趙維,韓華銳,趙雅嬋,尚志強(qiáng)*,呂麗娟*
(1.天津農(nóng)學(xué)院 基礎(chǔ)科學(xué)學(xué)院,天津 300384;2.包頭醫(yī)學(xué)院,內(nèi)蒙古 包頭 014060)
天然活性成分雛菊葉龍膽酮的研究進(jìn)展△
趙維1,韓華銳2,趙雅嬋1,尚志強(qiáng)1*,呂麗娟1*
(1.天津農(nóng)學(xué)院 基礎(chǔ)科學(xué)學(xué)院,天津 300384;2.包頭醫(yī)學(xué)院,內(nèi)蒙古 包頭 014060)
雛菊葉龍膽酮;植物分布;藥理活性;進(jìn)展
圖1 雛菊葉龍膽酮結(jié)構(gòu)式
表1 雛菊葉龍膽酮在植物中的分布
表1(續(xù))
雖然雛菊葉龍膽酮在藥用植物中分布廣泛,但是其在植物中的含量比較低。截止目前,有關(guān)雛菊葉龍膽酮的制備方法多為溶劑萃取(或同時(shí)輔以超聲等手段),再借助多種分離介質(zhì),如HP-20樹(shù)脂、大孔吸附樹(shù)脂、硅膠、葡聚糖凝膠以及制備液相色譜、高速逆流色譜(HSCCC)等技術(shù)[56]來(lái)實(shí)現(xiàn)其提取分離和純化。其中HSCCC法作為一種液-液分配色譜技術(shù),無(wú)需固體支撐載體,避免了因不可逆吸附而造成的樣品損失,有著廣闊的應(yīng)用空間。
目前,該化合物的制備仍然局限于從植物中提取分離而制得,未見(jiàn)有關(guān)其生物合成或化學(xué)全合成的報(bào)道。在現(xiàn)有技術(shù)中,劉東鋒等[57]提出自己的制備方法,該方法適用于雛菊葉龍膽酮的產(chǎn)業(yè)化放大。其具體做法:將尖葉假龍膽(G.acuta)以70%~90%丙酮溶液超聲提取,提取液回收試劑經(jīng)大孔樹(shù)脂吸附,分別用40%~50%、70%甲醇溶液洗脫,得粗提物,再用高速逆流色譜儀分離。
自上述藥用植物中制備得到的雛菊葉龍膽酮,其結(jié)構(gòu)確證方法多用紫外光譜(UV)、紅外光譜(IR)、質(zhì)譜(MS)、氫譜(1HNMR)、碳譜(13CNMR)、二維核磁共振譜(2D-NMR)等技術(shù),僅有個(gè)別文獻(xiàn)[58]采用了單晶X射線衍射法(SXRD)。其檢測(cè)及質(zhì)量評(píng)價(jià)多采用HPLC法,少量報(bào)道采用高效液相色譜-電噴霧電離-多級(jí)質(zhì)譜聯(lián)用(HPLC-ESI-MSn)技術(shù)[52]、基于1H-NMR代謝物組學(xué)技術(shù)[59]完成化合物的檢測(cè)分析。
研究表明,雛菊葉龍膽酮具有廣泛的生物學(xué)活性。
3.1 降血糖作用
Tian等[64]發(fā)現(xiàn),日本獐牙菜(S.japonica)的醇提物具有降血糖作用;紫紅獐牙菜(S.punicea)提取物對(duì)由各因素引起的高血糖均有一定的抑制作用,其中雛菊葉龍膽素通過(guò)抑制G-6-P活性,能明顯地降低空腹血糖,改善口服糖耐量,降低空腹血清胰島素。實(shí)驗(yàn)結(jié)果表明,雛菊葉龍膽素可降低血清總膽固醇(TC)、低密度脂蛋白膽固醇(LDL)和甘油三脂(TG),升高高密度脂蛋白膽固醇(HDL),通過(guò)增強(qiáng)胰島素信號(hào)轉(zhuǎn)導(dǎo),改善胰島素抵抗,增加肝糖原,降低葡萄糖激酶活性,增加葡萄糖-6-磷酸酯酶活性。雛菊葉龍膽素不僅能夠有效地治療Ⅱ型糖尿病,而且可以有效地改善機(jī)體對(duì)胰島素的耐受性[65]。
文莉[66]考察了湖北麥冬[Liriopespicata(Thunb.)Lour.var.proliferaY.T.Ma]多糖與雛菊葉龍膽酮配伍對(duì)STZ小鼠空腹血糖和糖耐量的作用。結(jié)果表明,二者均有降血糖活性,但兩者間無(wú)明顯協(xié)同作用。同時(shí),采用逆轉(zhuǎn)錄-聚合酶鏈反應(yīng)(RT-PCR)技術(shù)探究了雛菊葉龍膽酮的胰島素抵抗機(jī)理。結(jié)果表明,雛菊葉龍膽酮在過(guò)氧化物酶體增殖物激活受體γmRNA(PPARγmRNA)表達(dá)中未見(jiàn)明顯促進(jìn)PPARγmRNA表達(dá)的作用,其降低血糖活性與PPARγ無(wú)明顯關(guān)系。
