The Effects of Aromatherapy using Mask on Allergic Rhinitis symptoms, Fatigue, Quality of Life related to Allergic rhinitis In COVID-19 era

Her, Ji Hoo 을지대학교 대학원 2021 국내석사

Purpose: This study was conducted to evaluate the effect of aromatherapy using masks to treat allergy rhinitis symptoms, fatigue, and rhinitis-related quality of life. Methods: This study adopted an control group non-synchronized design. Eighty-five participants aged between 20 and 60 were randomized to the aroma group, placebo group, and control group. Aroma oil blending eucalyptus, lemon, Roman chamomile, and peppermint were provided to the aroma group, and jojoba oil was provided to the placebo group. Participants in the aroma and placebo groups applied a disposable face mask two times per day, for a 2-week duration. Participants in the control group received no treatment. Allergic rhinitis symptoms, as determined by Visual Analog Scale (VAS), Total Nasal Symptom Score (TNSS), and Allergic Rhinitis-Specific Quality of Life (ARSQOL), and fatigue level were measured before the intervention, and one week and two weeks after the intervention. Result: In the aroma group, allergic rhinitis symptoms showed significant improvement (VAS, TNSS). The aroma group also showed significantly higher improvements in ARSQOL. Conclusion: Aromatherapy dropped on masks help relieve allergic rhinitis symptoms, improve quality of life related to allergic rhinitis. So, it will be an effective nursing intervention that can be utilized in the easing of allergic symptom in COVID-19 era.

알레르기 비염 환자에서 기도 재형성과 YKL-40의 발현

이정열 순천향대학교 일반대학원 2008 국내석사

INTRODUCTION: YKL-40, a member of chitinase-like protein, has been known to be involved in the process of inflammation and tissue remodeling. Nasal airway remodeling appears in allergic rhinitis, but it appears to be far less extensive than in asthma. Although it has been known that the expression of YKL-40 was increased during Th2 type inflammation, its expression in allergic rhinitis has not been investigated. The aims of this study were to characterize nasal airway structural changes in allergic rhinitis and to examine the expression of YKL-40 in patients with allergic rhinitis and in healthy subjects. We also investigated whether the YKL-40 may take part in the process of airway remodeling in allergic rhinitis. METHODS: Nasal mucosa specimens were obtained from 20 patients with allergic rhinitis and 10 healthy subjects. Approval was obtained from the Human Research Ethics Board of the University of Soonchunhyang and informed consent obtained from all research subjects. Using histologic analysis, the following microscopic findings were compared between patients with allergic rhinitis and controls ; goblet cell hyperplasia, thickness of basement membrane, eosinophil infiltration, lymphocyte infiltration and macrophage infiltration, submucous gland formation. Immunohistochemical stain was performed for the detection of YKL-40. RESULTS: The number of eosinophils present within epithelial cells and in the submucosa (6.9±7.7 cells/HPF vs. 1.9±1.7 cells/HPF), and the number of total inflammatory cells(eosinophils+lymphocytes+macrophage) present within epithelial cells and in the submucosa(31.4 ± 25 cells/HPF vs 17.3±2.3 cells/HPF), and the thickness of basement membrane (11.6±2.7 μm vs. 2.5 ±1.5 μm) were significantly elevated in patients with allergic rhinitis as compared with controls (p<0.05). The numbers of goblet cells(2.3±0.7 grade vs. 2.2±0.9 grade), submucous gland formation(2.7±0.6 grade vs. 2.3±0.9 grade), lymphocytes(10.3±11.7 cells/HPF vs. 7.5± 4.3 cells/HPF)and macrophages(14.2±11.3 cells/HPF vs. 8.9±5.8 cells/HPF)present in the submucosa were not significantly different between patients with allergic rhinitis and controls (p>0.05). In the majority of patients with allergic rhinitis and controls, YKL-40 staining was seen in subepithelial cells near the basement membrane. Positive correlation was found between the number of YKL-40-positive cells and the thickness of basement membrane(r=0.52), the number of total inflammatory cells(r=0.45), the number of macrophage(r=0.41). CONCLUSIONS: we have shown that YKL-40 was found in increased quantities in patients with allergic rhinitis, in whom the expression of YKL-40 correlated positively with the thickness of the subepithelial basement membrane. Our data suggest that YKL-40 may participates in the process of airway remodeling of allergic rhinitis.

