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At least 505 records · Page 28Linked to original sources
PubMed1999

Protopanaxatriol ginsenosides inhibit glucose uptake in primary cultured rabbit renal proximal tubular cells by arachidonic acid release.

Ginsenosides are involved in protective action against renal dysfunction and the regulation of renal functions. However, the effects of ginsenosides on glucose reabsorption are not yet known in renal proximal tubular cells. The aim of this study was to examine the effects of ginsenosides, protopanaxadiol (PD) saponin and protopanaxatriol (PT) saponin, on alpha-methyl-D-glucopyranoside (alpha-MG) uptake and its mechanism of action in primary cultured rabbit renal proximal tubular cells (PTCs). The alpha-MG uptake was inhibited by 90% by 0.5mM phloridizin and by removal of Na+ in the PTCs. These are typical characteristics described for the proximal tubule. To determine the time- and dose-dependent effects of PD and PT saponins on alpha-MG uptake, PTCs were incubated with different concentrations of PD and PT saponins (10-100 microg/ml) and for different time periods (from 10 min to 24 h). PT saponin (>/=50 microg/ml) from 30 min inhibited alpha-MG uptake; however, PD saponin did not alter the alpha-MG uptake at any doses and time periods. In the kinetic analysis of alpha-MG uptake, PT saponin produced a significant decrease in Vmax. The PT saponin induced inhibition of alpha-MG uptake was blocked by mepacrine, a phospholipase A2 inhibitor. In addition, PT saponin increased [3H] arachidonic acid release by 218% of that of control, and this effect was also completely blocked by mepacrine. In conclusion, PT saponin inhibited, in part, alpha-MG uptake through the phospholipase A2 signal pathway in primary cultured rabbit renal PTCs.

Animals↗
PubMed2002

Ginsenosides protect apical transporters of cultured proximal tubule cells from dysfunctions induced by h(2)o(2).

Oxidative stress has been implicated as a primary cause of renal failure in certain renal diseases. Indeed, renal proximal tubule is a very sensitive site to oxidative stress and retains functionally fully characterized transporters. It has been reported that ginsenosides have a beneficial effect on diverse diseases including oxidative stress. However, the protective effect of ginsenosides on oxidative stress has not been elucidated in renal proximal tubule cells. Thus, we examined the effect of ginsenosides on oxidative stress-induced alteration of apical transporters and its related mechanism in renal proximal tubule cells. In the present study, hydrogen peroxide (H(2)O(2)) (>10(-5) M) inhibited alpha-methyl-D-glucopyranoside uptake in a dose-dependent manner (p < 0.05). It also inhibited Pi and Na(+) uptake. At a concentration of 20 microg/ml, total ginsenosides significantly reduced H(2)O(2)-induced inhibition of apical transporters. In contrast, protopanaxadiol (PD) and protopanaxatriol (PT) saponins exhibited a less preventive effect than total ginsenosides (p < 0.05). Furthermore, we examined its action mechanism. H(2)O(2) increased lipid peroxide formation, arachidonic acid (AA) release, and Ca(2+) uptake. These effects on H(2)O(2) were significantly prevented by total ginsenosides and PD or PT sanponins. However, total ginsenosides appear to be more protective than PD and PT saponins (p < 0.05). In conclusion, ginsenosides prevented H(2)O(2)-induced inhibition of apical transporters via a decrease in oxidative stress, AA release, and Ca(2+) uptake in primary cultured renal proximal tubule cells.

Animals↗
PubMed1998

Saikosaponin b2 induces differentiation without growth inhibition in cultured B16 melanoma cells.

Treatment with 5 microM of saikosaponin (SS) b2 for 30 days was found to induce differentiation of B16 melanoma cells, with potentiation of expressions of melanogenesis and tyrosinase. To explore the mechanism of this effect, we observed the cell growth, cell cycle and morphology, and found that SSb2 did not affect any of these parameters. That is, SSb2 induced the differentiation of B16 melanoma cells without growth inhibition or cytotoxicity under conditions of low dose and long-term treatment. Phorbol ester, a protein kinase C (PKC) activator, markedly inhibited the expressions of melanogenesis and tyrosinase in both the control B16 melanoma cells and the long-term treated B16 melanoma cells. Down-regulation of the PKC activity may be involved in the effects of SSb2.

Animals↗
PubMed1997

Enzymes responsible for the metabolism of saikosaponins from Eubacterium sp. A-44, a human intestinal anaerobe.