3.2 抗氧化作用
3.3 抗菌作用
Saeed等[28]發(fā)現(xiàn),雛菊葉龍膽酮對(duì)5種革蘭陽(yáng)性菌(巨大芽孢桿菌、枯草芽孢桿菌、蘇云金芽孢桿菌、藤黃八疊球菌和金黃色葡萄球菌)、4種革蘭陰性菌(大腸桿菌、克雷伯肺炎菌、變形桿菌和假單胞菌)以及黑曲霉等8種真菌均有不同程度的抑制作用。
3.4 抗病毒及保肝作用
雛菊葉龍膽酮體外抗乙肝病毒實(shí)驗(yàn)表明,其對(duì)2215細(xì)胞的乙型肝炎表面抗原(HBsAg)表達(dá)有抑制作用,半數(shù)抑制濃度(IC50)為13 μg·mL-1,選擇指數(shù)(SI)為6.8,而對(duì)2215細(xì)胞DNA無(wú)明顯抑制作用[72-73]。Cao等[74]發(fā)現(xiàn),從川西獐牙菜(S.mussotii)中提取的雛菊葉龍膽酮也具有明顯的乙型肝炎表面抗原HBsAg(IC50>0.98 mM)和乙型肝炎e抗原(HBeAg)(IC50=0.35 mM)作用。
體外毒性及保肝活性實(shí)驗(yàn)表明,雛菊葉龍膽酮具有保護(hù)人肝癌細(xì)胞系HepG2細(xì)胞活性[75],通過(guò)增加谷胱甘肽的含量、減少氫氧自由基[45,47]和明顯地抑制谷丙轉(zhuǎn)氨酶(GPT)的活性[76-77],減輕對(duì)乙酰氨基酚誘導(dǎo)的藥源性HepG2肝細(xì)胞損傷。
3.5 膽堿酯酶抑制作用
3.6 單胺氧化酶抑制作用
單胺氧化酶(MAO)是一種與神經(jīng)系統(tǒng)中生物單胺的代謝有關(guān)的酶。體外實(shí)驗(yàn)發(fā)現(xiàn),雛菊葉龍膽酮是MAO的有效抑制劑,有望在治療抑郁、精神分裂等精神疾病中發(fā)揮作用[5,80-85]。
3.7 心血管系統(tǒng)的作用
武海軍等[86]研究了雛菊葉龍膽酮對(duì)正常大鼠心率及心電圖的影響。結(jié)果表明,大鼠心率隨雛菊葉龍膽酮?jiǎng)┝吭黾佣鴾p慢;P波時(shí)間和P波電壓略有抬高,心房到心室傳導(dǎo)所需時(shí)間(P-R)間期明顯縮短,心室除極和復(fù)極的全過(guò)程所需時(shí)間(Q-T)間期在大劑量組(0.024 mg·kg-1)、中劑量組(0.012 mg·kg-1)延長(zhǎng),而小劑量組(0.006 mg·kg-1)無(wú)明顯變化,心室除極(QRS)時(shí)限隨劑量增加而延長(zhǎng)。
李旻輝等[87]采用維拉帕米作為陽(yáng)性對(duì)照組,研究雛菊葉龍膽酮對(duì)氯化鋇致大鼠心律失常的防治作用。結(jié)果表明,與對(duì)照組相比,3個(gè)劑量組(0.05、0.025、0.0125 mg·kg-1)均使大鼠心律失常發(fā)生時(shí)間推遲,嚴(yán)重程度減輕,并且0.05、0.025 mg·kg-1劑量組心律失常持續(xù)時(shí)間明顯縮短。
3.8 對(duì)缺血性腦損傷的保護(hù)作用
宋慧君等[88]研究雛菊葉龍膽酮對(duì)小鼠永久性、完全性全腦缺血損傷和大鼠彌散性不完全性全腦缺血損傷的保護(hù)作用。結(jié)果表明,雛菊葉龍膽酮可減輕大鼠腦缺血后的腦損傷程度;延長(zhǎng)小鼠斷頭后的張口喘息時(shí)間;降低大鼠腦缺血后的腦指數(shù),說(shuō)明雛菊葉龍膽酮對(duì)缺血性腦損傷具有顯著的腦保護(hù)作用。同時(shí)發(fā)現(xiàn),大鼠腦缺血后,腦內(nèi)MDA含量增加,超氧化物歧化酶(SOD)活力下降,腦內(nèi)谷氨酸(GLu)及γ-氨基丁酸(GABA)含量明顯增加。給予一定劑量雛菊葉龍膽酮后,可顯著升高大鼠腦內(nèi)SOD活力,降低MDA及Glu含量,說(shuō)明雛菊葉龍膽酮的腦保護(hù)作用有抗氧化及減輕興奮毒性損傷機(jī)制的介入。而給藥后使GABA含量顯著降低的確切機(jī)制還有待進(jìn)一步探討。