Decreased expression of E-cadherin and ZO-1 in the nasal mucosa of patients with allergic rhinitis : altered regulation of E-cadherin by IL-4, IL-5, and TNF-alpha

이현지 Korea University 2017 국내석사

Background : Allergic rhinitis is a chronic nasal inflammatory disease mediated by an IgE-mediated process to environmental allergens. Although atopy is a potent predisposing risk factor for allergic rhinitis, local tissue susceptibilities are inevitable for disease expression. The nasal epithelium maintains tissue homeostasis by providing a physical barrier controlled by epithelial junctional proteins. However, the expression of epithelial junctional proteins has not been studied in patients with allergic rhinitis. We sought to elucidate the expression and the regulation of epithelial junctional proteins in the nasal epithelium of patients with allergic rhinitis. Methods : The expression of E-cadherin and zonula occludens (ZO)-1 in epithelium of turbinate was measured using real-time PCR, Western blot, and immunohistochemical assays and compared between control subjects and patients with allergic rhinitis. In addition, the expression levels of E-cadherin and ZO-1 were determined in cultured epithelial cell treated with IL-4, IL-5, TNF-α, and IFN-γ. Results : The expression and the immunoreactivity of E-cadherin and ZO-1 were decreased in the nasal epithelium of patients with allergic rhinitis. Interestingly, the stimulation of cultured epithelial cells with IL-4, IL-5, and TNF-α resulted in downregulation of E-cadherin expression only in cultured epithelial cells of patients with allergic rhinitis, while E-cadherin expression in cultured epithelial cells of controls was not affected by stimulation with the same panel of cytokines. Conclusion : Decreased expression of epithelial junctional proteins was found in patients with allergic rhinitis. The disruption of epithelial integrity by IL-4, IL-5, and TNF-α in vitro indicates a possible role for these cytokines in the pathogenesis of patients with allergic rhinitis. 배경: 알레르기 비염은 알레르겐(알레르기 유발 항원)에 의한 면역글로불린 E 매개 만성적 코 염증 질환이다. 비록 아토피는 알레르기 비염의 유력한 소인성 위험 요소이지만, 질환 발병에 있어서 국부 조직 감염은 필연적이다. 코 상피는 상피 접합 단백질에 의해 조절되는 물리적 장벽을 형성하여 조직 항상성을 유지한다. 하지만, 아직까지 알레르기 비염 환자에서 상피 접합 단백질의 발현에 대한 연구가 부족하다. 따라서, 본 연구에서는 알레르기 비염 환자의 코 상피에서 상피 접합 단백질의 발현 양상과 조절 구조를 보고자 하였다. 방법: 비갑개의 상피에서 E-cadherin과 ZO-1의 발현은 실시간 중합효소연쇄반응, 단백질흡입법, 그리고 면역 조직화학적 분석을 이용하여 측정하였고 대조군과 알레르기 비염 환자를 비교하였다. 또한, 배양 상피세포에 IL-4, IL-5, TNF-α, 그리고 IFN-γ를 처리한 후 E-cadherin과 ZO-1의 발현 정도를 측정하였다. 결과: 알레르기 비염 환자의 코 상피에서 E-cadherin과 ZO-1의 발현과 면역반응성은 감소되어있었다. 흥미롭게도, 배양된 상피세포를 IL-4, IL-5, 그리고 TNF-α로 자극하였을 때 대조군에는 아무 영향이 없었던 반면, 오직 알레르기 비염 환자의 상피세포에서 E-cadherin의 발현이 감소되었다. 결론: 알레르기 비염 환자에서 상피 접합 단백질의 발현은 감소되어있었다. 생체외 실험에서 확인된 IL-4, IL-5, 그리고 TNF-α에 의한 상피의 붕괴는 알레르기 비염 환자의 병인에 있어 이러한 사이토카인들이 역할을 할 가능성을 나타낸다.