From a human intestinal bacterium, Eubacterium sp. A-44, which is capable of hydrolyzing saikosaponins to saikogenins, two glycosidases, beta-D-glucosidase and a novel type of beta-D-fucosidase, were isolated and characterized as saikosaponin-hydrolyzing beta-D-glucosidase and prosaikogenin-hydrolyzing beta-D-fucosidase. Relative to the hydrolyzing activities toward saikosaponins a, b1 and b2, the beta-D-glucosidase showed lower ability to hydrolyze saikosaponin d, but no ability to hydrolyze saikosaponin c or prosaikogenins. By Sephacryl S-300 column chromatography, the molecular weight of prosaikogenin-hydrolyzing beta-D-fucosidase was estimated to be about 130 kDa. The beta-D-fucosidase could hydrolyze prosaikogenins A and F, but not prosaikogenins D and G or saikosaponins. Relative to p-nitrophenyl beta-D-fucoside-hydrolyzing activity, this enzyme had 32.0% and 22.2% of its hydrolyzing ability toward p-nitrophenyl beta-D-glucoside and p-nitrophenyl beta-D-galactoside, respectively. p-Nitrophenyl beta-D-fucoside-hydrolyzing activity was inhibited by D-fucose, and was weakly inhibited by D-glucose, D-glucono delta-lactone, D-galactose and D-galactono delta-lactone. By combining these two glycosidases, saikosaponins a and b1 were converted to their saikogenins via the corresponding prosaikogenins.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1998

Metabolism and pharmacokinetics of orally administered saikosaponin b1 in conventional, germ-free and Eubacterium sp. A-44-infected gnotobiote rats.

The metabolic fate of saikosaponin b1 (1) was investigated using conventional, germ-free and Eubacterium sp. A-44-infected gnotobiote rats. After the oral administration of 1 to germ-free rats at a dose of 50 mg/kg, no metabolite was detected in the plasma, the cecal contents or the cumulative feces through the experiment. On the other hand, when 1 was orally given to the Eubacterium sp. A-44-infected gnotobiote rats, considerable amounts of its metabolites, prosaikogenin A (2) and saikogenin A (3), were detected in the rat plasma with the respective AUC0-10 h values of 17,424 and 22,260 pmol.min/ml, similar to the case of its oral administration to conventional rats (AUC0-10 h values of 9,936 and 12,414 pmol.min/ml for 2 and 3, respectively). Furthermore, significant amounts of both metabolites were detected in the cecal contents and the cumulative feces of the gnotobiote and conventional rats, but not in those of the germ-free rats, within 10 h after the administration. Fecal and cecal activities of hydrolyzing 1 and 2 were found in the gnotobiote and conventional rats, though there were no detectable activities in the germ-free rats. Accordingly, both hydrolyzing activities in the intestinal bacteria, such as Eubacterium sp. A-44, are essential for the appearance of 2 and 3 in the rat plasma and cumulative feces, since orally administered 1 was poorly absorbed from the gastrointestinal tract.

Animals↗
PubMed1999

Antagonism of saikosaponin-induced prostaglandin E2 release by baicalein in C6 rat glioma cells.

There are several Kampo medicines (Chinese herbal medicines) containing both Bupleuri Radix and Scutellariae Radix, which are used for the treatment of inflammation. Saikosaponins are derived from Bupleuri Radix, and baicalein is from Scutellariae Radix. The present study was undertaken to investigate the pharmacological interaction of saikosaponin b1 and baicalein in prostaglandin E2 (PGE2) release from C6 rat glioma cells in vitro. Saikosaponin a, b1 and d potently stimulated PGE2 release, while saikosaponin b2 and c moderately stimulated PGE2 release. Saikosaponin b1 caused an irreversible elevation of intracellular Ca2+ concentration, which was eliminated by removing extracellular Ca2+. On the other hand, baicalein inhibited saikosaponin b1-induced PGE2 release in a concentration-dependent manner. These results suggest that saikosaponins are activators of PGE2 release, and baicalein is one of the functional inhibitors of PGE2 release by saikosaponins.

Animals↗
PubMed2002

Prevention of growth and metastasis of murine melanoma through enhanced natural-killer cytotoxicity by fatty acid-conjugate of protopanaxatriol.

