• Journal of Microbiology and Biotechnology
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• v.28 no.1
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• pp.65-76
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• 2018

Although there has been a steady increase in the prevalence of food allergies worldwide in recent decades, no effective therapeutic strategies have been developed. Modulation of the gut microbiota composition and/or function through probiotics has been highlighted as a promising target for protection against food allergies. In this study, we aimed to investigate the allergy-reducing effects of a probiotic mixture (P5: Lactococcus lactis KF140, Pediococcus pentosaceus KF159, Lactobacillus pentosus KF340, Lactobacillus paracasei 698, and Bacillus amyloliquefaciens 26N) in mice with ovalbumin (OVA)-induced food allergy. Administration of P5 significantly suppressed the oral OVA challenge-induced anaphylactic response and rectal temperature decline, and reduced diarrhea symptoms. Moreover, P5 also significantly inhibited the secretion of IgE, Th2 cytokines (interleukin (IL)-4, IL-5, IL-10, and IL-13), and Th17 cytokines (IL-17), which were increased in mice with OVA-induced food allergy, and induced generation of CD4+Foxp3+ regulatory T cells. These results revealed that P5 may have applications as a preventive agent against food allergy.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.1
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• pp.81-89
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• 2018

This study evaluated the anti-asthmatic activities of 2,6-di-tert-butyl-4-hydroxymethylphenol (DBHP) that is a potent phenolic antioxidant in edible vegetable oil. The effects of DBHP on bronchial asthma were evaluated by determining the specific airway resistance (sRaw) and tidal volume (TV) during the immediate asthmatic response (IAR) and the late-phase asthmatic response (LAR) in guinea pigs with aerosolized ovalbumin-induced asthma. Recruitment of leukocytes and the levels of biochemical inflammatory mediators were determined in the bronchoalveolar lavage fluids (BALFs), and histopathological surveys performed in lung tissues. DBHP significantly inhibited the increased sRaw and improved the decreased TV on IAR and LAR, and also inhibited recruitment of eosinophils and neutrophils into the lung, and release of biochemical inflammatory mediators such as histamine and phospholipase $A_2$ from these infiltrated leukocytes, and improved pathological changes. However, anti-asthmatic activities of DBHP at oral doses of 12.5 to 50 mg/kg was less than those of dexamethasone (5 mg/kg, p.o.) and cromoglycate (10 mg/kg, p.o.), but more potent or similar to that of salbutamol (5 mg/kg, p.o.). These results in the present study suggest that anti-asthmatic effects of DBHP in the guinea pigs model of OVA-induced asthmatic responses principally are mediated by inhibiting the recruitments of the leukocytes and the release of biochemical inflammatory mediators from these infiltrated leukocytes.

• Biomolecules & Therapeutics
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• v.16 no.4
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• pp.299-305
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• 2008

Active cardiovascular anaphylactic response was induced in ovalbumin-sensitized, pithed Sprague-Dawley and Wistar rats. On intravenous administration of the antigen, ovalbumin, marked tachycardia and pressor responses were immediately elicited. Thereafter, a delayed long-lasting severe hypotensive response was observed. These anaphylactic cardiovascular responses were maximal 2-3 weeks after the sensitization, and the response was slightly diminished 6 weeks after sensitization. The immediate pressor response was blocked by a non-selective serotonin antagonist methysergide at a dose-dependent manner, but not by histamine receptor antagonists mepyramine (pyrilamine) or cimetidine. The delayed hypotension was reduced either by histamine $H_1$ receptor antagonist mepyramine or $H_2$ receptor antagonist cimetidine, both in a dose-dependent manner. The tachycardic response was not influenced by serotonin or histamine receptor antagonists examined in this study. Differently from the cardiovascular responses, there was no observable bronchial contraction in Sprague-Dawley rat trachea in contrast to Wistar rat where the trachea contracted to in vitro antigen challenge. The cardiovascular anaphylactic model seems to be useful for studying cardiovascular events that occur exclusively in peripheral heart-blood vessel systems. The involvement of two major anaphylactic mediators, serotonin and histamine, is partially demonstrated.

• Journal of Korean Medicine Rehabilitation
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• v.24 no.3
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• pp.71-85
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• 2014