另外,張劍輝等[89]利用電凝法制作大鼠右側(cè)大腦中動(dòng)脈阻塞(MCAO)模型,證明了口服給藥雛菊葉龍膽酮能改善MCAO缺血后神經(jīng)功能障礙,并縮小腦梗塞面積,減輕相關(guān)腦區(qū)神經(jīng)元損傷程度,顯著抑制大鼠局灶性腦缺血損傷細(xì)胞間黏附分子-1(ICAM-1)表達(dá),上調(diào)缺血周邊區(qū)神經(jīng)元B淋巴細(xì)胞瘤-2(Bcl-2)抗凋亡蛋白的表達(dá)。說(shuō)明雛菊葉龍膽酮對(duì)大鼠局灶性腦缺血損傷有保護(hù)作用,其作用機(jī)制可能與抑制ICAM-1表達(dá)和促進(jìn)Bcl-2表達(dá)有關(guān)。
4.1 急性毒性
丁莉等[90]以小鼠為研究對(duì)象,經(jīng)口灌胃方式給藥,通過(guò)急性毒性實(shí)驗(yàn)證明,在實(shí)驗(yàn)期間小鼠未出現(xiàn)明顯中毒癥狀和死亡;小鼠對(duì)雛菊葉龍膽酮最大耐受量(MTD)為15 g·kg-1。表明該化合物安全可靠,可為其制劑開(kāi)發(fā)提供一定的理論依據(jù)。
4.2 遺傳毒性
文莉等[91]以0.9%氯化鈉溶液作為陰性對(duì)照,環(huán)磷酰胺作為陽(yáng)性對(duì)照,通過(guò)小鼠骨髓嗜多染紅細(xì)胞(PCE)微核實(shí)驗(yàn)證明,雛菊葉龍膽酮各組小鼠骨髓嗜多染紅細(xì)胞細(xì)胞微核發(fā)生率明顯低于陽(yáng)性對(duì)照組,且差異有統(tǒng)計(jì)學(xué)意義,而與陰性對(duì)照組比較差異無(wú)統(tǒng)計(jì)學(xué)意義,說(shuō)明雛菊葉龍膽酮對(duì)體細(xì)胞無(wú)明顯的致突變作用。另外,選用已知致突變物二氨基芴、1,8-二羥基蒽醌、敵克松、疊氮化鈉作為陽(yáng)性對(duì)照,二甲基亞砜為陰性對(duì)照,通過(guò)Ames實(shí)驗(yàn)證明,無(wú)論是否加入誘導(dǎo)劑,0.5~5000 μg·mL-1的雛菊葉龍膽酮對(duì)實(shí)驗(yàn)用4種菌株(鼠傷寒沙門(mén)菌組氨酸營(yíng)養(yǎng)缺陷型TA97、TA98、TA100、TA102)所誘發(fā)的回變菌落數(shù)均與自發(fā)回變和陰性對(duì)照相近,與超過(guò)陰性對(duì)照組的2倍才判斷為能導(dǎo)致突變的評(píng)價(jià)標(biāo)準(zhǔn)還有較大距離。
綜上所述,雛菊葉龍膽酮主要分布于龍膽科獐牙菜屬(33種)、假龍膽屬(20種)、龍膽屬(7種)植物中。此外,其在龍膽科扁蕾屬(1種)、腺鱗草屬(1種)、蘿藦科娃兒藤屬(1種)和鳶尾科鳶尾屬(1種)植物中也有少量分布。雛菊葉龍膽酮在降血糖、抗氧化、抗菌、抗病毒、抑制膽堿酯酶及單胺氧化酶、保護(hù)心血管系統(tǒng)及缺血性腦損傷等方面具有一定的療效。同時(shí)毒性研究證實(shí),該化合物安全,且沒(méi)有表現(xiàn)出明顯的致突變作用。
[1] Lesch B,Br?se S.A short,atom-economical entry to tetrahydroxanthenones[J].Angew Chem Int Ed Engl,2004,43(1):115-118.
[2] Tozhiboev M M,Botirov E K,Usmanova G A.Xanthones and flavonoids fromGentianaalgidaPall[J].Russ J Bioorg Chem,2011,37(7):866-870.
[3] Hostettmann M,Hostettmann K,Sticher O.Xanthones,flavones,and secoiridoids of AmericanGentianaspecies[J].Phytochemistry,1981,20(3):443-446.
