Oral administration of fermented red ginseng suppressed ovalbumin-induced allergic responses in female BALB/c mice.
Keywords: Food allergy Gut permeability IgE Ovalbumin Red ginseng fermented
Anti-allergic efficacy of red ginseng (RG) and fermented red ginseng (FRG) was evaluated. RG or FRG were administered to ovalbumin (OVA)-sensitized mice for 8 weeks. Immunoglobulins (1gs), Thl /Th2 type cytokines, and [beta]-lactoglobulin (BLG) in serum, and intestinal barrier-related molecules in jejunum were measured using enzyme-linked immunosorbent assay or reverse transcription-polymerase chain reaction. Mice sensitized with OVA increased serum Ig[G.sub.1], IgE, OVA-Ig[G.sub.1], and OVA-IgE. Both RG and FRG decreased serum IgE, OVA-IgE, and pro-inflammatory cytokines. Serum BLG, a marker of gut permeability, was significantly higher in sensitized animals and was decreased in mice fed RG or FRG. In addition, intestinal barrier-related markers such as MMCP-1, IL-4, TNF-[alpha], COX-2, and iNOS mRNA expressions were decreased by RG or FRG. Our results suggest in vivo anti-allergic activities of RG or FRG, which are associated with the regulation of Thl/Th2 balance, intestinal inflammation and subsequent the suppression of IgE.
[c] 2012 Elsevier GmbH. All rights reserved.
Food allergy can develop into life-threatening hypersensitivity responses and is often induced by food proteins such as ovalbumin (OVA). It occurs through abnormally heightened immune responses, particularly along with an abnormal increase in IgE production, which is considered a major event in mediating food allergic reactions. IgE is bound to the surface of mast cells and basophils which express high-affinity IgE receptors. Crosslinking of surface-bound IgE on these cells lead to the release of inflammation mediators and a large variety of cytokines, including TNF-[alpha] and Th2-associated cytokines such as IL-4 and I1-5. These cytokines play important roles in the late-phase reaction which is characterized by tissue infiltration of inflammatory cells. Accordingly, the inhibition of these mediators may be used as one of the important intervention strategies in the management of allergies (Bischoff 2009).
Intestinal permeability is a tightly controlled system for the passage of molecules from the intestinal lumen to the blood stream. The intestinal barrier, major sites of entry for most allergens, consists of multiple defense systems. Abrogation of the barrier might increase mucosal permeability and promote allergic inflammation. Increased intestinal permeability has been described in patients with eczema, asthma, and children with milk allergy (Benard et al. 1996; Majamaa and lsolauri 1996). In light of these facts, it is conceivable that maintaining the barrier function of the intestinal epithelium may prevent allergy.
Ginseng (root of Panax ginseng C.A. Meyer, family Araliaceae) is widely used in Asian countries as a traditional medicine to regulate a wide range of physiological functions (Christensen 2009). Ginsenosides are the major pharmacologically active components of ginseng and appear to be responsible for most of the activities of ginseng. Approximately 80 ginsenosides have been identified and comprise a triterpenoid dammarane structure with a varying number of sugar moieties. The steaming of fresh ginseng (white ginseng) at high temperature produces red ginseng (RG) (Cho et al. 2006). It has been reported that RG has more powerful pharmacological activities than white ginseng (Nam 2005). The differences in the biological activities of red and white ginseng may result from chemical structure changes in ginsenosides during the steaming process. Ginsenosides Rg3, Rg5 and F4 appeared after steaming raw ginseng for 2 h at 120 [degrees]C accounting for 39%, 19% and 6% of all ginsenosides, while the amounts of ginsenosides Re, Rb2 and Rb1 decreased (Kim et al. 2000). Fermented red ginseng (FRG) has been treated with microorganism and enzymes, which may increase the ginseng's efficacy dependent on the number and activity of each individual's intestinal flora. Comparison study of Hyun et al. (2009) reported that RG and FRG had a much greater effect in suppressing allergic inflammation that did white ginseng. In addition, recent study showed that fermented red ginseng improved nasal congestion symptoms and Rhinitis Quality of Life (Jung et al. 2011). Ginsenoside Rg3 is typically considered as a ginsenoside unique to RG products. Human intestinal bacterial fermentation of RG transformed Rg3 to mostly Rh2 by removing one sugar from the dihydroxydammaran moiety (Bae et al. 2002). Ginsenoside Rh2 exhibits potent cytotoxic effect against tumor cells, anti-allergic effect against mast cells, and anti-inflammatory activity in macrophage (Park et al. 2004; Park et al. 2003). It has been reported that another bioactive component, Rhl possessing a dammaran-trihydroxy moiety with single sugar at 6-0H position (Table 2), decreased anaphylactic responses in mice and inhibited histamine release from rat peritoneal mast cells (Park et al. 2004). Although, red ginseng contains many biologically active compounds, the absorption of these compounds depend on the composition of an individual's intestinal bacteria. In that sense, FRG can be very helpful to modulate the allergic inflammation.
