Suppressive effects of fermented Platycodon grandiflorum extract on airway inflammation and Aster glehni extract on hyperuricemia
- 주제(키워드) hyperuricemia , extract , airway inflammation
- 발행기관 고려대학교 대학원
- 지도교수 강성만
- 발행년도 2021
- 학위수여년월 2021. 2
- 학위구분 박사
- 학과 대학원 생명과학과
- 세부전공 분자생물학
- 원문페이지 100 p
- UCI I804:11009-000000235577
- DOI 10.23186/korea.000000235577.11009.0001163
- 본문언어 영어
초록/요약
Platycodon grandiflorum (PG) has been extensively utilized as an herb to relieve phlegm. In this study, the effects of P. gandiflorum root extracts on airway inflammation and cough reflex were investigated, especially using fermented PG extracts (FPE) to increase an active compound, platycodin D by fermentation. FPE significantly reduced the numbers of eosinophils and total cells in the bronchoalveolar lavage fluid (BALF) obtained from lipopolysaccharide/ovalbumin-induced asthma mice versus those of vehicle control. Moreover, in the BALF and the serum, FPE significantly reduced the concentration of IL-17E, a pro-inflammatory cytokine that causes TH2 immunity including eosinophil amplification. It was also demonstrated that FPE might relieve inflammations through histological analysis of the lung separated from each mouse. Furthermore, in cough reflex guinea pigs induced by citric acid treatment, FPE treatment significantly reduced the number of coughs versus that of vehicle control, and consequently decreased cough reflex sensitivity. In addition, the total cell number and eosinophils significantly decreased in the BALF obtained from each guinea pig versus that of vehicle control. In in vitro study, pretreatment with FPE in LPS-stimulated RAW264.7 cells significantly reduced the levels of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1β, and inducible nitric oxide synthases (iNOS). Therefore, we demonstrated that FPE relieved airway inflammation and cough reflex sensitivity in vivo, and exhibited anti-inflammatory effects via suppression of iNOS and several pro-inflammatory cytokines. These findings suggest that FPE might have a beneficial effect on respiratory health, and may be useful as a functional food to prevent respiratory diseases.
more초록/요약
Aster glehni is a perennial plant exclusively growing in Ulleung Island, South Korea. In this study, molecular mechanisms of Aster glehni extracts (AGE) to reduce serum uric acid levels were investigated using potassium oxonate (PO)-induced hyperuricemia rats. AGE-treated groups significantly lowered uric acid levels in the blood compared to the PO control group. Treatments with 300 or 500 mg/kg of AGE, but not 100 mg/kg, significantly inhibited hepatic xanthine oxidase (XOD) activity related to uric acid production, compared to the PO control group. Furthermore, AGE treatment reduced the protein levels of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1) in renal tissues of rats, indicating a decrease of urate reabsorption into circulation. From the result of measuring blood creatinine, urea nitrogen, aspartate transaminase, and alanine transaminase, it was demonstrated that AGE did not negatively affect the renal function, and had preventive effects on PO-induced hepatic damages, unlikely drugs for treating hyperuricemia. Therefore, our findings suggest that AGE may have effects on lowering the level of serum uric acid due to both a reduced uric acid production by suppressing XOD activity in the liver, and a reduced urate reuptake by regulating the protein level of URAT1 and GLUT9 in the kidney.
more목차
CONTENTS i
LIST OF FIGURES iii
LIST OF ABBREVIATIONS v
BACKGROUND 1
1. Fermented Platycodon grandiflorum (FPG) 2
1.1. Platycodon grandiflorum (PG) 2
1.2. Active ingredients of PG 2
1.3. Allergic asthma and animal model 3
1.4. Fermentation of PG 6
2. Ethanol extracts of Aster glehni (AGE) 10
2.1. Aster glehni 10
2.2. Hyperuricemia 10
2.3. Xanthine oxidase (XOD) 11
2.4. Renal uric acid excretion 13
2.5. Material standardization 13
3. General development process of functional foods 17
4. References 21
CHAPTER I. Fermented Platycodon grandiflorum extracts relieve airway inflammation and cough reflex sensitivity in vivo 26
CHAPTER Ⅱ. Effects of Aster glehni extract on serum uric acid in subjects with mild hyperuricemia: a randomized, placebo-controlled trial 39
CHAPTER Ⅲ. Molecular mechanisms of Aster glehni extracts on lowering serum uric acid levels in potassium oxonate-induced hyperuricemic rats (Unpublished data) 51
1. Abstract 52
2. Introduction 53
3. Material & methods 55
4. Results 61
4.1. AGE reduced uric acid levels in the blood in PO-induced hyperuricemia rats 61
4.2. AGE had an inhibitory effect on hepatic XOD activity in PO-induced hyperuricemia rats 63
4.3. AGE reduced GLUT9 and URAT1 protein levels in renal tissues of PO-induced hyperuricemia rats 65
4.4. AGE did not affect the renal function negatively and had a preventive effect from hepatic injury induced by PO administration 68
5. Discussion 71
6. References 75
FINAL CONCLUSIONS vi
ABSTRACT IN KOREAN xi
ACKNOWLEDGEMENTS xvii