Urinary levels of phthalate metabolites and their association with allergic disorders in children and adolescents: Korean National Environmental Health Survey (KoNEHS) 2015-2017

이주연 Graduate School, Korea University 2021 국내석사

Phthalates are ubiquitous environmental chemicals that are used primarily in a vast array of consumer products. Exposures to these chemicals are frequent via various exposure routes, and children are more vulnerable to environmentally hazardous factors such as phthalates owing to the immaturity of their immune systems, compared to adults. Although increasing numbers of studies have reported that phthalate exposure could be a potential risk factor for allergic reactions, inconsistent associations between phthalate exposure and allergic disorders have been found across different populations. Therefore, we aimed to verify associations of urinary phthalate metabolite levels and self-reported current allergic symptoms and the indicator of allergic responses (the level of serum total immunoglobulin E, IgE) in a nationally representative sample of children and adolescents. In the present study, we recruited children and adolescents aged 3-17 years (n=2,208) from the Korean National Environmental Health Survey (KoNEHS) 2015-2017 to analyze their current allergic symptoms relating to atopic dermatitis, asthma, and allergic rhinitis. Among these participants, adolescents aged 12 years and older (n=806) were included in the analysis for total IgE levels because children aged 3-11 years had not undergone a total IgE examination. In addition, we stratified analyses by gender to evaluate any gender-based difference in associations with allergic symptoms and total IgE levels. The analysis for current allergic symptoms was also stratified based on age groups (infants, elementary school students, and middle and high school students). Furthermore, to assess the multimorbidity of allergic symptoms, allergic multimorbidity was defined as the co-existence of at least two current allergic symptoms (atopic dermatitis, asthma, or allergic rhinitis) in one individual. Odds ratio (OR) and their 95% confidence intervals (95% CI) per one ln-unit change in levels of phthalate metabolites were estimated using logistic regression analysis. After adjusting for potential confounders, mono-benzyl phthalate (MBzP) [OR (95% CI)=1.15 (1.01, 1.30)], mono-(carboxyoctyl) phthalate (MCOP) [OR (95% CI)=1.35 (1.02, 1.78)], the sum of di-(2-ethylhexyl) phthalate metabolites (∑DEHP) [OR (95% CI)=1.39 (1.09, 1.79)], mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) [OR (95% CI)=1.26 (1.01, 1.59)], and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) [OR (95% CI)=1.38 (1.14, 1.67)] showed positive associations with a risk of current atopic dermatitis. MCOP [OR (95% CI)=1.19 (1.01, 1.40)], mono-(carboxynonyl) phthalate (MCNP) [OR (95% CI)=1.24 (1.05, 1.45)], ∑DEHP [OR (95% CI)=1.22 (1.02, 1.44)], MEHHP [OR (95% CI)=1.21 (1.04, 1.41)], and MEOHP [OR (95% CI)=1.18 (1.04, 1.35)] were also significantly associated with a higher risk of current allergic rhinitis. When further stratified by gender and age groups, associations with allergic disorders differed in different gender and age groups. In particular, MCOP [OR (95% CI)=2.07 (1.10, 3.87)] and mono-n-butyl phthalate (MnBP) [OR (95% CI)=1.75 (1.02, 3.00)] were significantly associated with a higher risk of current asthma in male and female