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제주 식물자원을 이용한 천식의약품 활성소재 연구

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Alternative Title
Study of Medicinal Activation Materials for Asthma from the Natural Plants in Jeju Island
Abstract
The purpose of this study is to discover natural products for the anti-asthmatic activity using the solvent-extracts derived from native 100 plants in Jeju area. The extracts were tested for the ability to inhibit Phosphodiesterase4(PDE4) (Target 1) and GSNO reductase (Target 2), which are recently considered as therapeutic targets for asthma. The hits that showed excellent efficacy against two targets were further characterized by separation of leaves and branches, extraction and solvent (n-hexane, ethyl acetate, and n-butanol) fractionation, and then testing the activity of each extract against the targets in vitro. These efforts led to the identification of C. macrophylla, D. racemosum, and P. villosa. The efficacy of three natural products was further evaluated in a mouse model of allergic asthma, and chemical ingredients of each plant were analyzed using UHPLC-HR MS/MS and LCQ Fleet Ion Trap MS. In a mouse model of allergic asthma, D. racemosum extract was best among the natural products with regards to the anti-inflammatory activity; administration of D. racemosum to a mouse model of allergic asthma significantly reduced inflammatory response in the lung, as well as serum immunoglobulin E levels. In addition, D. racemosum exhibited no detectable toxicity in rats; at a dose of 2,000 mg/kg, D. racemosum did not cause any changes in body weight and organs in male and female animals. UHPLC-HR MS/MS and a dereplication method were applied to analyze the compound ingredients in three excellent resources, and as a results, 13 and 5 types of compounds were identified in D. racemosum and P. villosa, respectively. Eleven compounds among identified compounds were purchased and the qualitative confirmation test was carried out using LCQ Fleet Ion Trap MS for three natural products (C. macrophylla, D. racemosum, and P. villosa). The analyses identified 8 compounds in C. macrohylla and 11 compounds in P. villosa. In addition, 14 compounds were identified in D. racemosum which showed the best anti-inflammatory effects in an animal model of asthma. It is of interesting that catechin, hyproside, rutin, quercitrin, and quercetin were indcluded in all three plant extracts. In conclusion, our results suggest that the extract of D. racemosum exhibits an excellent anti-asthmatic effect, and provide sufficient basis for the extract of D. racemosum to be used as an asthma medicine, although mechanism of action and the active ingredients need to be further investigated.
Author(s)
한종헌
Issued Date
2019
Awarded Date
2019. 2
Type
Dissertation
URI
http://dcoll.jejunu.ac.kr/common/orgView/000000008936
Alternative Author(s)
Han, Jong Heon
Affiliation
제주대학교 대학원
Department
대학원 화학과
Advisor
강창희
Table Of Contents
LIST OF CONTENTS iv
LIST OF TABLES vii
LIST OF FIGURE iv
LIST OF SCHEMES xiii
ABSTRACT xiv
I. 서 론 1
II. 실험방법 10
1. 시약 및 기기 10
1-1. 시약 10
1-2. 기기 12
2. 시험방법 13
III. 결과 및 고찰 31
1. 식물자원 탐색 및 선정 31
1-1. 제주 식물자원 탐색 23
1-2. 천식 억제 효능 탐색 및 식물자원 선정 39
2. 곰의말채나무 천식효능 탐색 48
2-1. 곰의말채나무 특성 48
2-2. 곰의말채나무 잎 추출 50
2-3. 곰의말채나무 잎 추출 성분 활성 확인 51
2-4. 곰의말채나무 가지 추출 54
2-5. 곰의말채나무 가치 추출 성분 활성 확인 55
2-6. 곰의말채나무 추출 성분 구조 분석 58
2-6-1. 표준물질 분석 58
2-6-2. 추출 성분 분석 58
2-7. 곰의말채나무 추출 성분 동물 실험 106
2-7-1. 기도과민성에 미치는 영향 106
2-7-2. 활성산소족 억제 효과 108
2-7-3. 폐포 세척액 내 염증세포 침윤 억제 효과 109
2-7-4. 염증성 Cytokine 생성 억제 효과 111
2-7-5. Immunoglobulin-E 생성 억제 효과 114
2-7-6. 폐조직 내 염증세포 침윤 억제 효과 115
2-7-7. 점액분비 억제 효과 118
3. 조록나무 천식효능 탐색 121
3-1. 조록나무 특성 121
3-2. 조록나무 잎 추출 123
3-3. 조록나무 잎 추출 성분 활성 확인 124
3-4. 조록나무 가지 추출 127
3-5. 조록나무 가지 추출 성분 활성 확인 128
3-6. 조록나무 추출 성분 구조 분석 131
3-6-1. 화합물 구조 동정 131
3-6-2. 추출 성분 분석 136
3-7. 조록나무 추출 성분 동물 실험 150
3-7-1. 기도과민성에 미치는 영향 150
3-7-2. 활성산소족 억제 효과 152
3-7-3. 폐포 세척액 내 염증세포 침윤 억제 효과 153
3-7-4. 염증성 Cytokine 생성 억제 효과 155
3-7-5. Immunoglobulin-E 생성 억제 효과 158
3-7-6. 폐조직 내 염증세포 침윤 억제 효과 160
3-7-7. 점액분비 억제 효과 163
4. 윤노리나무 천식효능 탐색 166
4-1. 윤노리나무 특성 166
4-2. 윤노리나무 잎 추출 168
4-3. 윤노리나무 잎 추출 성분 활성 확인 169
4-4. 윤노리나무 가지 추출 172
4-5. 윤노리나무 가지 추출 성분 활성 확인 173
4-6. 윤노리나무 추출 성분 구조 분석 176
4-6-1. 화합물 구조 동정 176
4-6-2. 추출 성분 분석 179
4-8. 윤노리나무 추출 성분 동물 실험 190
4-8-1. 기도과민성에 미치는 영향 190
4-8-2. 활성산소족 억제 효과 192
4-8-3. 폐포 세척액 내 염증세포 침윤 억제 효과 193
4-8-4. 염증성 Cytokine 생성 억제 효과 195
4-8-5. Immunoglobulin-E 생성 억제 효과 198
4-8-6. 폐조직 내 염증세포 침윤 억제 효과 200
4-8-7. 점액분비 억제 효과 203
5. 조록나무 추출물 독성 연구 206
5-1. 사망유무 206
5-2. 일반증상 207
5-3. 체중변화 209
5-4. 육안적 부검소견 211
IV. 요약 및 결론 213
V. 참 고 문 헌 215
Degree
Doctor
Publisher
제주대학교 대학원
Citation
한종헌. (2019). 제주 식물자원을 이용한 천식의약품 활성소재 연구
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General Graduate School > Chemistry
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