• The Korean Journal of Physiology and Pharmacology
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• v.25 no.6
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• pp.555-564
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• 2021

We investigated the effects of naringenin and morin on IL-5 and ROS production in PMA+ionomycin-treated EL-4 cells with the corroboration of their antioxidant and anti-inflammatory properties using an asthma-induced mouse model. The EL-4 cell line was used to study the outcomes of naringenin or morin, followed by cell viability studies. Western blot analysis and ELISA test were used to determine Th2 mediated cytokines. In vivo studies were carried out on BALB/c mice to induce allergic asthma using ovalbumin administered intraperitoneally. Intracellular ROS was determined using 2',7'-dichlorodihydrofluorescein diacetate, followed by serum enzymatic (AST and ALT) estimations and inflammatory cell count in the bronchoalveolar lavage fluid (BALF) and lung tissues. Histopathological studies were conducted to examine lung tissue-stained architecture. Our findings suggested that naringenin and morin significantly suppressed IL-5 and ROS production via various pathways. Interestingly, by reducing NFAT activity, naringenin and morin stimulated HO-1 expression, thereby suppressing IL-5 secretion due to regulating the transcription factor Nrf2 via P13/Akt or ERK/JNK signalling pathways in EL-4 cells, demonstrating the involvement of HO-1 expression in inhibiting asthmatic inflammation. The increased inflammatory cells in the BALF were substantially decreased by both naringenin and morin, followed by inhibition in the elevated Th-2 cytokines levels. The TNF-α protein levels in an allergic asthma mouse model were significantly reduced by suppressing Akt phosphorylation and eosinophil formation. Recent findings confirmed that naringenin and morin possess the potential to control asthma-related immune responses through antioxidant and anti-inflammatory properties, indicating potential therapeutic agents or functional foods.

• The Korea Journal of Herbology
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• v.32 no.6
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• pp.55-62
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• 2017

Objectives : This study aims to evaluate the effects of natural herb mixutre (NHM) on atopic dermatitis and skin regeneration using in vivo test. Methods : NHM was prepared with DW. 25% of NHM was applied to skin lesion, where atopic dermatitis was induced by DNCB in NC/Nga mice. The levels of cytokines (IL-4, IL-5, IL-6, IL-13, TNF-a, and $IFN-{\gamma}$), and IgE in serum were measured by Luminex. Immune cells (WBC, eosinophil, lymphocyte, and monocyte) in blood were counted by coulter counter. The gross investigation of atopic dermatitis index score test were performed during the NHM treatment period. Also, the histopathological change of dorsal skin was observed by H&E and M&T staining. Results : NHM showed the levels of IL-4, IL-5, IL-6, IL-13, IgE, WBC, eosinophil, lymphocyte, and monocyte in serum or blood were significantly decreased. On the contrary, the productions of FGF, and VEGF were increased in the serum. Also, atopic dermatitis index score in NHM-treated mice were observed in the similar levels to those of normal group. Histological examination demonstrated that NHM suppressed immune cell infiltration and thickening of epidermis, meanwhile the extraction induced collagen production in the dorsal skin. Conclusion : This study demonstrated that NHM is appeared to be effective on atopic dermatitis and skin regeneration efficacy based on the observations with hematologic, gross, and histologic examinations. Therefore, we suggest that NHM could be effectively used as an external therapeutics against atopic dermatitis and a consequence skin damage.

• Korean journal of aerospace and environmental medicine
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• v.24 no.2
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• pp.21-27
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• 2014

