• Archives of Pharmacal Research
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• v.22 no.1
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• pp.30-34
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• 1999

When liriodendrin or syringin was incubated for 24 h with human intestinal bacteria, two metabolites, (+)-syringaresinol$\beta$--D-glucopyranoside and (+)-syringaresionl, from liriodendrin and one metabolite, synapyl alcohol, from syringin were produced. The metabolic time course of liriodendrin was as follows: at early time liriodendrin was converted to (+)-syringaresinol-$\beta$-D-glucopyranoside, and then (+)-syringaresinol. The in vitro cytotoxicities of these metabolites, (+)-syringaresinol and synapyl alcohol, were superior to those of liriodendrin and syringin.

• Natural Product Sciences
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• v.6 no.4
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• pp.165-169
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• 2000

In vitro cytotoxic activities of cisplatin combined with Chungpesagan-tang or puerarin, which were treated with or without human intestinal bacteria, were measured. When cisplatin was combined with Chungpesagan-tang and its ingredient treated without intestinal bacteria, they did not affect the in vitro cytotoxicity of cisplatin against tumor cell lines. However, when cisplatin was combined with intestinal bacteria-treated Chungpesagan-tang and its ingredients, the cytotoxicities against SNU C4, L1210, A549 and P388 tumor cell lines were synergistically increased. Puerarin, which was isolated from Puerariae Radix, did not show in vitro cytotoxicity. However, its metabolite, daidzein, showed potent cytotoxicity against tumor cell lines and was synergistic by the combined usage of cisplatin. These results suggest that natural glycosides are not only prodrugs which can be transformed to active compounds by intestinal microflora, but the combined usage of cisplatin with natural components, such as daidzein, and herbal medicinal polyprescriptions, such as Chungpesagan-tang, may be a new method for prevention and minimization of the toxicity of cisplatin.

• Biomolecules & Therapeutics
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• v.17 no.4
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• pp.430-437
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• 2009

Metabolites of Soyasaponin I, a major constituent of soybean, by human intestinal microflora were investigated by LC-MS/MS analysis. We found four peaks, one parental constituent and three metabolites: m/z 941 [M-H]$^-$, m/z 795 [M-rha-H]$^-$, m/z 441 [aglycone-$H_2O$+H]$^+$, and m/z 633 [M-rha-gal-H]$^-$, which was an unknown metabolite, soyasapogenol B 3-$\beta$-D-glucuronide. When soyasaponin I was incubated with the human fecal microbial fraction from ten individuals for 48 h, soyasaponin I was metabolized to soyasapogenol B via soyasaponin III and soyasapogenol B 3-$\beta$-D-glucuronide or via soyasaponin III alone. Both soyasaponin I and its metabolite soyasapgenol B exhibited estrogenic activity. Soyasaponin I increased the proliferation, mRNA expression of c-fos and pS2, in MCF7 cells more potently than soyasapogenol B. However, soyasapogenol B showed potent cytotoxicity against A549, MCF7, HeLa and HepG2 cells, while soyasaponin I did not. The cytotoxicity of soyasapogenol B may prevent its estrogenic effect from increasing dose-dependently. These findings suggest that orally administered soyasaponin I may be metabolized to soyasapogenol B by intestinal microflora and that soyasapogenol B may express a cytotoxic effect rather than an estrogenic effect.

• Journal of Ginseng Research
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• v.37 no.4
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• pp.451-456
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• 2013

Compound K is a major metabolite of ginsenoside Rb1, which has various pharmacological activities in vivo and in vitro. However, previous studies have focused on the pharmacokinetics of a single metabolite or the parent compound and have not described the pharmacokinetics of both compounds in humans. To investigate the pharmacokinetics of ginsenoside Rb1 and compound K, we performed an open-label, single-oral dose pharmacokinetic study using Korean Red Ginseng extract. We enrolled 10 healthy Korean male volunteers in this study. Serial blood samples were collected during 36 h after Korean Red Ginseng extract administration to determine plasma concentrations of ginsenoside Rb1 and compound K. The mean maximum plasma concentration of compound K was $8.35{\pm}3.19$ ng/mL, which was significantly higher than that of ginsenoside Rb1 ($3.94{\pm}1.97$ ng/mL). The half-life of compound K was 7 times shorter than that of ginsenoside Rb1. These results suggest that the pharmacokinetics, especially absorption, of compound K are not influenced by the pharmacokinetics of its parent compound, except the time to reach the maximum plasma concentration The delayed absorption of compound K support the evidence that the intestinal microflora play an important role in the transformation of ginsenoside Rb1 to compound K.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.107.1-107.1
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• 2003

20-O-(${\beta}$-D-Glucopyranosyl)-20(S)-protopanaxadiol (IH901), an intestinal bacterial metabolite of ginseng saponins formed from ginsenosides Rb1, Rb2 and Rc, is suggested to be a potential chemopreventive agent. Here we show that IH901 induces apoptosis in human hepatoblastoma HepG2 cells. IH901 led to an early activation of procaspase-3 (6 h posttreatment), and the activation of caspase-8 became evident only later (18 h posttreatment). Caspase activation was a necessary requirement for apoptosis because caspase inhibitors significantly inhibited cell death by IH901. (omitted)

