• Title/Summary/Keyword: intranasal administration

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The Effects of Tongkwansan on the Changes of Total IgE and Specific IgE in Allergic Rhinitis Mouse Model (알레르기성 비염 모델에서 통관산(通關散)이 Total IgE, specific IgE 생산에 미치는 영향)

  • Lee, Seung-Joo;Kim, Yoon-Bum
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.20 no.1 s.32
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    • pp.16-26
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    • 2007
  • Background &Objectives : Rhinitis is an inflammation of nasal mucosa and the major symtoms are watery rhinorrhea, sneezing, itchy nose, and nasal obstruction. Rhinitis is classified into allergic rhinitis and nonallergic rhinitis. Allergic rhinitis is an immune reaction by allergen, and vasomotor rhinitis which is nonallergic and noninfectious is hypersensitive reaction. The incidence of allergic rhinitis has increased and the rate of vasomotor rhinitis is high. However there have been no studies about vasomotor rhinitis compared with allergic rhinitis. And there have been no studies so far performed on the effect of Tongkwansan. Therefore this study is aimed to find out the effects of Tongkwansan on allergic rhinitis and vasomotor rhinitis. Materials and Methods : Fifteen BALC/c mouses were divided into three groups : normal group, control group and sample group. To induce the allergic rhinitis in control group and sample group, mouses were sensitized intrapertioneally 0.1% ovalbumin solution three times at intervals of 1 week. Then intranasal sensitization was performed by diffusing 0.1 % ovalbumin solution 3 times at intervals of 2 days. After that time, mouses in the sample group were oral administration treated by Tongkwansan for 28 days. We observed changes in the segment of IL-4, IL-5, $IFN-{\gamma}$, Total IgE, and ovalvumin specific IgE in blood. We used the statistical methods of ANOVA test(p<0.05). Results : There were no significant changes statistically in $IFN-{\gamma}$, IL-4, and IL-5 in blood(p<0.05). There were also no significant changes statistically in Total IgE, OVA-specific IgE in blood(p<0.05). Conclusion : According to above results, it is supposed that Tongkwansan has no significant effects on allergic rhinitis. But it is supposed that Tongkwansan has significant effects on vasomotor rhinitis which is nonallergic and noninfectious

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The New Phytoformula Containing Morus alba, Schizandra sinensis and Asparagus cochinchinensis Inhibits Lung Inflammation in vitro and in vivo

  • Jeong, Hyeon Gun;Lee, Chan Woo;Lee, Ju Hee;Kim, So Joong;Kwon, Yong Soo;Heo, Yisu;Kim, Hyun Pyo
    • Natural Product Sciences
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    • v.22 no.1
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    • pp.70-75
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    • 2016
  • A phytoformula containing the root barks of Morus alba, the fructus of Schizandra sinensis and the roots of Asparagus cochinchinensis (MSA) was prepared as a potential new herbal remedy, and its therapeutic potential for alleviating inflammatory lung conditions was examined. For in vivo evaluation, an animal model of lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice was used. With oral administration of 6 - 60 mg/kg, MSA potently and dose-dependently inhibited bronchitis-like symptoms in acute lung injury induced by intranasal treatment of LPS as judged by the number of cells in the bronchoalveolar lavage fluid (BALF) and histological observation. The inhibitory potency was comparable with that of dexamethasone. For in vitro assay, the effects on the production of proinflammatory molecules in lung epithelial cells and alveolar macrophages were examined. Although MSA inhibited IL-6 production in IL-$1{\beta}$-treated lung epithelial cells (A549) only at a high concentration ($300{\mu}g/ml$), the formula strongly and concentration-dependently inhibited NO production in LPS-treated alveolar macrophages (MH-S) at $20-300{\mu}g/ml$. Based on all of these findings, the new phytoformula MSA is suggested to have the potential to control inflammatory lung diseases including bronchitis, at least in part, by inhibiting inducible nitric oxide synthase-catalyzed NO production.

