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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

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Authors
김판수
Advisor
서진호
Major
농업생명과학대학 농생명공학부
Issue Date
2018-02
Publisher
서울대학교 대학원
Keywords
MelanogenesisEdgeworthia papyriferaedgeworoside Aosteoporosisosteoclastosteoblastovariectomizeddrug candidatefunctional ingredientsRhizoma arisaematisAutophagy
Description
학위논문 (박사)-- 서울대학교 대학원 : 농업생명과학대학 농생명공학부, 2018. 2. 서진호.
Abstract
Natural 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.
Language
English
URI
https://hdl.handle.net/10371/140791
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College of Agriculture and Life Sciences (농업생명과학대학)Dept. of Agricultural Biotechnology (농생명공학부)Theses (Ph.D. / Sc.D._농생명공학부)
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