• 약학회지
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• 제46권5호
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• pp.295-300
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• 2002

To observe the structure-activity relationship of lupane derivatives both on cytotoxic and antiangiogenic activity, twelve lupane derivatives were prepared; their antiangiogenic and cytotoxic activities were evaluated. Among them, four compounds were more cytotoxic than betulinic acid. Carboxylic acid at C28 seemed to be essential for cytotoxic activity. But, a selective cytotoxicity toward SK-MEL-2 was not observed. As for antiangiogenic activity, none of the compounds except lupeol showed antiangiogenic activity at 30 $\mu\textrm{g}$/mL.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.130.2-130.2
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• 2003

Betulinic acid (BA), a pentacyclic triterpene isolated from Lycopus lucidus, has been reported to be a selective inducer of apoptosis in various human tumor cells. It also exhibits anti-inflammatory and immunomodulatory properties. Due to its high level of these activities and lack of toxicity, BA is an attractive and promising compound as a new drug and recently undergoing preclinical development as an immunomodulators. How BA mediates these matters is not known yet. (omitted)

• Nutrition Research and Practice
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• 제8권5호
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• pp.509-515
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• 2014

BACKGROUND/OBJECTIVES: The root of Vitis amurensis Ruprecht, a sort of wild-growing grape, has been used in oriental medicine for treatment of skin ailments; however, its dermatological activity is not sufficiently understood. The aim of this study was to investigate tyrosinase inhibitory and anti-melanogenic activities of V. amurensis Ruprecht root methanol extract (VARM) in B16F10 mouse melanoma cells and to attempt to isolate and identify the active compound issued from VARM. MATERIALS/METHODS: Anti-melanogenic activity of VARM was analyzed in ${\alpha}$-melanocyte stimulating hormone (MSH)-stimulated B16F10 cells through evaluation of antioxidative activity as well as inhibited tyrosinase activity and melanin contents compared with those of kojic acid and arbutin. After anti-melanogenic analysis of VARM, serial fractionation, nuclear magnetic resonance (NMR), and thin layer chromatorgraphy (TLC) were applied for identification of active compounds contained in VARM. RESULTS: VARM significantly inhibited oxidative stress and tyrosinase activity and attenuated ${\alpha}$-MSH-induced melanin production in B16F10 cells. For isolation of active compounds, VARM was fractionated using a series of organic solvents, including dichloromethane ($CH_2Cl_2$), ethyl acetate (EtOAc), and n-butanol (n-BuOH). Among fractions showing anti-melanogenic activity, the CH2Cl2 fraction induced the most potent attenuation of melanogenesis without cytotoxicity and the major compound in the $CH_2Cl_2$ fraction was identified as betulinic acid. Betulinic acid isolated from the $CH_2Cl_2$ fraction of VARM significantly attenuated ${\alpha}$-MSH-induced melanogenesis in a dose dependent manner, which was stronger than that of arbutin used as a positive control. CONCLUSIONS: These results indicate that VARM inhibits oxidative stress, tyrosinase activity, and ${\alpha}$-MSH-induced melanogenesis in B16F10 cells, due primarily to the active compound, betulinic acid, in the $CH_2Cl_2$ fraction.

• 대한약침학회지
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• 제19권1호
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• pp.37-44
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• 2016