We aimed to study about the effect of acute hyper-gravity (HG) on the allergic immune response in a murine model of allergic asthma. Thirty-two BALB/c mice were used. In Group A (control group, n=8), mice were sensitized and challenged with saline. Group B (HG control group, n=8) were exposed to HG (10 Gz, 1 hour) after intraperitoneal and intranasal saline challenge. Group C (asthma group, n=8) received intraperitoneal and intranasal ovalbumin (OVA) challenge. Group D (HG asthma group, n=8) were exposed to HG after intraperitoneal and intranasal OVA challenge. We evaluated serum total and OVA-specific IgE; serum titers of cytokines; and histopathologic examination of lung. As a result, titers of Serum total and OVA-specific IgE were not significantly different between groups. Compared to Group C, mice in Group D showed significant increase of Th2 cytokines (IL-4, IL-13), cytokines involved in eosinophilia (IL-3, IL-5, GM-CSF) and those involved in cell-medicated immunity (IFN-γ). In histopathologic examination, lungs of Group D showed significantly more infiltration of inflammatory cells compared to Group C. However, these differences were not so significant between Groups A and B. In conclusion, acute HG could exacerbate allergic asthma in experimental animals.

• Korean Journal of Medicinal Crop Science
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• v.20 no.2
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• pp.129-135
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• 2012

The feature of asthma are airway inflammation (AI), reversible airway obstruction, and an increased sensitivity to bronchoconstricting agents, elevated airway hyperresponsiveness (AHR), excess production of Th2 cytokines, and eosinophil accumulation in the lungs. This study was performed to investigate if oral administration of $Scutellaria$ $baicalensis$ Georgi water extracts (SBG) have the antiasthmatic potential for the treatment of asthma. Asthmatic HI and AHR were induced by systemic sensitization to ovalbumin (OVA) with intratracheal instillation with 0.1 mg/mL of diesel exhaust particles (DEP) suspension once a week for 10 weeks in BALB/c mice. SBG was orally administered with the concentraion of 200 mg/kg 5 days a week for 10 weeks. Long-term SBG treatment suppressed the eosinophil infiltration into airways from blood, the asthmatic AI and AHR by attenuating the production of cytokine IL-4, IL-5 and IL-13, histamine and OVA-specific IgE. Our data suggest that SBG has inhibitory effects on AI and AHR in a mouse model of asthma, may act as a potential Th2 cytokine antagonist, and may have a therapeutic effect on allergic asthma.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.19 no.2
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• pp.1-18
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• 2006

Objective : Although management of asthma has become increasingly effective, its cure remains elusive, necessitating a new modality to prevent or eliminate causes triggering clinical progress. Based in the clinical experiences, a novel decoration Cheongsangbiyeum (CSB), has been developed to treat asthma, which consists of Polyporus, Semen Myristicae, Pericarpium citri Reticulatae, Rhizoma Cimicifugae, Cortex Albizziae, Fructus Rubi, Rhizoma Zedoariae, and Rhizoma Rhei. In the current study, its anti-asthmatic efficacy was evaluated using a mouse model of asthma. Methods : Experimental allergic asthma was induced by repeated intraperitioneal sensitization and intranasal challenge of ovalbumin (OVA). Water extract of CSB (1 mg/mouse/day) was administrated orally whereas control mice on given with identical volume of phosphate-buffered saline (PBS) for 5 days during the course of antigen challenge. When airway hyperreactivity(AHR) measured by ${\bata}-methacoline-induced$ airflow obstruction was compared, AHR of CSB-treated mice was significantly lower than those of control mice, indicating that CM extract can attenuate an asthmatic symptom. Airway recruitment of leukocytes and eosinophils was also markedly reduced by CSB treatment suggesting that oral treatment of CSB can alleviate the airway inflammation. For a better understanding of possible mechanisms underlying anti-asthmatic effet of CSB, cytokine (IL-4, IL-5, IL-13 and $IFN{\gamma}$ levels in bronchoalveola lavage fluid (BALF) and lung tissues were determined. Results : The results showed that cytokine levels were significantly lowered by CSB treatment. Additionally, number of draining lymph node cells was significantly lower than those of control mice. These data indicate that CSB suppress in vivo allergen-specific response. However, notably, levels of type 2 cytokines such as IL-5 and IL-13 were more profoundly influenced. Moreover, in vitro OVA-specific proliferative response and type 2 cytokine (IL-4, IL-5 and IL-13) production lymph node cells was markedly decreased in CSB-treated mice, whereas their $IFN{\gamma}$ production was not significantly altered Thrse data clearly showed a preferential inhibition of type 2 T cell (Th2) response by CSB treatment. This finding was also supported by serum antibody data showing that levels of OVA-specific type 2 antibodies, IgE and IgG1, in CSB-treated mice were significantly lower than in control mice, while type 1 antibody, IgG2a level m rather higher than controls, although the difference was in significant. Conclusions : In conclusion, oral administration of CSB attenuates asthmatic manifestations including AHR ad airway recruitment of eosinophils in a mouse model which possibly results from selective inhibition of Th2 cell response to allergen. Our data suggest a potential clinical application of CSB for control of allergic asthma.