Compound K ameliorates airway inflammation and mucus secretion through the regulation of PKC signaling in vitro and in vivo

  • Lee, Jae-Won;Kim, Mun-Ock;Song, Yu Na;Min, Jae-Hong;Kim, Seong-Man;Kang, Myung-Ji;Oh, Eun Sol;Lee, Ro Woon;Jung, Sunin;Ro, Hyunju;Lee, Jae Kyoung;Ryu, Hyung Won;Lee, Dae Young;Lee, Su Ui
    • Journal of Ginseng Research
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    • v.46 no.3
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    • pp.496-504
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    • 2022
  • Background: Cigarette smoke (CS) is considered a principal cause of chronic obstructive pulmonary disease (COPD) and is associated with mucus hypersecretion and airway inflammation. Ginsenoside compound K (CK), a product of ginsenoside metabolism, has various biological activities. Studies on the effects of CK for the treatment of COPD and mucus hypersecretion, including the underlying signaling mechanism, have not yet been conducted. Methods: To study the protective effects and molecular mechanism of CK, phorbol 12-myristate 13-acetate (PMA)-induced human airway epithelial (NCI-H292) cells were used as a cellular model of airway inflammation. An experimental mouse COPD model was also established via CS inhalation and intranasal administration of lipopolysaccharide. Mucin 5AC (MUC5AC), monocyte chemoattractant protein-1, tumor necrosis factor-α (TNF-α), and interleukin-6 secretion, as well as elastase activity and reactive oxygen species production, were determined through enzyme-linked immunosorbent assay. Inflammatory cell influx and mucus secretion in mouse lung tissues were estimated using hematoxylin and eosin and periodic acid-schiff staining, respectively. PKCδ and its downstream signaling molecules were analyzed via western blotting. Results: CK prevented the secretion of MUC5AC and TNF-α in PMA-stimulated NCI-H292 cells and exhibited a protective effect in COPD mice via the suppression of inflammatory mediators and mucus secretion. These effects were accompanied by an inactivation of PKCδ and related signaling in vitro and in vivo. Conclusion: CK suppressed pulmonary inflammation and mucus secretion in COPD mouse model through PKC regulation, highlighting the compound's potential as a useful adjuvant in the prevention and treatment of COPD.

Effect of CpG Oligodeoxynucleotides on Airways of Mice with Established Airways Inflammation (기도 염증이 유발된 생쥐에서 CpG Oligodeoxynucleotides가 미치는 효과)

  • Hwang, Hei-Won;Kim, Su-Jin;Kim, Won-Duk;Cho, Sung-Min;Lee, Dong-Suk;Choi, Sung-Min
    • Clinical and Experimental Pediatrics
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    • v.45 no.7
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    • pp.875-883
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    • 2002
  • Purpose : Airways eosinophilia and increased IgE, characteristic features of asthma, result from a predominant Th2 response. In this study, we investigated the effect of CpG oligodeoxynucleotides (ODNs) on the inhibition of airways eosinophilia in mice with established airway inflammation. We also investigated the immunological mechanisms involved. Methods : Groups of BALB/c mice were sensitized intradermally with ovalbumin(OVA). At week 10, airway inflammation was induced by intranasal challenge of the mice with OVA. At week 14, the mice were challenged intranasally again with OVA in the presence and without the presence of CpG ODNs. Mice with saline administration served as negative controls. Bronchoalveolar lavage fluids(BALF) were obtained and eosinophils were counted. Th1 and Th2 cytokines in the spleen cell cultures were measured by ELISA. Serum OVA-specific IgE and IgG2a antibodies were also measured by ELISA. Results : BALF eosinophils were significantly inhibited in the CpG ODNs-treated mice(P<0.01). IgE and IgG2a levels increased significantly in both CpG ODNs-treated and untreated groups as compared to the negative control group; there was, however, no significant difference between the two groups four days after intranasal administration of CpG ODNs. Cytokine analysis revealed decreased production of IL-4, IL-5, and IL-13 and increased production of IL-12 in the CpG ODNs-treated group as compared to the untreated group. Interestingly, $IFN-{\gamma}$ levels were not upregulated in the CpG ODNs-treated group. Conclusion : CpG ODNs vaccination is a potentially useful approach for reversing airways eosinophilia in mice with established airways inflammation.