Objectives: This study examined the relative efficacies of a derivative of betulinic acid (dBA) and its poly (lactide-co-glycolide) (PLGA) nano-encapsulated form in A549 lung cancer cells in vivo and in co-mutagen [sodium arsenite (SA) + benzo[a]pyrene (BaP)]-induced lung cancer in mice in vivo. Methods: dBA was loaded with PLGA nanoparticles by using the standard solvent displacement method. The sizes and morphologies of nano-dBA (NdBA) were determined by using transmission electron microscopy (TEM), and their intracellular localization was verified by using confocal microscopy. The binding and interaction of NdBA with calf thymus deoxyribonucleic acid (CT-DNA) as a target were analyzed by using conventional circular dichroism (CD) and melting temperature (Tm) profile data. Apoptotic signalling cascades in vitro and in vivo were studied by using an enzyme-linked immunosorbent assay (ELISA); the ability of NdBA to cross the blood-brain barrier (BBB) was also examined. The stage of cell cycle arrest was confirmed by using a fluorescence-activated cell-sorting (FACS) data analysis. Results: The average size of the nanoparticles was ~ 110 nm. Confocal microscopy images confirmed the presence of NdBA in the cellular cytoplasm. The bio-physical properties of dBA and NdBA ascertained from the CD and the Tm profiles revealed that NdBA had greater interaction with the target DNA than dBA did. Both dBA and NdBA arrested cell proliferation at G0/G1, NdBA showing the greater effect. NdBA also induced a greater degree of cytotoxicity in A549 cells, but it had an insignificant cytotoxic effect in normal L6 cells. The results of flow cytometric, cytogenetial and histopathological studies in mice revealed that NdBA caused less nuclear condensation and DNA damage than dBA did. TEM images showed the presence of NdBA in brain samples of NdBA fed mice, indicating its ability to cross the BBB. Conclusion: Thus, compared to dBA, NdBA appears to have greater chemoprotective potential against lung cancer.

• Biomolecules & Therapeutics
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• 제25권6호
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• pp.618-624
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• 2017

Betulinic acid (BA), a natural pentacyclic triterpene found in many medicinal plants is known to have various biological activity including tumor suppression and anti-inflammatory effects. In this study, the cell-death induction effect of BA was investigated in BV-2 microglia cells. BA was cytotoxic to BV-2 cells with $IC_{50}$ of approximately $2.0{\mu}M$. Treatment of BA resulted in a dose-dependent chromosomal DNA degradation, suggesting that these cells underwent apoptosis. Flow cytometric analysis further confirmed that BA-treated BV-2 cells showed hypodiploid DNA content. BA treatment triggered apoptosis by decreasing Bcl-2 levels, activation of capase-3 protease and cleavage of PARP. In addition, BA treatment induced the accumulation of p62 and the increase in conversion of LC3-I to LC3-II, which are important autophagic flux monitoring markers. The increase in LC3-II indicates that BA treatment induced autophagosome formation, however, accumulation of p62 represents that the downstream autophagy pathway is blocked. It is demonstrated that BA induced cell death of BV-2 cells by inducing apoptosis and inhibiting autophagic flux. These data may provide important new information towards understanding the mechanisms by which BA induce cell death in microglia BV-2 cells.

• Archives of Pharmacal Research
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• 제26권12호
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• pp.1087-1095
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• 2003

Betulinic acid (BA), a pentacyclic triterpene isolated from Lycopus lucidus, has been reported to be a selective inducer of apoptosis in various human cancer and shown anti-inflammatory and immunomodulatory properties. We postulated that BA modulates the immunomodulatory properties at least two groups of protein mediators of inflammation, interlukin-1$\beta$ (IL-1$\beta$) and the tumor necrosis factor- $\alpha$ (TNF-$\alpha$) on the basis of the critical role of the monocytes and tissue macrophages in inflammatory and immune responses. TNF-$\alpha$ and IL-1$\beta$ were produced by BA in a dose dependent manner at concentration of 0.625 and 10 $\mu$g/mL. The production of NO associated with iNOS was inhibited when treated with LPS at the concentration of 2.5 to 20 $\mu$g/mL of BA whereas COX-2 expression was decreased at 2.5 to 20 $\mu$g/mL. These modulations of inflammatory mediators were examined in LPS-stimulated RAW 264.7 cells and peritoneal macrophages. The morphology of macrophage was also examined and enhanced surface CD 40 molecule was expressed when treated BA at 0.625∼5 $\mu$g/mL with or without LPS. Furthermore, BA (20 $\mu$g/mL) enhanced apoptosis by producing DNA ladder in the RAW 264.7 cells. Our results indicated that BA induced activation of macrophage and pro-inflammatory cytokines. This may provide a molecular basis for the ability of BA to mediate macrophage, suppress inflammation, and modulate the immune response.