participants, respectively and MCNP [OR (95% CI)=4.73 (1.46, 15.33)] and MnBP [OR (95% CI)=3.45 (1.26, 9.43)] showed the positive association with the odds of current asthma in infants and middle and high school students, respectively, while no phthalate metabolites were significantly associated with current asthma in the overall population. In addition. the OR for high total IgE levels (>100 IU/mL) increased as the concentrations of urinary MCNP elevated [OR (95% CI)=1.43 (1.06, 1.91)]. MBzP [OR (95% CI)=1.17 (1.01, 1.35)], MCOP [OR (95% CI)=1.62 (1.12, 2.32)], and MEOHP [OR (95% CI)=1.36 (1.06, 1.76)] were also positively associated with allergic multimorbidity. Furthermore, elevated concentrations of MCNP were more likely to increase the odds of both experiencing current allergic symptoms (asrhma or allergic rhinitis) and having high total IgE levels (asthma: p=0.052; allergic rhinitis: p=0.007). The positive association between MCNP and current allergic rhinitis was partly driven by changes in IgE levels (14.7%), and the increase in urinary MCNP concentrations also directly affected the development of allergic rhinitis symptoms, independent of IgE (85.3%). Overall, higher levels of several phthalate metabolites in urine were significantly associated with an increased risk of allergic disorders. The present observations suggest that environmental exposure to phthalates may exacerbate allergic responses and contribute to an increased risk of the development of allergic disorders in children and adolescents. 프탈레이트는 우리 생활에 필요한 여러 소비자 제품에 가소제로 사용되는 산업 화학물질이다. 인간은 다양한 경로를 통해 프탈레이트에 빈번하게 노출되며, 특히 어린이는 성인에 비해 면역체계가 미성숙하므로 프탈레이트 노출에 더 취약하다. 일부 선행 연구들을 통해 프탈레이트 노출은 아동의 알레르기 반응에 대한 잠재적인 위험 인자가 될 수 있다고 밝혀진 바 있으나, 프탈레이트 노출과 알레르기 질환 사이의 연관성은 다양한 모집단을 활용한 연구에서 일관되지 않는 경향을 보였다. 따라서 본 연구에서는, 한국 어린이와 청소년을 대표하는 인구 집단을 활용하여 요중 프탈레이트 대사체의 농도와 자가 보고된 현재 알레르기 증상 및 알레르기 반응의 지표인 총 면역글로불린 E (IgE) 간의 연관성을 검증해보고자 하였다. 본 연구는 어린이와 청소년의 현재 알레르기 증상 분석을 위해 국민환경보건기초조사 (KoNEHS) 2015-2017 자료를 이용하였고 연구 대상을 3-17세 어린이 및 청소년 (n=2,208)으로 한정시켰다. 전체 참가자 중, 3-11세 어린이의 경우 총 IgE 수치가 측정되지 않았기 때문에 혈중 총 IgE 농도를 측정한 806명의 청소년 (12-17세의 중고등학생)이 총 IgE 농도 분석에 포함되었다. 또한, 모든 분석을 성별로 층화하여 각 성별에서 나타나는 연관성의 차이를 확인하였고 현재 알레르기 질환 분석의 경우 추가적으로 연령대로 층화하여 각 연령대 (영유아, 초등학생, 중고등학생)에서 나타나는 연관성의 차이를 확인하였다. 또한 한 개인에서 최소 두 개의 알레르기 증상이 공존하는 알레르기 다중 이환 현상을 확인하기 위해 로지스틱 회귀분석을 이용하여 오즈비와 95% 신뢰구간을 산출하였다. 모든 공변량을 보정한 후, Mono-benzyl phthalate (MBzP), mono-(carboxyoctyl) phthalate (MCOP), di-(2-ethylhexyl) phthalate의 대사체들의 농도 합 (∑DEHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) 및 mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP)와 현재 아토피 피부염 증상 간의 양의 연관성이 관찰되었으며, MCOP, mono-(carboxynonyl) phthalate (MCNP), ∑DEHP, MEHHP 및 MEOHP는 현재 알레르기 비염 증상과 양의 연관성을 나타내었다. 또한, 세 가지 질환 모두 성별과 연령대에 따라 프탈레이트 대사체 농도와의 연관성의 차이를 보였다. 특히, 전체 인구 집단에서 프탈레이트 노출과 현재 천식 증상 간의 유의한 연관성이 관찰되지 않았지만, MCOP는 남성에서, mono-n-butyl phthalate는 여성과 중고등학생에서, MCNP는 영유아에서 현재 천식 증상 발현과 양의 상관성을 나타내었다. MCNP의 농도가 높아짐에 따라 높은 총 IgE 농도 (>100 IU/mL)를 가질 확률이 증가했으며, MBzP, MCOP 및 MEOHP는 알레르기 다중 이환과 연관이 있는 것으로 나타났다. 또한, 높은 MCNP 농도는 알레르기 증상과 높은 IgE 농도를 동시에 경험할 확률을 증가시켰다. 특히, MCNP와 현재 알레르기 비염 간의 양의 연관성은 IgE 농도의 변화에 의해 일부 매개되었고 (14.7%), MCNP 농도의 증가는 IgE와 독립적으로 알레르기 비염 증상 발현에 직접적인 영향 (85.3%)을 미쳤다. 본 연구의 결과를 통해 높은 프탈레이트 대사체 농도는 자가보고된 현재 알레르기 증상과 알레르기 반응의 지표인 높은 총 IgE 농도와 유의한 연관성을 보였다. 즉, 환경 중 프탈레이트에 노출될수록 알레르기 장애의 위험이 증가함을 관찰하였다. 이러한 결과는 환경 중 프탈레이트 노출이 알레르기 반응을 악화시킬 수 있으며 어린이와 청소년에서 알레르기 질환의 발병 위험을 증가시킬 수 있음을 시사한다.