In the present study, we investigated the effect of dietary RG or FRG on allergen-induced immune responses and intestinal permeability in female BALB/c mice.
Materials and methods
OVA (fraction, V), [beta]-LG, stop solution, citrate buffer (pH 9.6), bovine serum albumin (BSA) were purchased from Sigma Chemical Co. (St. Louis, MO, USA); cholera toxin was from List Laboratories; mouse Thl/Th2 cytokine cytometric bead array (CBA) kit, anti-mouse IgE, Ig[G.sub.1], Ig[G.sub.2a], HRP-conjugated anti-mouse IgG, capture antibodies, 3, 3', 5, 5'-tetramethylbenzidine (TMB) and falcon tubes (12 mm x 75 mm) were from BD Biosciences Pharmingen (CA, USA); Maxysorp 96 well plates were from Nunc (Roskilde, Denmark).
Both fermented red ginseng (FRG) and non fermented red ginseng (RG) powders were provided by Bifido Inc. (Hongcheon, Korea). Quantitative analysis of ginsenoside was carried out by HPLC. An aliquot of 20 [micro]l sample was injected onto the HPLC column (ZORBAX Eclipse XDB-Cl 8, 4.6 mm x 250 mm, 5 mm particle size) and separated using a mobile acetonitrile gradient (30% for the initial run, followed by 40% for 10.5 min, 100% for 10 min, and 30% for 5 min at a flow rate of 1 ml/min). The eluate was monitored at 203 nm. Ginsenosides compositions are shown in Table 1. Fig. 1 provides HPLC diagram of FRG and RG. In addition, structural elucidations of major peaks were shown in Table 2.
Table 1 Ginsenosides in RG and FRG samples. Peak [t.sub.R] Cinsenosides FRC (mg/g) RG (mg/g) FRG/RG no. (a) (min) l 3.0667 Ginsenoside 0.000 9.371 - Re 2 3.4500 Ginsenoside 10.571 4.796 2.20 Rg1 3 7.5500 Ginsenoside 1.429 1.121 1.27 Rf 4 8.2333 Ginsenoside 2.286 2.255 1.01 Rb1 5 8.9500 Ginsenoside 3.714 2.229 1.67 Re 6 9.1833 Ginsenoside 0.857 0.668 1.28 Rg2 7 9.7500 Ginsenoside 6.857 4.251 1.61 Rb2 8 10.1167 Ginsenoside 1.429 0.967 1.48 Rb3 9 11.9833 Ginsenoside 25.714 0.686 37.48 Rh1 10 15.5500 Ginsenoside 20.000 7.143 2.80 Rd 11 16.8333 Ginsenoside 6.857 0.875 8.00 Rg3 12 19.1000 Ginsenoside 2.857 0.057 50.12 Rh2 Crude 100.0 100.0 saponin (a.) [t.sub.R]: retention time. Table 2 Chemical structure of ginsenosides detected in chromatogram. Peak no. Structure 1 Re [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] 2 Rg1 [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] 3 Rf [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] 4 Rb1 [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] 5 Rc [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] 6 Rg2 [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] 7 Rb2 [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] 8 Rb3 [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] 9 Rh1 [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] 10 Rd [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] 11 Rg3 [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII] 12 Rh2 [MATHEMATICAL EXPRESSION NOT REPRODUCIBLE IN ASCII]
Balb/c mice were purchased from the Animal Centre of Japan SLC (Hamamatsu, Japan). Eight-week-old female mice with body weight of 18-20g, were used in all experiments. Mice were sensitized at 7 weeks of age and each group consisted of eight to twelve mice. Mice were maintained on a 12:12h light:dark cycle and allowed free access to tap water. The temperature and humidity were controlled at 23 [+ or -] 1 [degrees]C and 55 [+ or -] 10%, respectively. All procedures related to animal care were performed in accordance to the ethical guidelines of Sookmyung Women's University Animal Care and Use Committee.
