石榴皮化学成分研究
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摘要
【目的】研究石榴(Punica granatum L.)皮的化学成分及其抗补体活性。【方法】通过硅胶柱、Sephadex LH-20、RP-C18反相硅胶等色谱柱分离纯化,运用NMR和MS等波谱学方法鉴定化合物的结构,并采用抗补体经典途径溶血方法,测定石榴皮化学成分的抗补体活性。【结果】从石榴皮乙醇提取物的乙酸乙酯和正丁醇部分分离得到14个化合物,包括5个黄酮苷类,即山柰酚-3-O-β-d-吡喃葡萄糖苷(1)、槲皮素-3-O-β-d-吡喃葡萄糖苷(2)、山柰酚-3-O-β-d-吡喃木糖苷(3)、柚皮素-7-O-β-d-吡喃葡萄糖苷(4)和山柰酚-3-O-β-d-芸香糖苷(5),以及9个其他类型化合物,即5-羟甲基糠醛(6)、正丁基-O-β-d-吡喃果糖苷(7)、3, 3′-二甲基鞣花酸-4-O-β-d-吡喃葡萄糖苷(8)、roseoside (9)、3-O-(β-d-吡喃葡萄糖基)-1-(3-甲氧基-4-羟基苯基)-1-丙酮(10)、3-O-(β-d-吡喃葡萄糖基)-1-(3, 5-二甲氧基-4-羟基苯基)-1-丙酮(11)、5-羟甲基呋喃-3-羧酸(12)、(1′R, 3′S, 5′R, 8′S, 2Z,4E)-dihydrophaseic acid 3′-O-β-d-glucopyranoside (13)和没食子酸(14)。石榴皮乙酸乙酯部分有抗补体活性(100μg/mL时,抑制率为51.73%)。【结论】化合物3、4、7和9～13均为首次从石榴中分离得到,乙酸乙酯部分有抗补体活性,活性成分有待进一步阐明。本研究丰富了石榴的化学成分基础,为进一步开发利用石榴皮的药用价值提供了一定的实验依据。
[Purpose]To study the chemical constituents and their anti-complement activity from pomegranate(Punica granatum L.) peels. [Methods]Compounds were isolated and purified by column chromatography of silica gel, Sephadex LH-20 gel and RP-C18. And their structures were identified by spectral methods(MS and NMR). The anti-complement activity was determined by the hemolysis method of the complement classical pathway. [Results]Fourteen compounds were isolated and identified from the ethyl acetate and n-butanol fractions of the pomegranate peel ethanol extracts, including five flavonoid glycosides, kaempferol-3-O-β-d-glucopyranoside(1), quercetin-3-O-β-d-glucopyranoside(2), kaempferol-3-O-β-d-xylopyranoside(3), naringenin-7-O-β-d-glucopyranoside(4), and kaempferol-3-O-β-d-rutinoside(5), and nine other types of compounds, 5-hydroxymethylfurfural(6), n-butyl-O-β-d-fructopyranoside(7), 3, 3 ′-di-O-methylellagic acid 4-O-β-d-glucopyranose(8), roseoside(9), 3-O-(β-d-glucopyranosyl)-1-(3-methoxy-4-hydroxyphenyl)-1-propanone(10), 3-O-(β-d-glucopyranosyl)-1-(3, 5-dimethoxy-4-hydroxyphenyl)-1-propanone(11), 5-hydroxymethylfuran-3-carboxylic acid(12),(1′R, 3′S, 5′R, 8′S, 2 Z, 4 E)-dihydrophaseic acid 3′-O-β-d-glucopyranoside(13),and gallic acid(14). The ethyl acetate-soluble fraction possessed anti-complement activity with an inhibition rate of 51.73% at 100 μg/mL. [Conclusion]Compounds 3, 4, 7, and 9-13 were isolated from this plant for the first time. The ethyl acetate-soluble fraction had anti-complement activity,however, the active components need to be further clarified. This research enriched the chemical constituents of P. granatum and provided experimental evidences for further exploitation and utilization of medicinal value from pomegranate peels.