• IMMUNE NETWORK
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• v.22 no.2
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• pp.20.1-20.9
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• 2022

Despite the high prevalence of chronic dermatitis and the accompanied intractable itch, therapeutics that specifically target itching have low efficacy. Increasing evidence suggests that TLRs contribute to immune activation and neural sensitization; however, their roles in chronic itch remain elusive. Here, we show that the RBL-2H3 mast cell line expresses TLR4 and that treatment with a TLR4 antagonist opposes the LPS dependent increase in mRNA levels of Th2 and innate cytokines. The pathological role of TLR4 activation in itching was studied in neonate rats that developed chronic itch due to neuronal damage after receiving subcutaneous capsaicin injections. Treatment with a TLR4 antagonist protected these rats with chronic itch against scratching behavior and chronic dermatitis. TLR4 antagonist treatment also restored the density of cutaneous nerve fibers and inhibited the histopathological changes that are associated with mast cell activation after capsaicin injection. Additionally, the expression of IL-1β, IL-4, IL-5, IL-10, and IL-13 mRNA in the lesional skin decreased after TLR4 antagonist treatment. Based on these data, we propose that inhibiting TLR4 alleviated itch in a rat model of chronic relapsing itch, and the reduction in the itch was associated with TLR4 signaling in mast cells and nerve fibers.

• Journal of Physiology & Pathology in Korean Medicine
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• v.31 no.5
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• pp.277-283
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• 2017

Activated T helper 2 (Th2) immune function is hallmark of various allergic diseases. We investigated the anti-allergic effect of Jagamcho-tang extract(JE) on ovalbumin(OVA)-induced atopic dermatitis mice model and OVA-stimulated splenocytes isolated from the mice. Mice were intraperitoneally injected OVA/alum solution 2 times at interval of 14 days, followed by oral administration of JE for 7 days. After administration, mice were subcutaneously injected with OVA in ear. JE treatment reduced ear swelling and infiltration of inflammatory cells in ear. Serum levels of interleukin(IL)-4 and immunoglobulins, such as total-IgE and OVA-specific IgE, were decreased in JE treated group. Furthermore, JE treatment decreased OVA-induced Th2-associated cytokines like IL-4, IL-5 and IL-13 mRNA levels in splenocytes. In conclusion, JE reduced allergic immune response via IgE production and Th2 response in OVA-sensitized mice, suggesting that JE could be useful prescription for allergic diseases including atopic dermatitis.

• The Korea Journal of Herbology
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• v.24 no.2
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• pp.39-48
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• 2009