[4] Isakovic A,Jankovic T,Harhaji L,et al.Antiglioma action of xanthones fromGentianakochiana:Mechanistic and structure-activity requirements[J].Bioorg Med Chem,2008,16(10):5683-5694.
[5] Schaufelberger D,Hostettmann K.Chemistry and pharmacology ofGentianalactea[J].Planta Med,1988,54(3):219-221.
[6] Wolfender J L,Rodriguez S,Hostettmann K,et al.Liquid chromatography/ultra violet/mass spectrometric and liquid chromatography/nuclear magnetic resonance spectroscopic analysis of crude extracts of Gentianaceae species[J].Phytochem Anal,1997,8(3):97-104.
[7] Nadinic E L,Saavedra C L,Lira P D L,et al.Tetraoxygenated xanthones fromGentianellaflorida[J].Pharm Biol,1997,35(5):379-381.
[8] Rivaille P,Raulais D.Xanthones and other constituents of grentiana and swertia.presence of a new triterpene in gentiana verna[J].Comptes Rendus des Seances de l’Academie des Sciences,Serie D:Sciences Naturelles,1969,269(12):1121-1124.
[9] Nadinic E,Penna C,Saavedra C.Isolation of antimicrobial compounds fromGentianellaachalensis(Gilg) Ho & Liu(Gentianaceae) extracts[J].Lat Am J Pharm,2002,21(2):123-130.
[10] Lv L J,Li M H.Terpenoids,flavonoids and xanthones fromGentianellaacuta(Gentianaceae)[J].Biochem Syst Ecol,2009,37(4):497-500.
[11] Jankovic T,Krstic D,Aljancic I,et al.Xanthones and C-glucosides from the aerial parts of four species ofGentianellafrom Serbia and Montenegro[J].Biochem Syst Ecol,2005,33(7):729-735.
[12] Urbain A,Marston A,Grilo L S,et al.Xanthones fromGentianellaamarellassp.acuta with acetylcholinesterase and monoamine oxidase inhibitory activities[J].J Nat Prod,2008,71(5):895-897.
[13] Benn M H,Joyce N I,Lorimer S D,et al.Xanthones and bisxanthones in five New Zealand and subantarctic Gentianella species[J].Biochem Syst Ecol,2009,37(4):531-534.