[Purpose]To study the chemical constituents and their anti-complement activity from pomegranate(Punica granatum L.) peels. [Methods]Compounds were isolated and purified by column chromatography of silica gel, Sephadex LH-20 gel and RP-C18. And their structures were identified by spectral methods(MS and NMR). The anti-complement activity was determined by the hemolysis method of the complement classical pathway. [Results]Fourteen compounds were isolated and identified from the ethyl acetate and n-butanol fractions of the pomegranate peel ethanol extracts, including five flavonoid glycosides, kaempferol-3-O-β-d-glucopyranoside(1), quercetin-3-O-β-d-glucopyranoside(2), kaempferol-3-O-β-d-xylopyranoside(3), naringenin-7-O-β-d-glucopyranoside(4), and kaempferol-3-O-β-d-rutinoside(5), and nine other types of compounds, 5-hydroxymethylfurfural(6), n-butyl-O-β-d-fructopyranoside(7), 3, 3 ′-di-O-methylellagic acid 4-O-β-d-glucopyranose(8), roseoside(9), 3-O-(β-d-glucopyranosyl)-1-(3-methoxy-4-hydroxyphenyl)-1-propanone(10), 3-O-(β-d-glucopyranosyl)-1-(3, 5-dimethoxy-4-hydroxyphenyl)-1-propanone(11), 5-hydroxymethylfuran-3-carboxylic acid(12),(1′R, 3′S, 5′R, 8′S, 2 Z, 4 E)-dihydrophaseic acid 3′-O-β-d-glucopyranoside(13),and gallic acid(14). The ethyl acetate-soluble fraction possessed anti-complement activity with an inhibition rate of 51.73% at 100 μg/mL. [Conclusion]Compounds 3, 4, 7, and 9-13 were isolated from this plant for the first time. The ethyl acetate-soluble fraction had anti-complement activity,however, the active components need to be further clarified. This research enriched the chemical constituents of P. granatum and provided experimental evidences for further exploitation and utilization of medicinal value from pomegranate peels.
引文
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[2]国家药典委员会.中华人民共和国药典:2010年版.一部[M].北京:中国医药科技出版社,2010.
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[13]倪付勇,刘露,宋亚玲,等.金银花中抗补体活性酚酸类成分的研究[J].中国中药杂志,2015,40(2):269.DOI:10.4268/cjcmm20150220.
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[20]SANG S M,CHENG X F,ZHU N Q,et al.Flavonol glycosides and novel iridoid glycoside from the leaves of Morinda citrifolia[J].Journal of Agricultural and Food Chemistry,2001,49(9):4478.DOI:10.1021/jf010492e.
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[26]YE G,PENG H,FAN M,et al.Ellagic acid derivatives from the stem bark of Dipentodon sinicus[J].Chemistry of Natural Compounds,2007,43(2):125.DOI:10.1007/s10600-007-0060-y.
[27]SHYAULA S L,CHOUDHARY M I,MANANDHARM D.Megastigmane,iridoid,benzyl alcohol and phenyl propanoid glycosides from the Nepalese sandalwood Osyris wightiana,Wall.ex Wight[J].Moscow University Chemistry Bulletin,2013,68(6):293.DOI:10.3103/S0027131413060047.
[28]XIANG Y,YANG S P,ZHAN Z J,et al.Terpenoids and phenols from Taiwania flousiana[J].Acta Botanica Sinica,2004,46(8):1002.
[29]郭蓉,王跃虎,石亚娜,等.云南金钱槭茎化学成分[J].天然产物研究与开发,2012,24(8):1007.DOI:10.3969/j.issn.1001-6880.2012.08.001.
[30]CABRERA G M,ROBERTI M J,WRIGHT J E,et al.Cryptoporic and isocryptoporic acids from the fungal cultures of Polyporus arcularius and P.ciliatus[J].Phytochemistry,2002,61(2):189.DOI:10.1016/S0031-9422(02)00221-2.
[31]JOUNG U,LEE J,NAM J W,et al.Identification of a new isomer of dihydrophaseic acid 3'-O-β-D-glucopyranoside from Nelumbo nucifera[J].Bulletin-Korean Chemical Society,2011,32(11):4083.DOI:10.5012/bkcs.2011.32.11.4083.
[32]林佳,李琰,徐丽珍.石榴叶的化学成分研究[J].中南药学,2005,3(2):70.DOI:10.3969/j.issn.1672-2981.2005.02.002.
[33]PARK H M,MOON E,KIM A J,et al.Extract of Punica granatum,inhibits skin photoaging induced by UVBirradiation[J].International Journal of Dermatology,2010,49(3):276.DOI:10.1111/j.1365-4632.2009.04269.x.