Intragastric antigen sensitization and treatment
Sensitization was performed by 20 [micro]g OVA gavage with 10 [micro]g cholera toxin in 0.2 ml saline for 5 times once a week using a stainless steel blunt feeding needle. Mice in the non-sensitized control group received saline. Experimental diet included 0.1% or 0.3% red ginseng or fermented red ginseng. Mice were fed the experimental diet for 8 weeks starting at 1 week before the initial sensitization.
To determine possible changes in gut permeability and serum level of Igs and cytokines, the uptake of a bystander protein was determined in time after the challenge. Non-sensitized and OVA-sensitized animals were orally challenged with 100 [micro]l saline or 100 [micro]l of an OVA solution. The animals received an additional intragastric dose of [beta]-lactoglobulin (BLG; 100 [micro]g per mice) 30 min after the oral OVA challenge. Blood samples were collected at 45 min after the BLG administration. Sera were collected after centrifugation at 200 x g for 20 min and stored at -80[degrees]C until analysis.
For RT-PCR analysis, jejunum of small intestine was cut longitudinally and washed with saline. Small intestinal mucosa were then obtained and stored at -80 [degrees]C until RNA extraction (Fig. 2).
Measurement of serum OVA-specific IgE, Ig[G.sub.1], total IgE, and Ig[G.sub.1]
Serum OVA-specific IgE and Ig[G.sub.1] were quantified as follows. Ninety-six well plates were coated with 50 [micro]g/ml of OVA in coating buffer (citrate buffer, pH 9.6) at 4 [degrees]C overnight. The plates were washed with PBS-Tween 20 (0.05%; v/v), and then blocked with PBS-BSA (1%; w/v) for 1 h at room temperature. After washing, 100[micro]1 of diluted serum in PBS-BSA (1%; w/v) was added and incubated for 2 h at room temperature. After washing, corresponding biotinylated rat anti-mouse IgE or Ig[G.sub.1] was added and HRP conjugated substrate were incubated for 1 h at room temperature. The reactions were developed with the 3, 3', 5, 5'-tetramethylbenzidine substrate for 30 min at room temperature. The color reactions were stopped with [H.sub.2]S[O.sub.4] and read at 450 nm.
Total serum IgE, Ig[G.sub.1], and IgG were determined using ELISAs. To detect these antibodies, plates were coated with 2 [micro]g/ml of rat monoclonal anti-mouse IgE, Ig[G.sub.1], and Ig[G.sub.2a]. Antibody concentrations were calculated by comparison with purified mouse Ig isotype standard through linear regression analysis of the absorbance.
Measurement of Th1 and Th2
Thi (IL-2, IFN-[gamma], TNF-[alpha]) and Th2 cytokines (IL-4 and IL-5) were quantified simultaneously using a mouse Thl/Th2 cytokine cytometric bead array kit and CBA software according to the instruction. Individual cytokine concentration ratios were measured by BD Canto II Flow cytometer and indicated by their fluorescent intensities.
Measurement of gut permeability
To determine possible changes in gut permeability, the uptake of a bystander protein, serum BLG level was determined by bovine beta-lactoglobulin ELISA quantitation kit (Bethyl, Montgomery, TX) according to the instruction. BLG concentrations were calculated by comparison with standard curve through analysis of the absorbance.
Reverse transcription PCR (RT-PCR)
Total jejunum RNA was extracted using TRizol reagent according to the manufacturer's instructions. Extracted RNA pellet was dissolved in diethylpyrocarbonate-treated water for reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR was carried out using the one step RT-PCR kit according to the manufacturer's instructions. PCR product was placed in to 2% (w/v) agarose gels for electrophoresis. Gels were stained with ethidium bromide. Versa Doc Image analyzer (Bio Rad, Mississauga, ON, Canada) was used for quantitative analysis. Primers used in this experiment are shown in Table 3.
Table 3 Lists of primer sequences. Primers Sequences IL-4 Forward: ACG GCA CAG AGC TAT TGA TG Reverse: ATG GTG GCT CAG TAC TAC GA TNF-[alpha] Forward: AGT CCG GGC AGG TCT ACT TT Reverse: GAG GCA ACC TGA CCA CTC TC iNOS Forward: CCT CCT CCA CCC TAC CAA GT Reverse: CAC CCA AAG TGC TTC AGT CA COX-2 Forward: AAG ACT TGC CAG GCT GAA CT Reverse: CTT CTG CAG TCC AGG TTC AA MMCP-1 Forward: CCA GGT CTG TGT GGG AAG TT Reverse: GCT CTG GCT TGG AGA ATC TG GAPDH Forward: GAA CGG GAA GCT TGT CAT CAA Reverse: CTA AGC AGT TGG TGG TGC AG
Data are expressed as means [+ or -] SD. Differences between groups were considered significant at p < 0.05. Data were analyzed by Dun-can's multiple-range test. All analyses were performed using the SAS statistical packages (SAS Institute, Cary, NC).