프로바이오틱스의 알러지성 비염 개선 효과

김원경 경희대학교 대학원 2018 국내석사

The purpose of this study was to examine how the administration of probiotics on ovalbumin-induced allergic rhinitis mice inhibits the allergic response. First, we isolated three types of Bifidobacterium longum(BL1, BL2, BL3) from human fecal microbiota and three types of Lactobacillus plantarum(LP1, LP2, LP3) from kimchi. We selected BL2 and LP2 which increased IL-10 expression in LPS - stimulated dendritic cells. Two different strains, BL2 and LP2, were treated with Th2 cell and Treg cell differentiation factors in T0 cells. We confirmed that BL2 and LP2 inhibited Th2 cell differentiation and promoted Treg cell differentiation. To determine whether IL-10 expression-inducing probiotics could regulate allergic rhinitis in vivo, a solution containing OVA and aluminum was intraperitoneally administered twice to induce an allergic reaction to OVA, and a 1% OVA solution was administered to the nose to induce allergic rhinitis mouce models. In order to confirm the alleviation effect of probiotics, BL2, LP2 and its mixture were administered orally, and dexamethasone was administered intraperitoneally as a positive control. To investigate the effects of probiotics on allergic rhinitis, rubbing motion was measured and histopathologic examination of the nasal cavity and lung and inflammatory measurements in the nasal mucosa, bronchial, blood, and lungs were performed. Oral administration of BL2, LP2 or their mixture significantly reduced OVA-induced allergic nasal symptom and blood IgE levels in mice. These also suppressed OVA-induced IL-4 and IL-5 in nasal tissues and populations of mast cells, eosinophils, and Th2 cells and increased OVA-suppressed population of Treg cells in bronchoalveolar lavage fluid (BALF). Treatment with BL2, LP2 or MIX reduced OVA-induced IL-4 and IL-5 levels in the BALF and blood but increased OVA-suppressed IL-10 levels. Treatment with BL2, LP2 or MIX significantly inhibited OVA-induced disruption and dilation of epithelial cells in the lung and expression of GATA3 and IL-5 and increased Foxp3 and IL-10 expression. In addition, BL2, LP2 or MIX significantly inhibited the OVA-induced population of Proteobacteria, and increased the OVA-suppressed populations of Bacteroidetes and Actinobacteria. These results suggest that BL2 and LP2 can alleviate allergic rhinitis by inhibiting IL-5 expression and Th2 differentiation, inducing IL-10 and Treg cells. In addition, the administration of BL2 and LP2 were effectively controlling the activity of allergen-mediated cells and the symptoms of allergic rhinitis. Futhermore BL2 and LP2 showd the effect of improving immunity by restoring gut microbiota composition. BL2 and LP2 had similar antiallergic effect. Mixture of BL2 and LP2 had only an additive effect, but all probiotics showed anti - allergic effect of dexamethasone. As a result, the functional probiotics BL2 and LP2, isolated from human fecal microbiota and kimchi, are expected to effectively alleviate allergic rhinitis and inhibit Th2 cells mediated allergic diseases as well as allergic rhinitis. In addition, the intake of functional probiotics suggests that the balance of intestinal microbiota can be controlled to promote and strengthen the overall immunity of the human body, thereby helping to prevent and treat the disease.