[14] Zhang Y J,Yang C R.Chemical studies onGentianellaazurea,a Tibetan medicinal plant[J].Acta Bot Yunnan,1994,16(4):401-406.
[15] Markham R.Gentian pigments.II.Xanthones fromGentianabellidifolia[J].Tetrahedron,1965,21(6):1449-1452.
[16] Urbain A,Marston A,Marsden-Edwards E,et al.Ultra-performance liquid chromatography/time-of-flight mass spectrometry as a chemotaxonomic tool for the analysis of Gentianaceae species[J].Phytochem Anal,2009,20(2):134-138.
[17] Rosella M A,Etile E D,Spegazzini S L,et al.97-Parametros micrograficosy fitoquimicos para el reconocimiento de dos especies de Gentianella(Gentianaceae)[J].Bol Latinoam Caribe Plant Med Aromát,2007,6(6):384-385.
[18] Báez D H,Quintero M,Nieves B.Toxicity,antimicrobial activity and detection of xanthones inGentianellanevadensis[J].Ciencia,1999,7(2):111-117.
[19] Hostettmann-Kaldas M,Jacot-Guillarmod A.Contribution to the phytochemistry of the genus Gentiana.Part XXIII.Xanthones and flavone C-glucosides of the genus Gentiana(subgenus Gentianella)[J].Phytochemistry,1978,17(12):2083-2086.
[20] Massias M,Carbonnier J,Molho D.Chemotaxonomy of Gentianopsis:Xanthones,C-glycosylflavonoids and carbohydrates[J].Biochem Syst and Ecol,1982,10(4):319-327.
[21] Tomas G E,Lock O,Jurupe H.Chemical study and hypoglycemic and hypolipemic activity ofGentianellathyrsoideaHooker Fabris[J].Boletin de la Sociedad Quimica del Peru,1999,65(4):231-238.
[22] KhanT A,HaqqanM H,NisarN M.Chemical investigation ofSwertiaalata[J].Planta Med,1979,37(2):180-181.
[23] 楊俊美.固公果根和美麗獐牙菜的化學(xué)成分研究[D].昆明:云南中醫(yī)學(xué)院,2014.
[24] 李兆云,王聰,張楨,等.賓川獐牙菜化學(xué)成分研究[J].時(shí)珍國(guó)醫(yī)國(guó)藥,2011,22(5):1086-1087.
[25] 田巒鳶,陳家春,黃風(fēng)嬌,等.高效液相法同時(shí)測(cè)定獐牙菜屬植物中四種活性成分(英文)[J].中國(guó)天然藥物,2008,6(6):444-449.
[26] Ya B Q,Gen X P.Four xanthones fromSwertiacalycinaFranch[J].Pharm Pharmacol Commun,1998,4(12):595-596.
[27] Shi G F,Wang G Y,Chen X F.Screening of radical-scavengine natural neuroprotective antioxidants fromSwertiachirayita[J].Acta Biol Hun,2013,64(3):267-278.
[28] Saeed M A,Khan Z U D,F(xiàn)ord M R.Antimicrobial potential of some xanthones fromSwertiaciliataBuch et Ham[J].Acta Pharm Turcica,1998,40(4):175-184.
[29] 徐康平,申健,李福雙,等.多波長(zhǎng)HPLC同時(shí)測(cè)定3種獐牙菜屬植物中6種活性成分[J].中國(guó)中藥雜志,2009,34(11):1384-1389.
[30] Tomimori T,Yoshizaki M,Namba T.Nepalese crude drugs.II.Xanthone constituents of the plants of Swertia species[J].Yakugaku Zasshi,1974,94(5):647-651.
[31] 肖晶.北方獐牙菜的化學(xué)成分研究[D].大連:大連理工大學(xué),2010.
[32] Hu B L,Hong S F,ShuH F,et al.The xanthones ofSwertiaerythrostictaMaxim[J].Acta Bot Sin,1992,34(11):886-886.
[33] Liu Y,Xu Q,Xue X,et al.Two-dimensional LC-MS analysis of components inSwertiafranchetianaSmith[J].J Sep Sci,2008,31(6/7):935-944.
