• Archives of Pharmacal Research
• /
• v.27 no.4
• /
• pp.402-406
• /
• 2004

This research team found in previous studies, that the ginseng saponin metabolite IH901 induces apoptosis in HepG2 cells via a mitochondrial-mediated pathway, which resulted in the activation of caspase-9 and subsequently of caspase-3 and -8. Based on these results, the involvement of the Fas/Fas ligand (FasL) death-receptor pathway, in IH901-induced apoptosis in HepG2 cells, was investigated. Levels of Fas and the Fas ligand (FasL) mRNA or protein were not increased by IH901, rather they were decreased significantly at 18 h post treatment. Soluble FasL (sFasL) was detectable by immunoprecipitation analysis En the medium of HepG2 cells treated with IH901. Increased levels of sFasL were inversely correlated with the levels of FasL. Preincubation of HepG2 cells with antagonistic anti-Fas antibody showed little protective effect, if any, on IH901-induced cell death. At a $30{\mu}M$ (24 and 48 h) and $40{\mu}M$ (24 h) concentration of IH901, the cytotoxic effect of IH901 was less then $50\%$, anti-Fas antibody prevented IH901-induced cell death. However, at a $60{\mu}M$ (24 and 48 h) and $40{\mu}M$ (48 h) concentration of IH901, cell death rates were about $80\%$ or more and most of the chemopreventive and chemotherapeutic effects of IH901 were manifested. Blocking the Fas receptor did not influence IH901-induced cell death. These results indicate that the Fas/FasL system is engaged, but not required for IH901-induced cell death, at pharmacologically significant concentrations.

• YAKHAK HOEJI
• /
• v.50 no.6
• /
• pp.345-350
• /
• 2006

The pharmacological properties of ginseng are mainly attributed to ginsenosides, the active constituents that are found in the extracts of different species of ginseng. Lately; the studies on ginsenosides are mainly focused on IH-901, a major intestinal bacterial metabolite of ginsenosides. In this study; we examined the anti-diabetic activity of IH-901 in C57BU61 db/db mice model. IH-901 was administrated orally at a dose of 20 mg/kg for 5 weeks. During the experimental period, body weight and blood glucose levels were measured every week. After 5 weeks, db/db mice were sacrificed and diabetic parameters were analyzed. IH-901 treated group showed a significant decrease in fasting blood glucose levels (from 10.5 mM to 9.4 mM), insulin resistance index (from 163.6 to 100.2) and triglyceride levels (from 115.3 to 70.1) compared to the diabetic control. In Pancreatic islets morphology; IH-901 treated group revealed much less infltrated mononuclear cells, indicating that IH-901 recovered ${\beta}$-cell damage due to hyperglycemia. In addition, IH-901 upregulated expressions of glucose transporter 4 (GLUT4) and PPAR-${\gamma}$ in skeletal muscle and adipose tissue, respectively. Taken together IH-901might be a potential anti-hyperglycemic agent with insulin sensitizing effect.

• Biomolecules & Therapeutics
• /
• v.11 no.3
• /
• pp.183-189
• /
• 2003

General phannacological properties of IH-901, a new pharmacological composition as an intestinal metabolite formed from ginseng protopanaxadiol saponins, were investigated in experimental animals administered orally and in vitro test system. IH-901 had no effects on general behavior, pentobarbital sleeping time, spontaneous motor activity, motor coordination of mice, normal body temperature, chemoshock produced by pentylenetetrazole and writhing syndromes induced by 0.8％ acetic acid at the dose of 25 and 250 mg/kg. Gastric secretion of rats and intestinal motility in mice were not also influenced by the administration of IH-901 at doses of 25 and 250 mg/kg. IH-901 (25 and 250 mg/kg) did not change the mean arterial blood pressure and heart rate in conscious rats. IH-901 had no effect on the respiratory rate at the same doses when it was given to anesthetized rats. In in vitro experiments, IH-90l at the concentration of 25$\mu\textrm{g}$/L did not show any direct effect and inhibitory or augmentative action on the histamine-or acetylcholine-induced contractions in the isolated ileum of guinea-pig. Based on these results, it was concluded that IH-901 did not induce any adverse effects in experimental animals.