알레르기성 비염의 변증과 평가방법에 대한 고찰

김지은 대구한의대학교 대학원 2016 국내석사

Objective : An adequate measurement for allergic rhinitis is essential for studies about the treatment of allergic rhinitis. To establish a new and adequate scoring system for allergic rhinitis in Korean medicine, we reviewed existing studies on allergic rhinitis outcome measurement in Korean medicine. Method : We searched for reviews on measurements of allergic rhinitis or studies which used an allergic rhinitis outcome measurement at the Korea Traditional Knowledge Portal from 2000 to 2015. And then we reviewed the pattern identification in allergic rhinitis patients and the outcome measurements for allergic rhinitis in each study. Results : Among 27 studies, there were 24 studies which used subjective symptoms of allergic rhinitis, 9 studies which used quality of life. In Korean medicine, Most of Allergic rhinitis were caused by Spleen-Gi deficiency. Conclusion : We need to establish a new severity scoring system which reflects pattern identifications and treatments with Korean medicine, and we should assess the validity, reliability, and sensitivity of the new scoring system. 목적 : 알레르기성 비염에 대한 치료효과를 평가하고 임상시험을 통한 근거를 마련하기 위해서는 임상적인 관찰을 통한 적절한 평가방법을 마련하는 것이 필수적이다. 이에 본 연구에서는 향후 알레르기성 비염의 진단 및 평가를 위해서 사용할 수 있는 평가척도를 마련하기위해 알레르기성 비염에 관한 한방연구에서는 어떤 평가척도들이 사용되고 있는지 또는 어떤 평가척도를 제시했는지를 살펴보았다. 연구방법 : 한방치료에서 사용되고 있는 알레르기성 비염의 평가방법을 정리하기 위해 2000년부터 2015년까지 알레르기성 비염과 관련된 논문을 검색하였다. 알레르기성 비염에 대한 임상논문을 위주로 사용하고 있는 평가방법에 대해서 살펴보았다. 결과 : 27편의 연구 중 鼻 증상 평가 및 鼻 외 증상을 포함한 전반적인 알레르기 비염 관련 증상 평가는 24편, 삶의 질 평가는 9편에서 사용되었다. 한의학에서 알레르기 비염 대부분은 脾氣虛로 인한 것이었다. 결론 : 알레르기성 비염에 대해 변증과 연관 지을 수 있는 항목을 연구하여 한의학적 관점에 의한 치료를 반영하는 새로운 평가방법의 개발이 필요하며 각 항목에 대한 구체적인 지침을 통해 재현성을 확보해야 한다. 또한 이에 대한 타당성과 신뢰성, 민감성 연구를 통한 검증이 이루어 져야 한다.

Protective effects of the extract of Lithospermum erythrorhizon and active compounds on allergic and inflammatory diseases