RG and FRG suppress OVA-induced Igs
Fig. 3 shows serum 1g concentrations collected from mice after OVA sensitization. The highest serum IgE and Ig[G.sub.1] responses were recorded in OVA-sensitized control mice. In contrast, mice fed diet supplemented with 0.3% RG, 0.1% FRG and 0.3% FRG showed reduced IgE responses. Total Ig[G.sub.1] was significantly lower in all diet groups supplemented with RG or FRG compared to that of the OVA-sensitized controls.
We next measured the allergen specific 1gs and found that the concentrations of the OVA-specific IgE and Ig[G.sub.1] were significantly reduced in 0.1% FRG fed group. FRG was more effective in reducing Igs responses than FRG at 0.1% supplementation level. However, total Ig[G.sub.2a] and OVA-specific Ig[G.sub.2a] concentrations were not changed by RG or FRG supplementation.
RG and FRG modulate Thl/Th2 cytokines in serum
To identify the mechanisms through which IgE elevation is suppressed by oral intake of RG or FRG, serum Th1 and Th2 type cytokines in OVA-sensitized mice were measured. As shown in Table 4, serum concentrations of I1-5, TNF-[alpha], and IL-4 were elevated by OVA sensitization and were significantly reduced in animals fed diet supplemented with 0.1% RG, 0.3% RG, 0.1% FRG, and 0.3% FRG. No significant difference was observed between RG and FRG supplemented groups. No difference in IL-2 and IFN-[gamma] concentration was found.
Table 4 Effect of oral ginseng on serum Thi and Th2 cytokine production. Group TNF-[alpha] IL-4 (pg/ml) IFN-y(pg/ml) IL-2 (pg/ml) (pg/ml) C 3.7 [+ or -] 3.4 [+ or -] 5.5 [+ or -] 7.5 [+ or -] 2.4 (b) 1.8 (b) 2.6 (a) 3.2 (a) OVA 8.7 [+ or -] 6.4 [+ or -] 4.4 [+ or -] 4.5 [+ or -] 2.5 (a) 2.9 (a) 1.9 (a) 2.3 (b) 0.1 RG 4.6 [+ or -] 4.3 [+ or -] 4.6 [+ or -] 4.8 [+ or -] 3.4 (b) 1.8 (b) 2.4 (a) 2.2 (b) 0.3 RG 3.9 [+ or -] 3.0 [+ or -] 3.6 [+ or -] 3.8 [+ or -] 2.9 (b) 1.8 (b) 1.8 (a) 2.5 (b) 0.1 3.6 [+ or -] 3.7 [+ or -] 5.9 [+ or -] 5.7 [+ or -] FRG 2.1 (b) 1.3 (b) 5.1 (a) 2.8 (ab) 0.3 4.5 [+ or -] 4.2 [+ or -] 4.6 [+ or -] 4.6 [+ or -] FRG. 2.5 (b) 1.1 (b) 3.9 (a) 0.8 (b) Group IL-5 (pg/ml) C 11.1 [+ or -] 3.8 (ab) OVA 15.4 [+ or -] 5.8 (a) 0.1 RG 11.2 [+ or -] 3.7 (b) 0.3 RG 10.1 [+ or -] 4.8 (b) 0.1 12.2 [+ or -] FRG 3.6 (b) 0.3 12.0 [+ or -] FRG. 4.1 (b) Value are means[+ or -]S.D. (n = 10). Means with letters (a, b, c) within a column are significantly different from each other at p <0.05 as determined by Duncan's multiple range test. C: non-sensitization +AIN76A diet; OVA: OVA sensitization + AIN76A diet: 0.1 RG: OVA sensitization + AIN76A diet supplemented with 0.1% RG; 0.3 RG: OVA sensitization + AIN76A diet supplemented with 0.3% RG; 0.1 FRG: OVA sensitization + AIN76A diet supplemented with 0.1% FRG; 0.3 FRG: OVA sensitization + AIN76A diet supplemented with 0.3% FRG.
