현초에서 분리된 페놀성 화합물들의 흰쥐 수정체 유래 알도즈 환원효소 및 갈락티톨 생성 억제 효과
Inhibitory Effect of the Phenolic Compounds from Geranium thunbergii on Rat Lens Aldose Reductase and Galactitol Formation
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초록
We evaluated the inhibitory effects of extracts and components of Geranium thunbergii on aldose reductase (AR) and galactitol formation in rat lenses with high levels of galactose as a part of our ongoing search of natural sources for therapeutic and preventive agents for diabetic complications. The inhibitory effects of water, methanol and ethanol extracts of G. thunbergii on rat lens AR (RLAR) were determined. Comparing inhibitory effects of various solvent extracts, ethanol extract showed RLAR inhibitory activity (IC50 values, 5.24 and 6.39㎍/㎖, respectively). The ethanol extract was fractionated to chloroform, ethyl acetate and water. Of these, the ethyl acetate fraction from ethanol extract of G. thunbergii exhibited RLAR inhibitory activity (IC50 value, 2.64㎍/㎖). In order to identify the bioactive components of ethyl acetate soluble fraction of ethanol extract from G. thunbergii, eight compounds, namely gallic acid (1), protocatechuic acid (2), p-hydroxybenzoic acid (3), brevifolin carboxylic acid (4), geraniin (5), ellagic acid (6), kaempferol-3-O-arabinofuranosyl-7-O-rhamnopyranoside (7), kaempferitrin (8) were isolated. The isolates were subjected to in vitro bioassays to evaluate their inhibitory activity on RLAR and galactitol formation in rat lenses. The ellagic tannins (5, 6) and flavonoid (7) exhibited strong inhibitory effects on RLAR. Also, these three compounds (5, 6 and 7) suppressed galactitol accumulation in rat lens under high galactose conditions, demonstrating the potential to prevent galactitol accumulation exo vivo. These results suggest that the extracts and components of G. thunbergii are a promising agent in the prevention or treatment of diabetic complications.
Abstract
We evaluated the inhibitory effects of extracts and components of Geranium thunbergii on aldose reductase (AR) and galactitol formation in rat lenses with high levels of galactose as a part of our ongoing search of natural sources for therapeutic and preventive agents for diabetic complications. The inhibitory effects of water, methanol and ethanol extracts of G. thunbergii on rat lens AR (RLAR) were determined. Comparing inhibitory effects of various solvent extracts, ethanol extract showed RLAR inhibitory activity (IC50 values, 5.24 and 6.39㎍/㎖, respectively). The ethanol extract was fractionated to chloroform, ethyl acetate and water. Of these, the ethyl acetate fraction from ethanol extract of G. thunbergii exhibited RLAR inhibitory activity (IC50 value, 2.64㎍/㎖). In order to identify the bioactive components of ethyl acetate soluble fraction of ethanol extract from G. thunbergii, eight compounds, namely gallic acid (1), protocatechuic acid (2), p-hydroxybenzoic acid (3), brevifolin carboxylic acid (4), geraniin (5), ellagic acid (6), kaempferol-3-O-arabinofuranosyl-7-O-rhamnopyranoside (7), kaempferitrin (8) were isolated. The isolates were subjected to in vitro bioassays to evaluate their inhibitory activity on RLAR and galactitol formation in rat lenses. The ellagic tannins (5, 6) and flavonoid (7) exhibited strong inhibitory effects on RLAR. Also, these three compounds (5, 6 and 7) suppressed galactitol accumulation in rat lens under high galactose conditions, demonstrating the potential to prevent galactitol accumulation exo vivo. These results suggest that the extracts and components of G. thunbergii are a promising agent in the prevention or treatment of diabetic complications.