강태겸 강릉원주대학교 일반대학원 2024 국내박사

General Abstract. This dissertation investigates the protective effects of the extract of Lithospermum erythrorhizon (LE) and its active compounds on allergic and inflammatory diseases, focusing on allergic rhinitis and uveitis. LE is a medicinal plant that has been used in traditional medicine for various purposes, such as anti-inflammatory, antipyretic, and anti-allergic. The dissertation aims to identify the various active components of LE that mediate its activities and is divided into two chapters. Each chapter explores the protective effects of LE and active compounds in models of allergic and inflammatory diseases. Chapter 1 examines the antiallergic effects of LE and N,N`-dicoumaroylspermidine, a novel compound isolated from LE, on mast cells and ovalbumin (OVA)-induced allergic rhinitis in mice. The chapter demonstrates that LE and N,N`-dicoumaroylspermidine can effectively suppress the allergic response by inhibiting mast cell degranulation, reducing the production of Th2 cytokines and OVA-specific immunoglobulins, and alleviating nasal symptoms and inflammation. Chapter 2 investigates the anti-inflammatory effects of LE and three of its compounds, shikonin, acetylshikonin, and β, β-dimethylacryloylshikonin, on endotoxin-induced uveitis (EIU) in rats and mice. The chapter shows that LE and its compounds can significantly reduce the severity of uveitis by decreasing the clinical inflammatory score, retinal thickness, protein concentration, prostaglandin E2 levels, and cellular infiltration in the aqueous humor. The chapter also reveals that LE and its compounds can inhibit the expression of pro-inflammatory cytokines and the activation of NF-κB/AP-1 and IRF signaling pathways in vitro and in vivo. The dissertation concludes that LE and its active compounds have potent protective effects on inflammatory and allergic diseases, especially allergic rhinitis and uveitis, and suggests that they could be potential candidates for developing new plant-based therapies for these conditions. The dissertation also provides novel insights into the chemical diversity and pharmacological mechanisms of LE and its constituents. Chapter1 Abstract. In East Asia, the dried root of LE has a long history of use as an anti-inflammatory, antipyretic, detoxifying, and anti-allergic agent. Building on our previous findings that LE offers protective effects against allergic rhinitis, this study delves deeper to identify and characterize the specific antiallergic active components within an ethanolic extract of LE roots. To achieve this, we employed an ovalbumin (OVA)-induced allergic rhinitis mouse model to evaluate the antiallergic effects of LE reflux ethanol extracts. A comparative analysis was conducted between the chemical compounds extracted using both hot reflux and cold extraction methods to ascertain the most effective extraction technique. Through chromatographic separation, our research successfully identified two novel anthraquinones, named erythrin A and B, and a newly discovered compound unique to the Lithospermum genus, N,N`-dicoumaroylspermidine, along with nineteen other recognized compounds. The structural elucidation of these compounds was achieved through comprehensive single (1D) and 2D nuclear magnetic resonance (NMR) spectroscopic data analysis, supported by high-resolution mass spectrometry. Of the compounds identified, N,N`-dicoumaroylspermidine emerged as a standout, demonstrating a strong inhibition of β-hexosaminidase release, and significantly reducing the production of interleukins IL-3, IL-4, and IL-13 in IgE-sensitized and BSA-stimulated RBL-2H3 cells. Furthermore, using the OVA-induced allergic rhinitis mouse model, N,N-dicoumaroylspermidine showed a notable reduction in serum OVA-specific IgE levels and a decrease in the number of inflammatory cells in nasal lavage fluid. These findings underscore the potential of N,N-dicoumaroylspermidine, isolated from LE, as an effective antiallergic agent, particularly for the management of allergic rhinitis. This study not only sheds light on the antiallergic properties of LE but also opens avenues for further research into its therapeutic applications in allergic conditions. Chapter2 Abstrat. Uveitis is an inflammatory eye condition that threatens vision, and effective anti-inflammatory treatments with minimal side effects are necessary to treat uveitis. This study aimed to investigate the effects of LE against endotoxin-induced uveitis in rat and mouse models. Endotoxin-induced uveitis models of rats and mice were used to evaluate the effects of LE treatment. Clinical inflammation scores and retinal thickness were assessed in the extract of LE rats. Histopathological examination revealed inflammatory cell infiltration into the ciliary body. Protein concentration, cellular infiltration, and prostaglandin-E2 levels were measured in the aqueous humor of the extract of LE-treated rats. Protective effects of LE on the anterior segment of the eye were examined in mice with endotoxin-induced uveitis. Additionally, we investigated the effect of LE the expression of pro-inflammatory cytokines in lipopolysaccharide-stimulated THP1 human macrophages and examined the involvement of nuclear factor kappaB (NF-κB)/activator protein 1 and interferon regulatory factor signaling pathways. Furthermore, three components of LE were identified and assessed for their inhibitory effects on LPS-induced inflammation in RAW264.7 macrophage cells. Treatment of the extract of LE significantly reduced clinical inflammation scores and retinal thickening in rats with endotoxin-induced uveitis. Histopathological examination revealed decreased inflammatory cell infiltration into the ciliary body. The extract of LE effectively reduced the protein concentration, cellular infiltration, and PG-E2 levels in the aqueous humor of rats with endotoxin-induced uveitis. In mice with endotoxin-induced uveitis, the extract of LE demonstrated a protective effect on the anterior segment of the eye by reducing inflammation and retinal thickening. The extract of LE suppressed the expression of pro-inflammatory cytokines in lipopolysaccharide-induced inflammation in THP1 human macrophages, by modulating NF-κB/activator protein 1 and interferon regulatory factor signaling pathways. Moreover, shikonin, acetylshikonin, and β, β-dimethylacryloylshikonin showed dose-dependent inhibition of nitric oxide, NF-κB and interleukin-6 production in RAW264.7 macrophage cells. The extract of LE is a potential therapeutic agent for uveitis management. Administration of the extract of LE led to reduced inflammation, retinal thickening, and inflammatory cell infiltration in rat and mouse models of uveitis.