The Effect of Tongkyu-tang on the Ovalbumin-inhalation Rat Model with Allergic Rhinitis (통규탕(通竅湯)이 알레르기 비염 모델 횐 쥐에 미치는 영향)

  • Jung, Jin-Young;Kim, Yoon-Bum
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.18 no.2
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    • pp.36-50
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    • 2005
  • Background and Objectives: Allergic rhinitis is an allergic reaction characterized by sneezingm itchy nose, mouth and throat, congestion and/or nasal discharge. The offending allergenes are usually pollens, molds, dust mites and animal allergen. Recently, the incidence of infectious nasal diseases tend to decrease. However, allergic rhinitis has increased and treatment in most cases has only deat with the symptom. Tongkyu-tang was composed of sixteen crude drugs. The Oriental Medical References mention therapeutic effects of Tongkyu-tang on nasal obstruction, watery nasal discharg. And Tongkyu-tang has clinically been used for the treatment of common cold, headache, sternutation, rhinitis etc. Speacially Tongkyu-tang is one of the most frequently used medical treatment for the allergic rhinitis. Experimental studies were conducted to investigate for the effect of Tongkyu-tang on the changes of neutrophil segment, lymphocyte, total IgE and nassal tissue in allergic rhinitis of ovalbumin-inhalation rat. Meterial and Methods: Fifteen Sprague-Dawley rats were divided into three group: normal group, control group, experimental group. To induce the allergic rhinitis in control group and experimental group, rats were sentitized intraperitoneally with 0.1 % ovalbumin solution 3 times at intervals of I week. Then intranasal sensitization was performed by diffusing 0.1 % ovalbumin solution 3 times at intervals of 2 days. After that time, rat in the experimental group were oral administration treated by Tongkyu-tang for 28 days. We observed changes in nasal tissue; changes in the number of white blood cell, red blood cell and total Ig E; also changes in the segment of neutrophil and lymphocyte in blood. And we observed the changes of AST, ALT of three group. We used anova test statistically. Result: The number of leucocyte remained unchanged between three group. The number of erythrocyte was increased in experimental group and control group when compared with the normal group. The segment of neutrophil, in blood was decreased in experimental group when compared with the control group but, that was not significant statistically(p<0.05). The promotion of lymphocyte in blood was significantly decreased in experimental group when compared with the Control group(p<0.05). Total IgE was decreased in experimental group when compared with the control group but, that was not significant statistically(p<0.05). The cilium be well preserved in experimental group: the nasal tissue in experimental group was similar to in the normal group. Congestion and expantion of grandular cell in nasal submucosa, hypertropy of epithelium in nasal mucosa, acid mucus in epithelium and neutral mucus in subepithelium were decreased in experimental group when compared with the control group. Effect of Tongkyu-tang on the liver function were also studies in rats. Treatment of Tongkyu-lang did not affected on AST and ALT. Conclusion: Considering the above experimental results, it is suggested that oral administration treatment using Tongkyu-lang, without worry about liver function injury, decreased response on an Animal model with Allergic Rhinitis.

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Attenuation of airway hyperreactivity and inflammation by Cheongsangbiyeum administration in a mouse model of asthma (마우스 천식모델에서 청상비음(淸上秘飮)의 기도 과민반응 및 염증의 억제 효과)

  • Kim, San;Sung, Byung-Gon;Lee, Sung-Jin;Lim, Kyu-Sang
    • 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.

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The effects of Socheongryong-Tang on LPS-induced lung inflammation rats model (소청룡탕이 LPS로 유도된 폐손상 동물모델에 미치는 영향)