RG and FRG reduce gut permeability
Gut permeability was measured to determine whether this mechanism was involved in sensitization. The oral OVA challenge increased gut permeability as evidenced by an increased uptake of a bystander protein (BLG) (Fig. 4). Serum BLG level in previously sensitized mice was significantly increased by six times compared to that of the non-sensitized control mice and was significantly reduced in 0.1% RG, 0.3% RG, 0.1% FRG, and 0.3% FRG fed group.
RG and FRG modulate gene expression of inflammatory molecules in intestinal mucosa
To evaluate the mechanisms responsible for the anti-allergic responses, we measured mRNA expressions of inflammation-related molecules by RT-PCR. As shown in Fig. 5, MMCP-1, a marker of mast cell activation was increased in OVA sensitized mice and was decreased by dietary supplementation of FRG.
Several studies have reported that I1-4 induces the transepithelial transport of IgE through CD23, IgE low affinity receptor. Study results showed that IL-4 mRNA expression was increased in OVA-sensitized mice and decreased in RG and FRG-fed mice. FRG at 0.1% level supplementation was more effective in decreasing IL-4 expression compared to 0.1% RG supplementation.
It is well established that TNF-[alpha] is involved in the increased intestinal epithelial permeability by modulating the tight junction. As shown in Fig. 6, TNF-[alpha] mRNA expression of the intestinal mucosa was increased in OVA sensitized mice and was decreased in RG or FRG supplemented group.
In addition, RNA expression of COX-2 and iNOS were increased in OVA sensitized mice, while RG or FRG supplementation significantly decreased the expression in a dose-dependent manner.
In the present study, we evaluated the anti-allergic efficacy of red ginseng (RG) or fermented red ginseng (FRG) in the OVA-sensitized BALB/c mice model which share pathological and biological features of IgE-mediated food allergy in humans. Results indicated that the production of total or OVA-specific IgE and [IgG.sub.1] by OVA challenge was significantly suppressed by oral administration of RG or FRG supplemented at 0.1% level. We also found that FRG supplementation was more effective than RG supplementation.
The initiation and maintenance of IgE antibody production depend on the development of a selective Th2 type immune response (Sampson 2005). Th2 cells produce cytokines such as IL-4 and IL-5 that are required for the development of IgE antibody responses. In contrast, products of Thi cells such as IFN--y, antagonize IgE production through the inhibition of 1L-4 activity (Kimber and Dearman 1997). Allergen challenge induced the increased secretion of IL-4, IL-5, and TNF-[alpha], whereas the secretion of IFN-'y and IL-2 were suppressed. We observed significant decreases in Th2 type cytokines while Thi type cytokines were increased by both RG and FRG intake indicating that the suppression of IgE may be mediated by the modulation of the cytokine profile.
To further elucidate the mechanism of actions of RG and FRG, the intestinal permeability changes and related inflammatory indices were measured. Since intestinal mucosa membrane is the first barrier through which an allergen enters the systemic circulation, the reinforcement of this barrier can be a possible strategy to prevent allergic responses. In food allergy patients, intestinal permeability is increased with the oral allergen (Perrier et al. 2010; Knippels and Penninks 2003). The increase in intestinal permeability may facilitate the absorption of allergen into the circulation which leads to the systemic reactions. Our results also showed that intestinal permeability was increased by six times in OVA-sensitized mice when compared with that of the non-sensitized group, and RG or FRG supplementation suppressed OVA induced increases in intestinal permeability. Therefore, it is likely that oral administration of RG or FRG induces oral tolerance by limiting the uptake of an orally administered antigen through the intestinal tract.
We observed a moderate recruitment of mucosal mast cells. Mast cells have been established as key effector cells in allergic inflammation and population can increase up to tenfold in the chronic intestinal inflammation (Bischoff 2009). Mucosal mast cell protease-1 (MMCP-1), a marker of mast cell activation, was elevated in the small intestine as well as in the serum after OVA sensitization (Vaali et al. 2006; Bischoff 2007). It has been demonstrated that MMCPs are directly responsible for the increase of epithelial paracellular permeability and for the redistributed expression of tight junctions (Moriez et al. 2007). Our results showed that OVA sensitization increased intestinal mucosa MMCP-1 expression and RG or FRG supplementation suppressed the MMCP-1 expression. A previous study (Choo et al. 2003) reported that compound K, which was identified as a main metabolite of ginsenoside (produced by human intestinal bacteria), and Rh1 (25 mg/kg body weight) showed the most potent inhibitory activity on 13-hexosaminidase release from RBL-2H3 cells and on the PCA reaction as a marker of mast activation. The anti-allergic activity of this compound has been suggested to originate from its cell membrane stabilizing activity.