Objectives : To clarify the possible effect of JS (Juglans sinensis), PCF (Psoralea corylifolia L.), and J+P(JS+PCF), we examined their influence on the development of pulmonary eosinophilic inflammation in the asthmatic murine model. Methods : All mice were immunized on two different days (21 days and 7 days before inhalational exposure) by intraperitonial injections of 0.2 ml alum-precipitated Ag containing 100 ${\mu}$g of OVA bound to 4 mg of aluminum hydroxide in PBS. Seven days after the second sensitization, mice were exposed to aerosolized ovalbumin for 30 minutes/day on 3 days/week for 8 weeks (at a flow rate of 250 L/min, 2.5% ovalbumin in normal saline) and, JS, PCF and J+P (200 mg/kg, 400 mg/kg) were orally administered 3 times per week for 8 weeks. Results : The suppressive effects of JS, PCF, and J+P were demonstrated by the accumulation of eosinophils into airways, with the reduction of eosinophils and lung leukocytes. These were correlated with the marked reduction of IL-4, IL-5, IL-13 levels in the BALF and serum. OVA-specific IgE levels were also decreased in serum and BAL from these mice. And also JS, PCF, and J+P decreased eosinophilic CCR3 and CD11b expression in lung tissue. Conclusions : These results indicate that JS, PCF, and J+P have deep inhibitory effects on airway inflammation and hyper-responsiveness in the asthmatic murine model. The suppression of IL-5, IgE, and eosinophilils and the increase of IFN-${\gamma}$ production in BALF seem to contribute to these effects. Specially, esosinophils and TNF-a in J+P combination group were significantly reduced in BALF and lung tissue. Hence, the results indicated that JS, PCF, and J+P could act as an immuno-modulator which possesses anti-inflammatory and anti-asthmatic property by modulating the imbalance between Th1 and Th2 cytokines.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.27 no.3
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• pp.96-105
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• 2014

Objective : Glycyrrhiza uralensis Fisch (GUF) has been used as remedy of allergic diseases for a long time in Korea. In the present study, we investigated the anti-allergic effects of GUF on experimental allergic asthma mouse model using ovalbumin (OVA). Methods : BALB/c mice were sensitized and challenged with 100 ug of OVA and 1 mg of aluminum potassium sulfate of 0.2 ml phosphate-buffered saline (PBS) intraperitoneally on day 1 and 15. Mice were challenged on 3 consecutive days with 5% OVA and AHR was assessed 24 hrs after the last challenge. We examined total inflammatory cell number in bronchoaveloar lavage fluid (BALF), Th2-associated cytokine productions and lung histology. Results : GUF potently inhibited the development of airway hypersensitivity and also reduced the number of BAL cells during OVA-induced allergic asthma. GUF also inhibited cytokine productions such as IL-4, IL-13 in lung tissue. Furthermore, GUF treatment inhibited allergic airway inflammation. Conclusion : These results suggest that GUF may inhibit the production of IL-4, IL-13 and infiltration of inflammatory cell and be beneficial oriental medicine for allergic asthma.

• The Korea Journal of Herbology
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• v.24 no.4
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• pp.215-224
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• 2009

Objectives : Atopic dermatitis is a chronic inflammatory disease characterized by typically distributed eczematous skin lesion with pruritus, lichenification and dry skin. In this study, we performed to assess the therapeutic effects of co-treatment of Chenilyeomgamibang (CGB) and Chenggihaedok-san (CHS, C&C) on the TNCB(trinitrochlorobenzene)-induced atopic dermatitis in NC/Nga mice, characterized by the onset of atopic dermatitis along with an increase the number of inflammatory cells and dysregulation of Th2 cytokines. Methods : Defined amount of CGB was sprayed on mice skin and CHS was simultaneously orally administrated to TNCB treated NC/Nga mice for 5 weeks. The immune cell types were caracterized by flow cytometry using each specific antibody. The amount of Th2 cytokines in serum and splenocytes culture supernatant were measured by ELISA. Results : Administration of C&C significantly reduced clinical dermatitis severity including pruritus, edema, eczematous and erythema. Histological findings indicated that the thickening of epidermis/dermis and dermal infiltration of inflammatory cells were dramatically reduced. Flow cytometry analysis showed that infiltrated immune cell numbers of CCR3+, B220+/IgE+, Gr-1+/CD11b+, and CD117+ were significantly reduced in C&C-treated dorsal skin lesion. Furthermore, T cell composition rate in PBMC was also dramatically decreased by the treatment. C&C greatly down-regulated production of Th2 cytokines including IL-4, IL-5, IL-13 in the serum. The down- regulatory effects of C&C on these Th2 cytokines production were also detected in CD3/ CD28 activated splenocytes. Conclusions : These results indicated that C&C is a plausible therapeutic agent for treatment of atopic dermatitis through regulating the Th2 skewed immune system.