참고문헌 (33)
- Carper DA, "Residues affecting the catalysis and inhibition of rat lens aldose reductase", Biochimica et Biophysica Acta, 1246, pp.67~63 (1995)
- 최혜정, "사방오리나무 추출물의 α-amylase 및 α-glucosidase 저해활성", 생명과학회지, 18(7), pp.1005~1010 (2008), 한국생명과학회
- Collins JG, "Aldose reductase and sorbitol dehydrogenase distribution in substructures of normal and diabetic rat lens", Investigative Ophthalmology Visual Science, 16, pp.242~243 (1977)
- Constantino L, "Diabetes complications and their potential prevention: aldose reductase inhibition and other approaches", Medical Care Research Review, 19, pp.3~23 (1999)
- Corns CM, "Herbal remedies and clinical biochemistry", Annals of Clinical Biochemistry, 40, pp.489~507 (2003)
- Dvornik E, "Polyol accumulation in galactosemic and diabetic rats: control by an aldose reductase inhibitor", Science, 182, pp.1146~1148 (1973)
- Fatmawati S, "The inhibitory effect on aldose reductase by an extract of Ganoderma lucidum", Phytotherapy Research, 23, pp.28~32 (2009)
- Gabbay KH, "The sorbitol pathway: Enzyme localization and content in normal and diabetic nerve and cord", Diabetes, 17, pp.239~243 (1968)
- Hayman S, "Isolation and properties of lens aldose reductase", Journal of Biological Chemistry, 240, pp.877~882 (1965)
- 전윤희, "Streptozotocin으로 유발한 당뇨병성 쥐에서의 당뇨병성 백내장과 망막병증에 대한 구기자와 황기 혼합 추출물 등의 면역 조절 및 예방 효과", 한국약용작물학회지, 18(1), pp.15~21 (2010), 한국약용작물학회
- Kato A, "Inhibitory effect of rhetsinine isolated from Evodia rutaecarpa on aldose reductase activity", Phytomedicine, 16, pp.258~261 (2009)
- Kim JK, "Inhibition of aldose reductase by phenylethanoid glycoside isolated from the seeds of Paulownia coreana", Biological Pharmaceutical Bulletin, 34, pp.160~163 (2011)
- 김선하, "Inhibitory Effect of quercetin-3-O-α-L-rhamnopyranoside from Chamaecyparis obtuse on Aldose Reductase and Sorbitol Accumulation", 한국약용작물학회지, 18(5), pp.305~310 (2010), 한국약용작물학회
- Kitagawa K, "Solution syntheses of two enkephalin-containing peptides E and dynorphin(1-24), using Nin-(2,4,6-triisopropylphenylsulfonyl) trytophan", Chemical Pharmaceutical Bulletin, 37, pp.2631~2638 (1989)
- Kubo M, "Studies of anti-cataract drugs from natural sources. I. Effects of a methanolic extract and the alkaloidal components from Corydalis tuber on in vitro aldose reductase activity", Biological Pharmaceutical Bulletin, 17, pp.458~459 (1994)
- Kwon OG, "Isolation of anti-microbial components from Montan cortex", Journal of Korean Pharmaceutical, 30, pp.340~344 (1999)
- Lee YS, "Inhibitory constituents of aldose reductase in the fruiting body of Phellinus linteus", BIOLOGICAL & PHARMACEUTICAL BULLETIN, 31, pp.765~768 (2008), PHARMACEUTICAL SOC JAPAN
- Lee YS, "Aldose Reductase Inhibitory Compounds from Glycyrrhiza uralensis", BIOLOGICAL & PHARMACEUTICAL BULLETIN, 33, pp.917~921 (2010), PHARMACEUTICAL SOC JAPAN
- Yeon Sil Lee, "Inhibitory Effect of Glucodistylin from the Bark of Quercus acutissima on Human Recombinant Aldose Reductase and Sorbitol Accumulation", Archives of Pharmacal Research, 34(2), pp.211~215 (2011), 대한약학회
- 임순성, "Rat lens aldose reductase inhibitory constituents of Nelumbo nucifera stamens", PHYTOTHERAPY RESEARCH, 20, pp.825~830, JOHN WILEY & SONS LTD
- Qing-He Liu, "A New Furofuran Lignan from Geranium thunbergii Sieb. et Zucc.", Archives of Pharmacal Research, 29(12), pp.1109~1113 (2006), 대한약학회
- Mulinacci N, "Flavonol glycosides from Sedum telephium subspecies maximum leaves", Phytochemistry, 38, pp.531~533 (1995)
- Nawwar MAM, "NMR spectral analysis of polyphenols from Punica granatum", Phytochemistry, 36, pp.793~768 (1994)
- Park WY, "Phenolic compounds from Acalypha australis L", Journal of Korean Pharmaceutical, 24, pp.20~25 (1993)
- Saijo R, "Gallic acid esters of bergenin and norbergenin from Mallotus japonicuc", Phytochemistry, 29, pp.267~270 (1990)
- Shin KH, "Effects of furanocoumarins from Angelica dahurica on aldose reductase and galactosemic cataract formation in rats", Archives of Pharmacal Research, 17, pp.331~336 (1994)
- Son KH, "A sensitive assay of red blood cell sorbitol level by high performance liquid chromatography: potential for diagnostic evaluation of diabetes", Clinica Chimica Acta, 354, pp.41~47 (2005)
- Srivastava Y, "Effect of Momordica charantia Linn. pomous aqueous extract on cataractogenesis in murrin alloxan diabetics", Pharmacological Research Communication, 20, pp.201~209 (1988)
- Tapsell LC, "Health benefits of herbs and spices: the past, the present, the future", Medical Journal of Australia, 185, pp.S4~S24 (2006)
- Ushio Y, "Effects of geraniin on morphology and function of macrophages", International Archives of Allergy and Immunology, 96, pp.224~230 (1991)
- Varma SD, "Flavonoids as inhibitors of lens aldose reductase", Science, 188, pp.1215~1216 (1975)
- Yisida T, "Tannins and related polyphenols of euphobiaceous plants,. Hydorlyzable tannins with 1C-glucose core from Phyllanthus flexuosus Muell", Arg. Chemical Pharmaceutical Bulletin, 40, pp.520~521 (1992)
- Yonekura-Sakakibara K, "Comprehensive flavonol profiling and transcriptome coexpression analysis leading to decoding genemetabolite correlations in Arabidopsis", The Plant Cell, 20, pp.2160~2176 (2008)