Nieuwenhuizen et al. (2007) showed that MMCP-1 expression was suppressed in IL-4R-/- mice compared to the wild type mice, indicating that MMCP-1 expression is closely related to the IL-4 signal. More importantly, intestinal mucosa IL-4 can regulate the transepithelial transport of IgE. It has been reported that IL-4 stimulates CD23, a low affinity IgE receptor, expression and plays an important role in IgE transepithelial transport (Montagnac et al. 2005). We showed that IL-4 mRNA expression in the intestinal mucosa was increased in OVA-sensitized mice, while it was reduced in 0.3% RG, 0.1% FRG and 0.3% FRG group. The above results suggest that RG and FRG possibly inhibited the IgE-Ag transport from the lumen of gut to the mucosa through inhibition of CD23 expression, following a reduction of IL-4 expression in the intestinal mucosa. FRG was more effective to suppress the production of MMCP-1 and IgE, and the expression of mucosal IL-4 than RG. The FRG used in our study contained 38 and 50 times more Rh1 and Rh2 than in RG, respectively. Recent studies reported that both Rh1 and Rh2 can alleviate inflammatory symptoms by reducing IgE in allergic animal model and may be a possible therapeutic agent for allergic diseases.
Intestinal epithelium permeability is known to be mediated by a few cytokines (Yu and Perdue 2000). TNF-a increases the rate of transcytosis and alters the tight junction permeability (Ma et al. 2004). The presence of TNF-[alpha] at the intestinal level was implicated by the presence of fecal TNF-[alpha] in allergic children after oral ingestion of allergen. Consistent with these results, we also showed that OVA sensitization induced TNF-[alpha] mRNA expression in the intestinal mucosa and RG or FRG supplementation suppressed the expression of these pro-inflammatory cytokines.
It has been established that TNF-[alpha] stimulation increases inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Both iNOS and COX-2 have been reported to induce deleterious effects in the intestine (Xu et al. 2002). We demonstrated that the induction of iNOS and COX-2 mRNA expression in the intestinal mucosa by OVA sensitization, while RG or FRG supplementation suppressed the expression of these pro-inflammatory molecules in the intestinal mucosa. Park et al. (2004) showed that ginsenoside Rh1 inhibited iNOS and COX-2 protein expression in RAW 264.7 cells, and the activation of the transcription factor, NF-kappa B, in the nuclear fractions.
In conclusion, the present results demonstrate that RG or FRG supplementation prevented IgE-mediated OVA allergic responses, increased in gut permeability to allergens, and intestinal expression of inflammatory molecules.
Conflict of interest
No conflict to disclose.
This work was supported by grants from Korea Health, Ministry of Health and Welfare (A08-0664-AD1601-08N1-000208), Gang-won Regional Innovation Agency, Ministry of Knowledge Economy, and the Next-Generation BioGreen 21 Program (No. PJ008005), Rural Development Administration, Republic of Korea.
* Corresponding author. Tel.: +82 2 710 9395; fax: +82 2 7109453.
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0944-7113/S--see front matter [c] 2012 Elsevier GmbH. MI rights reserved. http://dx.doi.org/10.1016/j.phymed.2012.04.008
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Eun-Ju Lee (a), Min-Ji Song (b), Hye-Soon Kwon (c), Geun Eog Ji (d), (e), Mi-Kyung Sung (b), *
(a) Asan Institute for Life Science, Seoul 138-736, Republic of Korea
(b) Department of Food and Nutrition, Sookmyung Women's University, Seoul 140-742, Republic of Korea
(c) Food Safety Research Institute, Nonghyup, Seoul 100-707, Republic of Korea
(d) Department of Food and Nutrition, Research Institute of Human Ecology, Seoul National University, Seoul 151-742, Republic of Korea
(e) Research Center, BIFIDO Co., Ltd., Inc., Hongcheon 250-804, Republic of Korea
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|Author:||Lee, Eun-Ju; Song, Min-Ji; Kwon, Hye-Soon; Ji, Geun Eog; Sung, Mi-Kyung|
|Publication:||Phytomedicine: International Journal of Phytotherapy & Phytopharmacology|
|Date:||Jul 15, 2012|
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