Objectives In this study, we investigated the inhibitory effects of Samhwangsasim-tang (S.H) on the allergic response caused by ovalbumin(OVA) sensitization and challenge in BALB/c mice. Methods The experimental animals were divided into five groups; 1) normal as negative control, 2) OVA-sensitized mice, 3) OVA-sensitized mice treated with 200 mg/kg of S.H 200, 4) OVA-sensitized mice treated with 400 mg/kg of S.H 400, and 5) OVA-sensitized mice treated with 5 mg/kg of Dexamethasone (Dex). Antigen sensitization for allergic mouse model was performed with twice injection of OVA for 2 weeks. After secondary injection, S.H was administrated orally into mice every day for 13 days and the inhibitory effect of S.H on allergic responses was evaluated. Results Treatment of S.H into allergic mice reduced significantly ear edema and infiltration of immune cells in ear tissues induced with OVA challenge in a dose-dependent manner. S.H reduced significantly the serum levels of Total Immunoglobulin(Ig)G and IgE, and particularly inhibited the production of OVA-specific IgE, but not OVA-specific IgG. The serum level of proinflammatory cytokine TNF-${\alpha}$ and Th2-associated cytokine IL-4 also were significantly decreased by S.H adminstration in a dose denpendent manner. S.H attenuated OVA-induced secretion of IFN-${\gamma}$, but not IL-12 which is a cytokine inducing the development of Th1 cells. It also reduced significantly the secretion of IL-4, which is a cytokine inducing the development of Th2 cells, after splenocytes were stimulated with OVA. However the secretion of IL-5 and IL-13 was influenced weakly or a little. Conclusions These results indicate that S.H could reduce the allergic response through inhibition of antigen-specific IgE and Th2-inducing cytokines. It suggest that S.H may be available clinically for the treatment of allergic patients.

• Korean Journal of Oriental Medicine
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• v.5 no.1
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• pp.1-15
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• 1999

Chronic asthma is considered as an incurable disease in modern society. This study focused on development of an animal model for the chronic asthma to investigate new drugs from traditional herbal medicine. And we tested the animal model with a typical prescription, Chungsangboha-tang and tried to find biochemical markers such as catecholamines and cAMP in serum, and as densities of beta-receptor in lung tissues. SD rats were actively sensitized by exposure to ovalbumine (OA). Ten days after sensitization, rats were challenged with OA aerosol by nebulizer six times every three days. Mucin was increased in bronchoalveolar lavages (BALs) after antigen (OA) challenge. Serum concentration of epinephrine was decreased significantly although there were not changed much in serum concentration of cAMP and the densities of beta-receptor in lung tissues. Chungsangboha-tang (5 g/kg/day) was given orally to ovalbumin-sensitized rats (n=8) for 15 days. Mucin in bronchoalveolar lavages (BALs) was increased significantly after treatment of Chungsangboha-tang although concentrations of epinephrine and cAMP were not changed significantly. The densities of beta-receptor in lung tissues were not different from those of controls. These results suggest that the ovalbumin-sensitized rats can be a good animal model of chronic asthma and Chungsangboha-tang is a possible drug in the treatment of chronic asthma.

• Tuberculosis and Respiratory Diseases
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• v.48 no.1
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• pp.33-44
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• 2000

Background: To evaluate airway responses and inflammation to antigen in Sprague-Dawley rat asthma model, we examined airway responses, serial histologic changes of the lung, and the relationship between airway responses and airway inflammation after antigen airway challenge. Methods: Sprague-Dawley rats were sensitized with subcutaneous injection of 10 ${\mu}g$ ovalbumin(OA). Antigen airway challenges were done 14~16 days after sensitization and the sensitized rats were sacrificed 1h($A_E$), 6~8h($A_L$) and 1day($A_D$) after airway challenge, to examine the histologic changes of the lung. Airway responses were measured by body plethysmograph and recorded by enhanced pause(Penh) as an index of airway obstruction 6~8h after antigen challenges. Nonsensitized controls(10 rats) were also challenged with antigen and sacrificed 1 day later. Histopathologic examination of two trachea, large bronchi, small bronchi, and vessels was performed to evaluate the severity of inflammation and eosinophilic infiltration with H&E stain. Results: In 17 of 20 rats(85%) in both groups, we observed airway responses. Among them, an early response(ER) in 15 rats(75%), an dual response in 5(25%), and an late response(LR) only in 2 rats(10%) displayed. There were no significant differences in the severity of inflammation among the trachea, large bronchi, small bronchi and vessels in all groups after antigen challenge(p>0.05) and between early and late responders. The significant eosinophil infiltration was observed in 5 rats(50%) of AL(p<0.05) compared with in AE and controls. Also, eosinophil infiltration was observed in higher trend in LR(57.1%) compared to ER(40%)(p>0.05). Conclusion: Sprague-Dawley rats sensitized with subcutaneous injection of OA showed a significant airway responses to antigen challenge. But antigen challenges caused a little eosinophil infiltration and no significant airway inflammation. Asthma model of Sprague-Dawley rats could be useful for antigen-induced airway responses, but this model has a limitation for the study of human asthma because of no significant pathologic change.