• Journal of Pharmaceutical Investigation
• /
• v.34 no.5
• /
• pp.385-391
• /
• 2004

The purpose of the present study was to formulate the aqueous solution of $20-O-{\beta}-D-glucopyranosyl-20(S)-protopanaxadiol\;(IH-901)$, an intestinal bacterial metabolic derivative from Ginseng protopanaxadiol saponin. For this purpose, the effects of various solubilization agents such as cosolvents [ethanol, propylene glycol (PG), polyethylene glycol 300 (PEG 300), polyethylene glycol 400 (PEG 400), glycerin], surfactants $(Tween\;80,\;Cremophor^{\circledR}\;RH40,\;Cremophor^{\circledR}\;EL,\;Poloxamer\;407,\;Poloxamer\;188)$ and a complexation agent $[hydroxypropyl-{\beta}-cyclodextrin\;(HPBCD)]$, on the solubility of IH-90l in aqueous solution were evaluated. The solubility of IH-901 in water was under $1\;{\mu}g/ml\;at\;20^{\circ}C$. Cosolvents such as ethanol, PG, PEG 300, PEG 400 and glycerin did not enhance the solubility of IH-901 at the 0 - 40% concentration range. The solubility of IH-901 was significantly elevated by the addition of cosolvents over the 80% concentration range. On the other hand, tween 80, $Cremophor^{\circledR}\;EL,\;Cremophor^{\circledR}\;RH40$ and HPBCD showed enhanced effects on the solubility of IH-901. The enhanced effects of Poloxamer 407 or Poloxamer 188 on the IH-901 solubility were less pronounced compared with $Cremophor^{\circledR}\;EL\;or\;Cremophor^{\circledR}\;RH40$. As a results, $Cremophor^{\circledR}$ aqueous solution was selected as an optimum solvent system. The aqueous solutions containing 10% $Cremophor^{\circledR}\;EL$ and 7% $Cremophor^{\circledR}\;RH40$ were formulated as dosing solutions containing 5.0 mg/ml of IH-901 for its intravenous and oral administration, respectively. The formular showed physical stability after stored for 7 days at $4^{\circ}C$.

• Archives of Pharmacal Research
• /
• v.20 no.6
• /
• pp.539-544
• /
• 1997

Anti-metastatic activities of IH901, an intestinal bacterial metabolic derivative formed from Ginseng protopanaxadiol saponins, was determined in vitro and in vivo. Under in vitro conditions, IH901 inhibited the migration of bovine aortic endothelial cells 25 times stronger than suramin and suppressed the invasion of HT1080 human fibrosarcoma cells into reconstituted basement membrane components of Matrigel 1000 times stronger than RGDS peptide. IH901 also showed inhibitory effect on type-IV collagenase secretion from HT 1080 cells and platelet aggregation. When the anti-metastatic activity of IH901 was evaluated in comparison with that of 5-FU using a spontaneous lung metastatic model of Lewis lung carcinoma, the administration of IH901 (10 mg/kg p. o.) to tumor-bearing mice led to a significant decrease in lung metastasis (43% of untreated control), which was slightly more effective than that obtained with 5-FU (56% of control). Thus, IH901 seems to exhibit its anti-metastatic activity partly through the inhibition of tumor invasion which results from the blockade of type IV collagenase secretion and also through anti-platelet and anti-angiogenic activities.

• YAKHAK HOEJI
• /
• v.47 no.1
• /
• pp.52-55
• /
• 2003

Antidiabetic activities of white ginseng 50％ ethanol extract (WGE) and IH901, an intestinal metabolite of ginsenoside R $b_1$, were compared in multiple low dose streptozotocin (STZ)-induced diabetic rats. WGE or IH901 were coadministered with STZ on Day 1 at dose of 100 and 300 mg or 10 and 30 mg, respectively, and continually administered for 16 days. STZ dissolved in citrate boner was injected intraperitoneally at dose of 20 mg/kg for 5 consecutive days. During the experiment, plasma glucose level and body weight were measured every 4$^{th}$ day. Amount of food and water intake were evaluated once a week and compared between groups. WGE and IH901 both significantly reduced the plasma glucose levels on Day 16 as compared with those of the diabetic control group. In the meantime, amount of food and water intake in WGE-and IH901-treated groups were significantly improved in a dose dependent fashion as compared with those of the diabetic control group. Taken together WGE and IH901 showed the comparable antidiabetic activities at the corresponding doses used in this experiment.