Ginsenosides, the glycosides of Panax ginseng, are metabolized (deglycosylated) by intestinal bacteria after oral administration. 20(S)-Protopanaxatriol (M4) is the main bacterial metabolite of protopanaxatriol-type ginsenosides and mediates their antitumor effects. To clarify the mechanism of the M4-mediated antitumor effect, the antitumor activity and metabolism of M4 was examined, using the C57BL/6 mice implanted with B16-BL6 melanoma. The chronic oral administration of M4 inhibited the growth of B16-BL6 melanoma at the implanted site. Analyses using TLC, HPLC, MS and NMR suggest that orally administered M4 was absorbed from the small intestine into the mesenteric lymphatics followed by the rapid esterification of M4 with fatty acids and its accumulation in the tissues including the liver and lung. The administration of M4 prior to the intravenous injection of B16-BL6 cells abrogated the enhanced lung metastasis in the mice pretreated with 2-chloroadenosine more effectively than in those pretreated with anti-asialo GM1. The esterified M4 (EM4) did not directly affect tumor growth in vitro, whereas it stimulated splenic NK cells to become cytotoxic to tumor cells. These results indicate that the antitumor activity of M4 is based on the NK cell-mediated tumor lysis enhanced by EM4.

Administration, Oral↗
PubMed2004

The inhibitory effect of intestinal bacterial metabolite of ginsenosides on CYP3A activity.

The intestinal bacterial metabolites of ginsenosides are responsible for the main pharmacological activities of ginseng. The purpose of this study was to find whether these metabolites influence hepatic metabolic enzymes and to predict the potential for ginseng-prescription drug interactions. Utilizing the probe reaction of CYP3A activity, testosterone 6beta-hydroxylation, the effects of derivatives of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol families on CYP3A activity in rat liver microsomes were assayed. Our results showed that ginsenosides from the 20(S)-protopanaxadiol and 20(S)-protopanaxatriol family including Rb1, Rb2, Rc, Compound-K, Re, and Rg1 had no inhibitory effect, whereas Rg2, 20(S)-panaxatriol and 20(S)-protopanaxatriol exhibited competitive inhibitory activity against CYP3A activity in these microsomes with the inhibition constants (Ki) of 86.4+/-0.8 microM, 1.7+/-0.1 microM, and 3.2+/-0.2 microM, respectively. This finding demonstrates that differences in their chemical structure might influence the effects of ginsenosides on CYP3A activity and that ginseng-derived products might have potential for significant ginseng-drug interactions.

Animals↗
PubMed2005

Uptake and metabolism of ginsenoside Rh2 and its aglycon protopanaxadiol by Caco-2 cells.

The uptake and metabolism profiles of ginsenoside Rh2 and its aglycon protopanaxadiol (ppd) were studied in the human epithelial Caco-2 cell line. High-performance liquid chromatography-mass spectrometry was applied to determine Rh2 and its aglycon ppd concentration in the cells at different pH, temperature, concentration levels and in the presence or absence of inhibitors. Rh2 uptake was time and concentration dependent, and its uptake rates were reduced by metabolic inhibitors and influenced by low temperature, thus indicating that the absorption process was energy-dependent. Drug uptake was maximal when the extracellular pH was 7.0 for Rh2 and 8.0 for ppd. Rh2 kinetic analysis showed that a non-saturable component (Kd 0.17 nmol x h(-1) x mg(-1) protein) and an active transport system with a Km of 3.95 micromol x l(-1) and a Vmax of 4.78 nmol x h(-1) x mg(-1)protein were responsible for the drug uptake. Kinetic analysis of ppd showed a non-saturable component (Kd 0.78 nmol x h(-1) x mg(-1) protein). It was suggested that active extrusion of P-glycoprotein and drug degradation in the intestine may influence Rh2 bioavailability.

Caco-2 Cells↗
PubMed1983

Studies on the mechanism of anti-inflammatory activities of papyriogenin a and papyriogenin C.