• Journal of Microbiology
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• v.39 no.3
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• pp.154-161
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• 2001

In recent years, colon cancer has been reported to be one of the most important causes of cancer morbidity and mortality in Korea. Epidemiological and experimental studies suggest that lactic acid bacteria (LAB) used to ferment dairy products inhibits colon carcinogenesis. The present study was designed to determine whether the colon cancer inhibitory effect of LAB (Bifidobacterium longum Hy8001; Bif and Lactobacillus acidophilus HY2l04; Lac) of Korean origin, is associated with intestinal microflora composition and certain enzyme activity in rats treated with azoxymethane (AOM). At five weeks of age, SD rats were divided at random into four (AOM alone, Bif, Lac, and Bif+Lac) groups. Oral administration of lactic acid bacteria cultures were performed daily until the termination of the study. Two weeks later all animals were given a subcutaneous injection of AOM dissolved in normal saline at a dose of 15 mg/kg of body weight once weekly for 2 weeks. Every two weeks for 10 weeks, five of the rats in each group were randomly chosen for fecal specimen collection. The fecal specimens were used for assay of $\beta$-glucuronidase and nitroreductase, and analysis of intestinal microflora composition. The activity of $\beta$-glucuronidase which plays an important role in the production of the carcinogenic metabolite of azoxymethane was remarkably increased in the AOM alone group after AOM injection and maintained the high level during the experiment. However, LAB inhibited the AOM-induced increase in $\beta$-glucuronidase activity. Nitroreductase activity decreased by 30-40% in LAB treated groups in comparison with that of the AOM alone group. The results of the present study suggest that LAB inhibits colon carcinogenesis by modulating the metabolic activity of intestinal micro-flora and improving the composition of intestinal microflora.

• The Korean Journal of Food And Nutrition
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• v.11 no.5
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• pp.488-492
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• 1998

This study was performed to investigate the influcence of various dietary fiber sources in Korea for activities of bacterial enzymes (${\beta}$-glucosidase, ${\beta}$-glucuronidase) and amounts of putrefactive product (indole) in aged rats. ${\beta}$-Glucosidase activity in the intestinal content was significantly lower in the seamustard 15% group than in other groups whereas the activity of ${\beta}$-glucuronidase was higher in the mugwort 15% group than other experimental groups. The amount of indole and pH in the intestinal content of aged rats were significantly lower in mugwort groups than in other groups.

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.126.1-126.1
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• 2000

• Archives of Pharmacal Research
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• v.23 no.2
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• pp.172-173
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• 2000

The relationship between the metabolites of glycyrrhizin (18$\beta$-glycyrrhetinic acid-3-O--D-glu-curonopyranosyl-($1{\rightarrow}2$)-$\beta$-D-glucuronide, CL) and their biological activities was investigated. By human intestinal microflora, CL was metabolized to 18$\beta$-glycyrrhetinic acid (GA) as a main product and to 18$\beta$-glycyrrhetinic acid-3-O-$\beta$-D-glucuronide (GAMG) as a minor product. The former reaction was catalyzed by Eubacterium L-8 and the latter was by Streptococcus LJ-22. Among GL and its metabolites, GA and GAMG had more potent in vitro anti-platelet aggregation activity than GL. GA also showed the most potent cytotoxicity against tumor cell lines and the potent inhibitory activity on rotavirus infection as well as growth of Helicobacter pylori. GAMG, the minor metabolite of GL, was the sweetest.

• Journal of Ginseng Research
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• v.33 no.2
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• pp.93-98
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• 2009

To understand the anti-allergic mechanism of compound K, which is a metabolite of ginsenoside Rb1, a main constituent of the root of Panax ginseng C.A. Meyer (family Araliaceae), its inhibitory effect against IgE-antigen complex IAC)-induced passive cutaneous anaphylaxis (PCA) reaction in mice and mRNA and protein expressions of allergic cytokines in lAC-stimulated RBL-2H3 cells were investigated. Orally administered ginsenoside Rb1 more potently inhibited PCA reaction when administered at 5 h prior to the lAC treatment than when administered at I h before. However, compound K orally administered 1 h before lAC treatment showed a more potent anti-PCA reaction effect than when treated at 5 h before. Orally administered ginsenoside Rb1 more potently inhibited PCA reaction induced by lAC in mice than intraperitoneally treated one, apart from orally administered its metabolite, compound K, which was more potent than the orally administered one. The compound K, a metabolite of ginsenoside Rb1, inhibited mRNA and protein expressions of IL-4 and TNF-${\alpha}$ and the activation of their transcription factor NF-$\kappa$B and MAPK in lAC-stimulated RBL-2H3 cells. These findings suggest that orally administered ginsenoside Rb1 may be dependent on its metabolism by intestinal microflora in the intestine and the compound K may improve allergic diseases by the inhibition of IL-4 and TNF-${\alpha}$ expresseion.