• Molecular & Cellular Toxicology
• /
• v.3 no.4
• /
• pp.254-261
• /
• 2007

20-O-($\beta$-D-Glucopyranosyl)-20 (S)-protopanaxadiol (IH-901) is one of the major metabolites of ginsenosides from Panax ginseng, and is suggested that IH-901 has been associated with various pharmacological and physiological activities. In this study, we demonstrate that IH-901 induced anti-inflammation in HT-29 human colon adenocarcinoma cells. Our results showed that IH-901 inhibited cell proliferation of HT-29 in a time- and dose-dependent manner. We also found that IH-901 was significantly decreased expression of iNOS compared with non-treated. We observed effect of IH-901 related with inflammatory genes using by cDNA microarray. We were known that the 34 inflammatory genes such as E2F, CDK6, TNF-$\alpha$, and PKC were down-regulated. Thus, these results suggest that IH-901 may have a potential preventive factor to improving cancer induced by chronic inflammation.

• Proceedings of the PSK Conference
• /
• 2002.10a
• /
• pp.422.2-423
• /
• 2002

The purpose of the present study was to investigate the hepatic uptake and biliary excretion of IH-901. a potential anticancer agents. in rats. IH-901 was mainly distributed into the liver after its iv administration at the dose of 10-30 mg/kg. The liver concentration of IH-901 at 7 min after its Iv administration was comparable with its initial concentration of the plasma. Moreover. recovery ratio of IH-901 in the bile for 6 hr was more than 40% after its iv administration. (omitted)

• Food Science and Biotechnology
• /
• v.14 no.4
• /
• pp.558-560
• /
• 2005

Hepatoprotective effects of white ginseng extract (WGE), and IH-901 (20-O-${\beta}$-D-glucopyranosyl-20(S)-protopanaxadiol) derived from intestinal metabolite of ginsenoside $Rb_1$ were studied using two experimental animal models with chemical-induced hepatic damage. Administration of WGE (200 and 500 mg/kg) and IH-901 (0.01, 0.05, and 0.1 mM/kg) significantly decreased aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels in acute hepatitic mice induced by $CCl_4$. Administration of WGE (l00 mg/kg) and IH-901 (0.02, 0.04, and 0.08 mM/kg) significantly decreased AST and ALT levels in acute hepatitic rats induced by D-galactosamine. AST and ALT levels of IH-901 groups decreased. These results suggested WGE and IH-901 may have protective effects against chemical-induced hepatic damage.

• Journal of Ginseng Research
• /
• v.27 no.3
• /
• pp.129-134
• /
• 2003

When ginsenoside $R_{*}$b1/ and $R_{b2}$ were anaerobically incubated with human fecal microflora, these ginsenosides were metabolized to compound K (IH-901). When ginsenoside $R_{g3}$ was anaerobically incubated with human fecal microflora, the ginsenoside $R_{g3}$ was metabolized it to ginsenoside $R_{h2}$. Among ginsenosides, IH-901 and 20(S)-ginsenoside $R_{h2}$ exhibited the most potent cyotoxicity against tumor cells: 50% cytotoxic concentrations of IH-901 in the media with and without fetal bovine serum (FBS) were 27.1-31.6 $\mu$M and 0.1-0.61 $\mu$M, and those of 20(S)-ginsenoside $R_{h2}$ were 37.5->50 and 0.7-7.1 $\mu$M, respectively. The cytotoxic potency of ginsenosides was IH-901>20(S)-ginsenoside R $h_{h2}$》20(S)-ginsenoside $R_{g3}$>ginsenoside $R_{b1}$(equation omitted) $R_{b2}$.EX>$R_{b2}$./.