The mechanism of anti-inflammatory action of papyriogenin A and C, obtained from Tetrapanax papyriferum, were investigated by the following methods; the cotton pellet granuloma test in normal and adrenalectomized rats, the blockade by anti-glucocorticoids of vascular permeability caused by serotonin in mice and the competition on 5 beta-reduction of steroidal compounds. The anti-inflammatory activity was observed in the decreasing order; papyriogenin C greater than papyriogenin A on the carrageenin-induced paw edema in mice, as reported in our previous paper. In a serotonin-induced paw edema, pretreatment with progesterone (50, 100 and 200 mg/kg) blocked completely the anti-inflammatory effects of papyriogenin A or C at 10 and 50 mg/kg. When actinomycin D (1 and 2 mg/kg) or cycloheximide (6 mg/kg) was given twice, simultaneously with papyriogenin A or C, during the latent period for the manifestation of the anti-inflammatory effect, the anti-inflammatory effects of papyriogenin A and C were blocked completely by s.c. administration. The effects of papyriogenin A or C, 30 mg/kg p.o., on the cotton pellet granuloma test in adrenalectomized rats were similar to those of normal rats. On the other hand, the competitive effects of papyriogenin A and C on 5 beta-reduction of testosterone and cortisol were recognized to be significant. These activities of papyriogenin A and C are explained by their steroidal actions in the target cell and their competitive effects in endogenous corticoid metabolism in liver.

Animals↗
PubMed1985

Structural transformation of saikosaponins by gastric juice and intestinal flora.

Structural transformation of saikosaponin a and saikosaponin d, main components of Bupleuri Radix, were investigated using rat gastric juice (pH 1.5) and mouse intestinal flora in vitro and the excretion of saikosaponin derivatives in rat feces was also studied. Quantitative analysis of saikosaponins and their derivatives was carried out by high performance liquid chromatography. By the incubation of saikosaponins in rat gastric juice, saikosaponin a decreased with time dependently. After 3 h, saikosaponin a disappeared completely and saikosaponin b1 which possessed heteroannular diene moiety at C-11,13(18) and saikosaponin g which possessed homoannular diene moiety at C-9(11),12 were detected with the ratio of 3:1. On the other hand, saikosaponin d rapidly changed to only saikosaponin b2 (heteroannular diene structure) completely 30 min after the incubation. Next, by the anaerobic incubation of saikosaponin a with mouse intestinal flora, the formation of saikogenin F, a genuine aglycone of saikosaponin a, reached to the maximum 1 h after the incubation and its yield was 80%. A minor peak of prosaikogenen F, a monofucoside of saikogenin F, was also detected at 15 min. By the same procedures, saikosaponin b1, g, d and b2 also changed to the corresponded prosaikogenin A, H, G and D and saikogenin A, H, G and D with the almost similar pattern to that of saikosaponin a. Finally, the contents of nine excreted metabolites from saikosaponin a, 5 and 20 mg/kg, in feces after its oral administration was investigated using fasted or non-fasted rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Studies of the combined use of steroid and Shosaikoto, one of the Kampohozai (Chinese traditional medicine), on pituitary adrenocortical axis function and immune responses.

The combined effects of Shosaikoto, one of the Kampohozai (Chinese traditional medicine), and prednisolone were examined for suppressive actions on pituitary adrenocortical axis function and immune response induced by prednisolone using rats and mice. The administration of Shosaikoto, 1.2 g/kg p.o., for 45 d showed a tendency to increase adrenal weight. By the combined use of Shosaikoto, 0.12 and 1.2 g/kg p.o., and prednisolone, 0.016 g/kg p.o., for 45 d, the decrease of adrenal weight induced by the treatment with prednisolone was restored. The administration of Shosaikoto, 1.2 g/kg p.o., elevated the blood corticosterone level. In the case of combined use, Shosaikoto, 0.12 and 1.2 g/kg p.o., inhibited the decrease of blood corticosterone level induced by the treatment with prednisolone, 0.004 g/kg p.o., and Shosaikoto, 1.2 g/kg p.o., inhibited the decrease of blood corticosterone level induced by the treatment with prednisolone, 0.016 g/kg p.o. On the other hand, the administration of Shosaikoto, 1.2 g/kg p.o., for 7 d reduced the number of hemolytic plaque forming cells (HPFC) in spleen cells. But, Shosaikoto, 1.2 g/kg p.o., administered for 7 d inhibited the decrease of the number of HPFC induced by the treatment with prednisolone, 0.01 and 0.03 g/kg s.c., for 3 d. Furthermore, Shosaikoto, 1.2 g/kg p.o., restored the number of rosette forming cell (RFC) which decreased by prednisolone, 0.03 g/kg s.c. The decrease of 7S HA titer of the serum by the treatment with prednisolone, 0.01 g/kg s.c., was also inhibited by the combination with Shosaikoto, 1.2 g/kg p.o.

Adrenal Glands↗