[34]陈伟,刘瑞,韩振斌,等.石榴皮的化学成分及药理作用[J].北京农业,2015(17):97.DOI:10.3969/j.issn.1000-6966.2015.17.081.
[35]徐小娜,陈亮宇,赵心清.天然抗补体活性物质研究进展[J].天然产物研究与开发,2015,27(2):355.DOI:10.16333/j.1001-6880.2015.02.031.
[2]国家药典委员会.中华人民共和国药典:2010年版.一部[M].北京:中国医药科技出版社,2010.
[3]热依木古丽·阿布都拉,来海中,马依努尔·拜克力,等.石榴皮化学成分及生物活性研究进展[J].新疆医科大学学报,2013,36(6):737.DOI:10.3969/j.issn.1009-5551.2013.06.004.
[4]王如峰,向兰,杜力军,等.石榴的化学成分[J].亚太传统医药,2006(3):61.
[5]JURENKA J.Therapeutic applications of pomegranate(Punica granatum L.):a review[J].Alternative Medicine Review,2008,13(2):128.
[6]KUMAR M S,TALAMBEDU U,VEENA P.A review on antihyperglycemic and antihepatoprotective activity of eco-friendly Punica granatum peel waste[J].Evidence-Based Complementary and Alternative Medicine,2013,2013:656172.DOI:10.1155/2013/656172.
[7]FISCHER U A,CARLE R,KAMMERER D R.Identification and quantification of phenolic compounds from pomegranate(Punica granatum L.)peel,mesocarp,aril and differently produced juices by HPLC-DAD-ESI/MS(n)[J].Food Chemistry,2011,127(2):807.DOI:10 .1016/j.foodchem.2010.12.156.
[8]LI Y F,GUO C J,YANG J J,et al.Evaluation of antioxidant properties of pomegranate peel extract in comparison with pomegranate pulp extract[J].Food Chemistry,2006,96(2):254.DOI:10.1016/j.foodchem.2005.02.033.
[9]ISMAIL T,SESTILI P,AKHTAR S.Pomegranate peel and fruit extracts:a review of potential anti-inflammatory and anti-infective effects[J].Journal of Ethnopharmacology,2012,143(2):397.DOI:10.1016/j.jep.2012.07.004.
[10]张杰,詹炳炎,姚学军,等.中药石榴皮鞣质成分抗生殖器疱疹病毒作用[J].中国中药杂志,1995,20(9):556.DOI:10.3321/j.issn:1001-5302.1995.09.014.
[11]吕琴,刘金宝.石榴皮醇提物对小鼠体液免疫功能的影响[J].新疆医科大学学报,2007,30(5):484.DOI:10.3969/j.issn.1009-5551.2007.05.019.
[12]GRACIOUS R R,SELVASUBRAMANIAN S,JAY-ASUNDAR S.Immunomodulatory activity of Punica granatum in rabbits-a preliminary study[J].Journal of Ethnopharmacology,2001,78(1):85.DOI:10.1016/S0378-8741(01)00287-2.
[13]倪付勇,刘露,宋亚玲,等.金银花中抗补体活性酚酸类成分的研究[J].中国中药杂志,2015,40(2):269.DOI:10.4268/cjcmm20150220.
[14]SUN Q Y,BAO J.Purification,cloning and characterization of a metalloproteinase from Naja atra venom[J].Toxicon,2010,56(8):1459.DOI:10.1016/j.toxicon.2010.08.013.
[15]DRESEL M,DUNKEL A,HOFMANN T.Sensomics analysis of key bitter compounds in the hard resin of hops(Humulus lupulus L.)and their contribution to the bitter profile of Pilsner-type beer[J].Journal of Agricultural and Food Chemistry,2015,63(13):3402.DOI:10.1021/acs.jafc.5b00239.
[16]李敏,高慧媛,孙博航,等.茶叶正丁醇萃取物化学成分的分离与鉴定[J].沈阳药科大学学报,2008(10):785.DOI:10.14066/j.cnki.cn21-1349/r.2008.10.005.
[17]KIM J S,KWON Y S,SA Y J,et al.Isolation and identification of sea buckthorn(Hippophae rhamnoides)phenolics with antioxidant activity andα-glucosidase inhibitory effect[J].Journal of Agricultural and Food Chemistry,2011,59(1):138.DOI:10.1021/jf103130a.