  • Jin, Bo-Ram;Choi, In Young;Hwang, Do Young;Ham, Seong-Ho;An, Hyo-Jin
    • The Korea Journal of Herbology
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    • v.34 no.5
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    • pp.21-28
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    • 2019
  • Objectives : In present study, we investigated a therapeutic effect and optimum dose of Socheongryong-Tang (SCT) on LPS-induced lung inflammation rats model. Methods : Male Sprague-Dawley rats ($260{\pm}10g$) were divided into 12 groups : Group 1 included the normal rats, and Group 2-12 were administrated LPS by intranasal injection to induce experimental lung inflammation. After 1 day of LPS administration, Group 3-9 were treated with SCT ${\times}1/4$, ${\times}1/2$, ${\times}1$, ${\times}3$, ${\times}6$, ${\times}12$ or ${\times}18$, respectively. Group 10-12 (positive control) were treated with dexamethasone 1 mg/kg or acetylcystein 1.5 mg/kg or diclofenac sodium 0.4 mg/kg, respectively. After sacrifice, bronchoalveolar lavage fluid (BALF) was isolated. The levels of IL-$1{\beta}$, TNF-${\alpha}$, mucin glycoprotein 5AC (MUG5AC) were measured in BALF using enzyme-linked immunosorbent assay (ELISA). Results : LPS injected rats exhibited outstanding lung inflammation manifestations, including increased amount of total cells and neutrophil, and upregulated inflammatory cytokines level in BALF. However, the administration of SCT ${\times}1/4$, ${\times}1/2$ and ${\times}1$ decreased total cells and neutrophil, and suppressed the production of inflammatory cytokines, including $IL-1{\beta}$ and TNF-${\alpha}$, and MUG5AC in BALF. Notably, inhibitory effect of SCT ${\times}1/2$ and ${\times}1$ on the level of TNF-${\alpha}$ was markedly better than that of positive controls, dexamethasone and acetylcystein. Conclusions : Taken together, these results suggest that SCT ${\times}1/2$ and ${\times}1$ has therapeutic effects on LPS-induced lung inflammation rats model.

The Effects of $Hwangryunhaedok$-$tang$ Pharmacopuncture by the Anti-inflammatory Action of Suppression of iNOS Production on Mice with Allergic Rhinitis (황련해독탕 약침액의 iNOS 생성 억제를 통한 항염증효과가 알레르기성 비염 유발 생쥐의 치료에 미치는 영향)

  • Cho, Jae-Yong;Kim, Yu-Jong;Kim, Eun-Jung;Lee, Seung-Deok;Kim, Kap-Sung
    • Journal of Acupuncture Research
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    • v.29 no.1
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    • pp.89-101
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    • 2012
  • Objectives : The purpose of this study was find out the therapeutic effects of its exclusive use on the rat with allergic rhinitis. Materials and Methods : Thirty Sprague-Dawley rats were divided into three group : normal group, control group and sample group. To induce the allergic rhinitis in control group and sample group, rats were sensitized intraperitoneally with 0.1% ovalumin solution 3 times at intervals of 1 week. Then intranasal sensitization was performed by diffusing 0.1% ovalumin solution 3 times at intervals of 2 days. After that time, rats in the sample group were administered by $Yonghyang$($LI_{20}$) subcutaneously to treat the inflammation. Results : 1. The anti-oxidant effects of $Hwangryunhaedok-tang$ extract was dose-dependantly increased. 2. The RAW 264.7 cells were treated with LPS for 1 hours prior to the addition of indicated concentrations ($0.4,-1.0mg/m{\ell}$) of HHT, and the cells were further incubated for 24 hours. The LPS-induced iNOS mRNA expression and NO production were dose-dependantly decreased in HHT treated RAW 264.7 cells. 3. The number of eosinophil in HP noticeably decreased than CON and this decrease had probability. The infiltration of eosinophil in HP noticeably decreased than CON. 4. The damaged mucosa as disruption of cilia in respiratory cell and vacant mucose secreting cell were increased CON, but HP same as normal configuration. Decrease of PAS positive cell were shown in CON, but goblet cell occupied with neutral mucous were shown in HP. Decrease of mucosal stress(HSP70). Decrease of perennial sign(PPAR-${\gamma}$). Decrease of icthing and sneezing intricate neurotransmitter-(substance P). 5. The anti-inflammation of HHT pharmacopuncture for AR caused mucosa comes to result as belows. Decrease of pre-inflammation cytokine(TNF-${\alpha}$). Decrease of transcription factor (NF-${\kappa}B$ p65). Decrease of transcription factor inhibitor(p-$I{\kappa}B$). Decrease of inflammation cytokine(iNOS). Conclusions : The results may suggest that administration treatment using $Hwangryunhaedok-tang$ pharmacopucnture decreases the inflammatory response on an animal model with allergic rhinitis.

