RAW 264.7 cells were purchased from the Korean Cell Line Bank (Seoul, Korea).
MATERIALS AND METHODS
Materials
Isolation of Ginsenoside Rb1 and Its Metabolite Compound K by Human Intestinal Microflora GinsenosideRb1 and compound K were isolated from fermented Ginseng according to the previously published method.2,13) Ginsenoside Rb1 (2 g) from a BuOH extract of white ginseng (Kyung Dong Market, Seoul, Korea), was isolated by silica gel column chromatography using CHCl 3 -MeOH-H 2 O (10 : 3 : 1, lower layer), according to the previously reported methods.Fresh human feces (5 g) were suspended in TS broth, centrifuged at 500ϫg for 10 min, and the resulting supernatant * To whom correspondence should be addressed. Hoegi, Dongdaemun-ku, Seoul 130-701, Korea: and b Korea Food Research Institute; San 46-1, Baekhyun, Bundang-Ku, Seoungnam-Shi 463-420, Korea. Received August 25, 2004; accepted December 2, 2004 In this study, the antiinflammatory activities of ginsenoside Rb1, which is a main constituent of the root of Panax ginseng (Araliaceae), and of its metabolite compound K, as produced by human intestinal bacteria, on lipopolysaccharide (LPS)-induced RAW264.7 cells were investigated. Compound K potently inhibited the production of NO and prostaglandin E2 in LPS-induced RAW 264.7 cells, with IC 50 values of 0.012 and 0.004 mM, respectively. Compound K also reduced the expression levels of the inducible NO synthase (iNOS) and COX-2 proteins and inhibited the activation of NF-kB, a nuclear transcription factor. Compound K inhibite...