[18]WANG P H,LEE S S.Polar chemical constituents from Phoebe formosana[J].Journal of the Chinese Chemical Society,1999,46(2):215.DOI:10.1002/jccs.199900034.
[19]ZEKRY S H,ZAYED R A,RADWAN M M,et al.Effect of metabolites isolated from Cuscuta pedicellata on high fat diet-fed rats[J].Medicinal Chemistry Research,2015,24(5):1964.DOI:10.1007/s00044-014-1269-5.
[20]SANG S M,CHENG X F,ZHU N Q,et al.Flavonol glycosides and novel iridoid glycoside from the leaves of Morinda citrifolia[J].Journal of Agricultural and Food Chemistry,2001,49(9):4478.DOI:10.1021/jf010492e.
[21]李燕,王春兰,王芳菲,等.铁皮石斛化学成分的研究[J].中国中药杂志,2010,35(13):1715.DOI:10.4268/cjcmm20101314.
[22]HEARN M.Carbon-13 chemical shifts in some substituted furans and thiophens[J].Australian Journal of Chemistry,1976,29(1):107.DOI:10.1071/CH9760107.
[23]李帅,匡海学,冈田嘉仁,等.鬼针草有效成分的研究(Ⅱ)[J].中草药,2004,35(9):972.DOI:10.3321/j.issn.0253-2670.2004.09.005.
[24]ZHANG C Z,XU X Z,LI C.Fructosides from Cynomorium songaricum[J].Phytochemistry,1996,41(3):975.DOI:10.1016/0031-9422(95)00705-9.
[25]邓可众,熊英,周斌,等.猫爪草化学成分的分离与结构鉴定[J].中国实验方剂学杂志,2013,19(24):132.DOI:10.11653/syfj2013240132.
[26]YE G,PENG H,FAN M,et al.Ellagic acid derivatives from the stem bark of Dipentodon sinicus[J].Chemistry of Natural Compounds,2007,43(2):125.DOI:10.1007/s10600-007-0060-y.
[27]SHYAULA S L,CHOUDHARY M I,MANANDHARM D.Megastigmane,iridoid,benzyl alcohol and phenyl propanoid glycosides from the Nepalese sandalwood Osyris wightiana,Wall.ex Wight[J].Moscow University Chemistry Bulletin,2013,68(6):293.DOI:10.3103/S0027131413060047.
[28]XIANG Y,YANG S P,ZHAN Z J,et al.Terpenoids and phenols from Taiwania flousiana[J].Acta Botanica Sinica,2004,46(8):1002.
[29]郭蓉,王跃虎,石亚娜,等.云南金钱槭茎化学成分[J].天然产物研究与开发,2012,24(8):1007.DOI:10.3969/j.issn.1001-6880.2012.08.001.
[30]CABRERA G M,ROBERTI M J,WRIGHT J E,et al.Cryptoporic and isocryptoporic acids from the fungal cultures of Polyporus arcularius and P.ciliatus[J].Phytochemistry,2002,61(2):189.DOI:10.1016/S0031-9422(02)00221-2.
[31]JOUNG U,LEE J,NAM J W,et al.Identification of a new isomer of dihydrophaseic acid 3'-O-β-D-glucopyranoside from Nelumbo nucifera[J].Bulletin-Korean Chemical Society,2011,32(11):4083.DOI:10.5012/bkcs.2011.32.11.4083.
[32]林佳,李琰,徐丽珍.石榴叶的化学成分研究[J].中南药学,2005,3(2):70.DOI:10.3969/j.issn.1672-2981.2005.02.002.
[33]PARK H M,MOON E,KIM A J,et al.Extract of Punica granatum,inhibits skin photoaging induced by UVBirradiation[J].International Journal of Dermatology,2010,49(3):276.DOI:10.1111/j.1365-4632.2009.04269.x.
[34]陈伟,刘瑞,韩振斌,等.石榴皮的化学成分及药理作用[J].北京农业,2015(17):97.DOI:10.3969/j.issn.1000-6966.2015.17.081.
[35]徐小娜,陈亮宇,赵心清.天然抗补体活性物质研究进展[J].天然产物研究与开发,2015,27(2):355.DOI:10.16333/j.1001-6880.2015.02.031.