Pharmacokinetic Preformulation Study of rH IL-2 (인터루킨-2의 제제설계를 위한 체내 동태학적 연구)

  • Seo, Min-Seok;Shim, Chang-Koo;Kwon, Jong-Bum;Na, Do-Sun;Lee, Sun-Bok;Hahm, Kyung-Soo;Han, Moon-Hi
    • YAKHAK HOEJI
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    • v.34 no.4
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    • pp.238-243
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    • 1990
  • Pharmacokinetic characteristics of recombinant human interleukin-2 (rH IL-2) wre studied in the rat. First, different doses of rH IL-2 ranging from 6,400 to 1,600,000 U/kg were injected intravenously and the effect of dose size on the pharmacokinetics was examined. There was no dose dependency in the pharmacokinetics of rHIL-2 in the dose range of 6,400-40,000 U/kg. But at the dose of 1,600,000 U/kg, there was a severe hemolysis throughout the experiment and the pharmacokinetic parameters such as Vdss and CLt were significantly increased compared to those obtained from lower doses. It also showed that this drug is hardly distributed to the peripheral tissues and hardly eliminated from the body, since the valume of distribution (Vdss) and total body clearance (CLt) were 45-75 ml/kg and 1-2 ml/min/kg, respectively. The Vdss is close to the actual plasma volume and the CLt is less than glomerular filtration rate (GFR). Therefore it seemed that rH IL-2 is distributed only in the plasma pool and hardly filtered in the kidney due to its very large molecular weight. Second, rH IL-2 was administered to the rat via several routes such as hepatic portal vein (PV), intraperitoneal (IP), peroral (PO) and intranasal (IN) routes. The bioavailabilities (BA) of PV, IP, PO and IN routes were 96.8, 4.9, 0 and 0.1%, respectively. The addition of some nasal absorption enhancers such as taurocholate, taurodeoxycholate, glycocholate and glycodeoxycholate did not increase the BA of intranasaly administered rH IL-2. The result is contrast to the effect of these bile salts on the nasal absorption of ${\alpha}-inteferon$. Considering it together with the pharmacokinetic parameters, very large molecular weight of rH IL-2 seemed again to be the cause to very poor membrane permeability.

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The Effect of the Bojungikgi-tang in a Mouse Model of Allergic Rhinitis (포중익기탕(補中益氣湯)이 알레르기 비염(鼻炎) 유발 마우스에 미치는 효과(效果))

  • Kim, Sun-Min;Sim, Sung-Youn;Byun, Hak-Sung;Kim, Kyung-Jun
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.18 no.3
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    • pp.26-36
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    • 2005
  • Objectives: Maier symptoms of allergic rhinitis are nasal obstructions, sneezing and watery rhinorrhea. When exposed to certain allergens, the IgE covered mast cells degranulate and release inflammatory mediators and cytokines which result in a local inflammatory reaction. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of allergic rhinitis. This experimental study was done to reveal the effects of the Bojungikgi-tang on the allergic rhinitis. We have studied effect of mice on OVA-induced production of IL-4, IL-5, $INF-{\gamma}$ by murine splenocytes and effect of OVA-induced Total IgE and OVA-specific IgE Meterial and Metheds: 21 BALB/c rats were divided into three groups: normal group, control group, experimental group. To induce the allergic rhinitis in control group and experimental group, rats were sentitized intraperitioneally with 0.1% ovalbumin solution 3 times at intervals of 2 weeks. Then intranasal sensitization was performed by diffusing 0.1% ovalbumin solution 3 times at intervals of 2 days for a week. After that time, rats in experimental group were oral administration treated by the Bojuogikgi-tang fer 28 days. We observed changes of IL-4, IL-5, $INF-{\gamma}$, Total IgE and OVA-specific IgE. We used independent-test statistically. Results: 1. In IL-4 study, Bojungikgi-tang treated group didn't show significant differences. 2. In IL-5 study, Bojungikgi-tang treated group shows significant differences. 3. In $INF-{\gamma}$ study, Bojungikgi-tang treated group shows significant differences. 4. In Total IgE, Bojungikgi-tang treated group shows significant differences. 5. In OVA-specific IgE, Bojungikgi-tang treated group didn't show significant differences. According to this result, Bojungikgi-tang was concluded to be effective on lowering the total IgE. Through this. Bojungikgi tang seems to reduce the symptoms of allergic rhinitis. More studies are required to know exact mechanism of Bojungikgi tang to show the anti allergenic effect.

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