알레르기 비염의 비점막에서 leptin수용체의 발현

주은정 고려대학교 대학원 2009 국내박사

=Abstract= Expression of leptin receptor in nasal mucosa of allergic rhinitis Eun-jeong Joo, MD Department of Medical Science, Graduate School, Korea University (Director: Prof. Seung Hoon Lee, MD., Ph.D.) Objectives: Allergic rhinitis is symptomatic disorder of a nose induced by IgE-mediated inflammation. Various inflammatory mediators have been identified in the pathogenesis of allergic rhinitis. Leptin plays an important role in energy homeostasis and controlling body weight. Recent studies showed that serum leptin level was increased in allergic rhinitis, when compared with normal control. The purpose of this study was to investigate the expression of leptin receptor in the allergic nasal mucosa in compared with that in normal healthy control. Material and Methods: Inferior turbinate mucosa of 10 allergic rhinitis and 10 healthy controls were collected. Semi quantitative reverse transcription-polymerase chain reaction for leptin receptor mRNA was performed, and leptin receptor protein was detected western blotting analysis and localized by using immunohistochemical staining Results: The expression level of leptin receptor mRNA and protein were significantly increased in allergic nasal mucosa compared with those in normal healthy control. Leptin receptor protein was strongly expressed in the epithelial cells and infiltrating inflammatory cells of allergic nasal mucosa. Conclusions: Leptin receptor is expressed in nasal mucosa of healthy control and allergic rhinitis, and its expression is increased in allergic rhinitis. These results suggest that the increased expression of leptin receptor in allergic nasal mucosa may play an important role in the pathogenesis of allergic rhinitis. Key Words: Leptin, Leptin receptor, Allergic rhinitis

알레르기비염에서 acidic mammalian chitinase의 발현

최현진 고려대학교 대학원 2010 국내석사

Background : Acidic acidic mammalian chitinase (AMCase) may be needed for the increased production of the chemoattractants of many inflammatory cells. Increased production of these chemoattractants could result in the increase in inflammatory infiltrates observed in allergic rhinitis. Objectives: The purposes of this study were to investigate the expression of AMCase mRNA, to localize the expression of AMCase protein in allergic rhinitis and, and to measure AMCase activity in normal and allergic rhinitis nasal mucosa. Materials and Methods: Inferior turbinate mucosa samples and nasal secretions from 20 patients with perennial allergic rhinitis and 20 matched normal control subjects were obtained. AMCase mRNA was extracted from the inferior turbinate mucosa, then reverse transcriptase-polymerase chain reaction was performed and analyzed semiquantitatively. AMCase protein was localized immunohistochemically and AMCase activity was measured in nasal secretions. Results: The expression levels of AMCase mRNA were significantly increased in patients with allergic rhinitis mucosa. AMCase protein was predominantly localized in the surface epithelium, infiltrating inflammatory cells, and submucosal glands and was more strongly expressed in the nasal mucosa of patients with allergic rhinitis than in normal control subjects. AMCase activity level was higher in allergic rhinitis mucosa than in normal control. Conclusions: AMCase may be a mediator in the pathogenesis of allergic rhinitis, suggesting a potential therapeutic target in these allergic rhinitis.

알레르기 비염에서 Interleukin-18/ -607 유전자 다형성

박숙아 고려대학교 대학원 2005 국내석사

Background and Objectives: Allergic rhinitis is a chronic inflammatory disease with a genetic background. IL-18, formerly called the IFN--inducing factor, is a pro-inflammatory cytokine. The aim of this study was to investigate the association between IL-18 polymorphism with allergic rhinitis and its phenotypein Korean population. Materials and Methods: DNAswere obtained from 160 Korean patients with allergic rhinitis, and 166 healthy controls. IL-18/-607 polymorphism were analyzed by polymerase chain reaction with restriction fragment length polymorphisms (PCR-RFLP)in both groups, followed by analysis of the association between polymorphism and allergic rhinitis. Results: The frequency of AC genotype of IL-18/-607 gene polymorphism was significantly higher in allergic rhinitis patients than in controls. In case of allergic rhinitis, total IgE levels are significantly elevated in AA homozygote than in CC homozygote and AC heterozygote. AA homozygote showed increased rate of positive skin test compared with CC and AC alleles. Conclusions: Il-18 gene polymnorphism is strongly associated with allergic rhinitis.