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Investigation of the anti-osteoporotic activity of Edgeworthia papyrifera and Edgeworoside A and anti-melanogenic activity of Rhizoma arisaematis
삼지닥과 Edgeworoside A의 항골다공증 및 천남성의 미백 효과에 관한 연구

DC Field Value Language
dc.contributor.advisor서진호-
dc.contributor.author김판수-
dc.date.accessioned2018-05-28T16:34:09Z-
dc.date.available2020-05-06T02:23:19Z-
dc.date.issued2018-02-
dc.identifier.other000000150715-
dc.identifier.urihttps://hdl.handle.net/10371/140791-
dc.description학위논문 (박사)-- 서울대학교 대학원 : 농업생명과학대학 농생명공학부, 2018. 2. 서진호.-
dc.description.abstractNatural products have been considered a rich source of new drugs, nutraceuticals and cosmeceuticals for decades. Efforts on discovering new bioactive ingredients with drug-like benefits from natural products have been aided greatly by the availability of natural product-derived libraries (collection of crude mixtures, fractions, and purified compounds). In this thesis, a library of extracts derived from 4,200 plants native to Korea was exploited to identify candidates for anti-osteoporosis agents and anti-melanogenic agents.
The approach to discover candidates for anti-osteoporosis agents involves a series of assays that utilize biomarkers for osteoclast and osteoblast differentiation: the library was screened for the ability to inhibit RANKL-induced NF-κB (nuclear factor–kappa B) expression in RAW 264.7 osteoclatic cells, to modulate the activity of alkaline phosphatase in MC3T3-E1 osteoblastic cells, and to enhance the deposition of extracellular calcium in osteoblasts in vitro. These efforts in conjunction with a dereplcation technology led to identification of Edgeworthia papyrifera and edgeworoside A which exhibited a desired bioactivity profile in vitro. In an animal model of post-menopousal osteoporosis, E. papyrifera was demonstrated to improve all of the osteoporosis relevant parameters, suggesting that E. papyrifera and edgeworoside A may be used as functional ingredients in health supplements to increase bone strength and as therapeutics to treat osteoporosis.
Identification of candidates for anti-melanogenic agents involves a series of tests that utilize α-MSH-stimulated melanogenesis in vitro and quantification of tyrosinase and TRP1 expression in B16F1 cells. The efforts led to identification of Rhizoma arisaematis that inhibited biosynthesis of melanin and expression of tyrosinase and TRP1 in α-MSH-treated B16F1 cells. The anti-melanogenic effect of R. arisaematis was mediated through activation of autophagy in B16F1 cells, and pharmacological inhibition of autophagy reduced the anti-melanogenic activity of R. arisaematis in α-MSH-treated B16F1 cells. Further analyses of R. arisaematis using three-dimensional skin substitutes and in a human clinical trial revealed that it significantly suppressed pigmentation and exerted whitening effects on human skin. These observations serve as a basis for further elaboration of R. arisaematis for the development of functional skin care products.
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dc.description.tableofcontentsChapter 1. Literature review 1
1.1. Overview of natural products from plants 2
1.1.1. Natural products from plants 2
1.1.2. Natural products as drug and ingredients for health food and cosmetic 5
1.2 Osteoporosis and plant natural products 9
1.2.1. The nature of osteoporosis 9
1.2.2. Drugs and osteoporosis 14
1.2.3. Mechanism of Osteoporosis 24
1.2.4. Natural products for treatment of osteoporosis 35
1.3. Natural products from plants for whitening 66
1.3.1. Plant natural products for cosmetic ingredients 66
1.3.2. Melanogenesis and whitening 69
1.3.3. Autophagy and whitening 76
1.4. Objectives of the dissertation 82
Chapter2. Effects of Edgeworthia papyrifera and Edgeworoside A on osteoporosis as potent preventive and therapeutic agents 83
2.1. Summary 84
2.2. Introduction 86
2.3. Materials and methods 90
2.4. Results 106
2.4.1. Development of HTS-compatible assays 106
2.4.2. Screening for potent anti-osteoclastic plant extracts 107
2.4.3. Screening for potent osteogenic plant extracts 109
2.4.4. Selection of anti-osteoporotic plant extracts 110
2.4.5. Preventive effect of Edgeworthia papyrifera and D. genkwa extracts on ovariectomized mice 111
2.4.6. Therapeutic effect of E. papyrifera extract on ovariectomized rats 113
2.4.7. Identification of phytochemicals in E. papyrifera 119
2.4.8. Effect of phytochemicals on the activity of osteoclast and osteoblast 121
2.4.9. Identification and activity of purified Edgeworoside A 121
2.5. Discussion 124
Chapter 3. Whitening effect of Rhizoma arisaematis as functional cosmetic material 166
3.1. Summary 167
3.2. Introduction 168
3.3. Materials and methods 171
3.4. Results 178
3.4.1. Screening of potent anti-melanogenic plant extracts 178
3.4.2. Effect of R. Arisaematis on pigmentation in normal human epidermal melanocytes and human skin 178
3.4.3. Confirmation of anti-melanogenic effects in B16F1 cells 179
3.4.4. Role of R. Arisaematis in activation of autophagy in B16F1 cells 180
3.4.5. Effect of autophagy inhibition in R. Arisaematis-mediated anti-melanogenic activity in B16F1 cell 181
3.5. Discussion 183
Chapter 4. Conclusions and future directions 194
4.1. Conclusion of anti-osteoporotic natural products 195
4.2. Conclusion of whitening natural product 197
4.3. Future directions 198
References 199
국문 초록 218
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dc.formatapplication/pdf-
dc.format.extent4164418 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectMelanogenesis-
dc.subjectEdgeworthia papyrifera-
dc.subjectedgeworoside A-
dc.subjectosteoporosis-
dc.subjectosteoclast-
dc.subjectosteoblast-
dc.subjectovariectomized-
dc.subjectdrug candidate-
dc.subjectfunctional ingredients-
dc.subjectRhizoma arisaematis-
dc.subjectAutophagy-
dc.subject.ddc630-
dc.titleInvestigation of the anti-osteoporotic activity of Edgeworthia papyrifera and Edgeworoside A and anti-melanogenic activity of Rhizoma arisaematis-
dc.title.alternative삼지닥과 Edgeworoside A의 항골다공증 및 천남성의 미백 효과에 관한 연구-
dc.typeThesis-
dc.contributor.AlternativeAuthorPan-Soo Kim-
dc.description.degreeDoctor-
dc.contributor.affiliation농업생명과학대학 농생명공학부-
dc.date.awarded2018-02-
Appears in Collections:
College of Agriculture and Life Sciences (농업생명과학대학)Dept. of Agricultural Biotechnology (농생명공학부)Theses (Ph.D. / Sc.D._농생명공학부)
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