• Journal of Applied Biological Chemistry
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• 제57권4호
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• pp.359-363
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• 2014

털부처꽃(Lythrum salicaria L.) 뿌리는 실온에서 80% MeOH로 추출하고 이 추출물을 EtOAc 분획, n-BuOH 분획, $H_2O$ 분획으로 나누었다. 2,2-dipicryl-1-phenylhydrazyl (DPPH) radical 소거능을 이용한 항산화 활성을 측정하여 활성 추적 분획(Activity guided fractionation)에 따라 항산화 활성이 높은 EtOAc 분획에 대하여 silica gel 및 octadecyl $SiO_2$ column chromatography를 반복하여 항산화 활성을 나타내는 화합물 1과 major 화합물 2 및 3을 분리, 정제하였다. NMR, IR, 및 MS 등의 spectrum을 해석하여, Myricetin-3-O-${\beta}$-D-glucopyranoside (1), oleanolic acid (2) 및 betulinic acid (3)로 구조를 결정하였다. 화합물 1은 DPPH radical 소거능을 이용한 항산화 활성을 측정 한 결과 $25{\mu}g/mL$ 농도에서 $74.47{\pm}1.64%$의 저해 값을 가지는 것으로 나타났다.

• Journal of the Korean Wood Science and Technology
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• 제33권1호통권129호
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• pp.58-62
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• 2005

우리나라의 가로수로 널리 분포되어 있는 수종인 플라타너스에 생리활성이 우수한 천연물인 베출린산(BA)을 대량생산할 수 있는지를 알아보기 위하여 본 연구를 수행하였다. 서울과 경기도의 여러지역의 가로수를 대상으로 시료를 계절별로 채집하여 기건하여 분쇄한 시료를 메탄올로 추출하여 그 추출물을 농축하여 얻고 크로로포름으로 분획하여 BA fraction을 얻은 후, HPLC로 베출린산의 함량을 측정하였다. 그 결과, 여러 지역에서 채집하여 분석한 대부분의 플라타너스 수종이 상당량의 베출린산을 함유하고 있으며 11월 말경이 BA를 대량 얻기 위한 최적의 시기로 확인하였다.

• Natural Product Sciences
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• 제10권3호
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• pp.93-95
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• 2004

Eleven triterpenoids, colubrinic acid (1), alphitolic acid (2), 3-O-cis-p-coumaroyl alphitolic acid (3), 3-O-trans-p-coumaroyl alphitolic acid (4), 3-O-cis-p-coumaroyl maslinic acid (5), 3-O-trans-p-coumaroyl maslinic acid (6), betulinic acid (7), oleanolic acid (8), betulonic acid (9), oleanonic acid (10), and zizyberenalic acid (11), were isolated from the fruits of Zizyphus jujuba Mill. A simple and rapid HPLC method, using a $C_{18}$ column, has been developed for the quantitative analysis of these compounds 1 (0.74%),2 (0.09%), 3 (0.19%), 4 (0.19%), 5 (0.08%),6 (0.08%), 7 (0.41%), 8 (0.05%), 9 (0.50%),10 (0.59%), and 11 (0.19%).

• Applied Biological Chemistry
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• 제51권4호
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• pp.316-320
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• 2008

과육을 제거한 산수유 씨의 MeOH 추출물의 EtOAc 분획물로부터 이용하여 10종의 화합물을 분리하였다. 이들 중에서 (+)- pinoresinol, (-)-balanophonin, vanillin, 4-hydroxybenzaldehyde, coniferaldehyde, betulinic acid는 이 식물에서 처음으로 분리된 물질들이다. 본 연구에서 분리된 10종의 화합물에 대한 in vitro 최종당화산물(AGEs) 생성억제효능 실험결과, (-)-balanophonin (화합물 2)과 gallicin(화합물 3)이 각각 $IC_{50}$ 값 27.81과 18.04${\mu}M$로 비교양성대조군인 aminoguanidine(974.59 ${\mu}M$)보다 훨씬 우수한 효능을 나타내었다.