• Biomolecules & Therapeutics
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• v.16 no.3
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• pp.237-242
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• 2008

The effect of Picrorrhiza Rhizoma (PR) aqueous extracts were evaluated on 2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis, type I allergic model. Contact dermatitis was induced by sensitization with dinitrophenyl-derivatized ovalbumin (DNP-OVA) and DNFB challenge as antigen. Three different concentrations of PR extracts (300,150 and 75mg/kg) were orally administered to DNP-OVA sensitization mice once a day for 7 days with reference materials; dexamethasone (15mg/kg, intraperitoneal treatment). End of 7 days oral administration of PR extracts or intraperitoneal treatment of dexamethasone, the changes on the edematous changes and scratching behavior were measured. Immediate after DNFB challenge on ear or paw of DNP-OVA sensitized mice, increases of ear and paw thicknesses and weights were detected with anterior ear skin (dermis to epidermis) thickness and paw scratching behavior increases. However, these DNFB-induced increases on ear and paw thicknesses, weights and scratching behaviors were decreased by treatment of all three different dosages of PR extracts and dexamethasone, respectively. In addition, the increases of anterior skin thicknesses were also dramatically inhibited by treatment of all three different dosages of PR extracts and dexamethasone at histopathological observations. The results obtained in this study suggest that oral treatment of PR extracts also has relatively favorable effects on allergic dermatitis.

• Toxicological Research
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• v.26 no.2
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• pp.123-130
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• 2010

The effect of DHU001, a mixed herbal formula consisted of 7 types aqueous extracts for various respiratory disorders were evaluated on 2,4-dinitrofluorobenzene (DNFB)-induced contact dermatitis, type I allergic model. Contact dermatitis was induced by sensitization with dinitrophenyl-derivatized ovalbumin (DNP-OVA) and DNFB challenge as antigen. Two different dosages of DHU001 (300 and 150 mg/kg) were orally administered to DNP-OVA sensitization mice once a day for 7 days with reference material, dexamethasone (15 mg/kg, intraperitoneal treatment). End of 7 days oral administration of DHU001 extracts or intraperitoneal treatment of dexamethasone, the changes on the edematous changes and scratching behavior were measured. Immediate after DNFB challenge on ear or paw of DNP-OVA sensitized mice, increases of ear and paw thicknesses and weights were detected with anterior ear skin (dermis to epidermis) thickness and paw scratching behavior increases. However, these contact dermatitis signs induced by DNFB treatment were reduced by treatment of the both different dosages of DHU001 and dexamethasone, respectively. The results obtained in this study suggest that oral treatment of DHU001 extracts also has relatively favorable effects on contact dermatitis.

• Journal of Pharmaceutical Investigation
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• v.41 no.6
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• pp.355-362
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• 2011

This work was performed to investigate the protective effect of ethanol extract (AEx) from acorn (Quercus acutissima CARR.) against allergic mediated responses in asthma model cells and mice. The AEx inhibited antigen-stimulated cytokine production such as interleukin (IL)-4, IL-13 and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and AEx also inhibited intracellular reactive oxygen species (ROS) generation against IgE-mediated allergic response in rat basophilic leukaemia RBL-2H3 cells. The ovalbumin (OVA)-sensitized mice were orally administered with AEx (100 or 300 mg/kg) and authentic tannic acid (75 mg/kg) every day for 15 days. Increased TNF-${\alpha}$ production by OVA-sensitization/challenge was significantly reduced by administration of AEx. The serum triglyceride levels of asthma mice were significantly reduced after feeding for 15 days with tannic acid or AEx. The mice fed with tannic acid or AEx also exhibited a significant reduction in body weights compared to those of asthma control group. The AEx increased the heme oxygenase (HO)-1 mRNA expression in the asthma model mice and showed DPPH radical scavenging activity. These results indicate that AEx protects against IgEmediated allergic and OVA-induced asthmatic responses via direct and indirect antioxidant activities. Reduced triglyceride and body weights may provide additional protective benefits of AEx on allergic asthma.

• Toxicological Research
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• v.18 no.2
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• pp.205-213
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• 2002

This study was undertaken to develop a subacute murine model for predicting occurrence of systemic anaphylaxis and to evaluate efficacy of various immunological parameters as the monitoring indices for the occurrence of anaphyalxis. The murine anaphyalxis model was developed through intraperitoneally sensitizing 100 $\mu\textrm{g}$ ovalbumin (OVA) in the presence of 1 mg alum and 300 ng cholera toxin twice a week interval followed by challenging 500 $\mu\textrm{g}$. OVA intravenously. Typical anaphylaxis symptoms were demonstrated at the both BALB/c mice, a strain prone to type-2 response, and C57BL/6 mice. a strain prone to type-1 response. Level of plasma histamine was approximately 50-fold or 30-fold higher in the mice sensitized with OVA than the mice sensitized with alum plus cholera toxin or the saline-treated mice after OVA challenge, respectively. Sensitization and challenge with OVA significantly enhanced plasma leukotriene $B_4$ level but not IgE levels in comparison with the control mice, which indicated the role of leukotriene $B_4$ for progression of anaphyalxis. Furthermore, among mice suffered from anaphylaxis, levels of OVA-specific IgGl were significantly higher in the BALB/c mice than in the C57BL/6 mice, which implied the genetic susceptibility for the induction of systemic anaphylaxis. Conclusively, simultaneous evaluation of histamine, leukotriene $B_4$, and allergen-specific IgG isotype may serve as more efficient monitoring tool for vaccine-related anaphyalxis.