[34] Wang H L,Cao T W,Jiang F Q,et al.Swerpunilactones A and B,the first example of xanthone and secoiridoid heterodimers fromSwertiapunicea,S.hispidicalyx,andS.yunnanensis[J].Tetrahedron Lett,2013,54(21):2710-2712.
[35] Ghosal S,Biswas K,Jaiswal D K.Chemical constituents of Gentianaceae.Part 27.Xanthone and flavonol constituents ofSwertiahookeri[J].Phytochemistry,1980,19(1):123-126.
[36] Denisova A,Solov’eva V,Glyzin I,et al.Xanthone glycosides from the aboveground part ofSwertiaiberica[J].Khim Prir Soedin,1980(5):724-5
[37] Wang Z,Ma C,Tang S,et al.Qualitative and quantitative analysis of Swertia herbs by high performance liquid chromatography-diode array detector-mass spectrometry(HPLC-DAD-MS)[J].Chem Pharm Bull,2008,56(4):485-490.
[38] 周青.貴州獐牙菜化學(xué)成分研究[D].武漢:湖北中醫(yī)學(xué)院,2003.
[39] Zhou H M,Liu Y L,Blasko G,et al.Swertia bisxanthone-I fromSwertiamacrosperma[J].Phytochemitry,2008,28(12):3569-3571.
[40] Fan G,Luo W Z,Luo S H,et al.Metabolic discrimination ofSwertiamussotiiandSwertiachirayitaknown as “Zangyinche” in traditional Tibetan medicine by 1H NMR-based metabolomics[J].J Pharm Biomed Anal,2014,98:364-370.
[41] 郭志威.顯脈獐牙菜活性成分及其含量測(cè)定[D].長(zhǎng)沙:中南大學(xué),2007.
[42] Prakash A,Basumatary P C,Ghosal S,et al.Chemical constituents ofSwertiapaniculata[J].Planta Med,1982,45(5):61-62.
[43] Hostettmann K,Jacot-Guillarmod A.Identification of xanthones and new arabinosides of flavone C-glucosides fromSwertiaperennisL[J].Helv Chim Acta,1976,59(5):1584-1591.
[44] Baslas R K,Kumar P.Isolation and characterization of biflavanone and xanthones in the fruits ofGarciniaxanthochymus[J].Acta Cienc Indica Chem,1981,7(1/4):31-34.
[45] Li J C,F(xiàn)eng L,Sun B H,et al.Hepatoprotective activity of the constituents inSwertiapseudochinensis[J].Biol Pharm Bull,2005,28(3):534-537.
[46] Menkovic N,Savikin-Fodulovic K,Bulatovic V,et al.Xanthones fromSwertiapunctate[J].Phytochemistry,2002,61(4):415-420.
[47] Zheng X Y,Yang Y F,Li W,et al.Two xanthones fromSwertiapuniceawith hepatoprotective activities in vitro and in vivo[J].J Ethnopharmacol,2014,153(3):854-863.
[48] Ghosal S,Sharma P V,Chaudhuri R K,et al.Chemical constituents of gentianaceae.XIV.Tetraoxygenated and pentaoxygenated xanthones ofSwertiapurpurascens[J].J Pharm Sci-US,1975,64(1):80-83.
[49] Hirakawa K,Yoshida M,Nagatsu A,et al.Chemopreventive action of xanthone derivatives on photosensitized DNA damage[J].Photochem Photobiol,2005,81(2):314-319.
[50] 廖志新,胡伯林,紀(jì)蘭菊.輪葉獐牙菜的化學(xué)成分研究[J].植物學(xué)報(bào),1991,33(12):968-970.
[51] 于瑩,王世盛,丁鳳娟,等.云南獐牙菜化學(xué)成分的分離與鑒定[J].中國(guó)藥物化學(xué)雜志,2010,20(2):125-128.
[52] 羅洲飛,劉妮娜,徐彥軍,等.扁蕾不同部位的化學(xué)成分研究[J].湖南農(nóng)業(yè)科學(xué),2012(9):99-102.
[53] Olennikov D N.Chemical investigation ofAnagallidiumdichotomumand anticholinesterase activity of its constituents[J].Chem Nat Compd,2014,49(6):1137-1139.
[54] Suleiman K,Hideki T,Munekazu I.A xanthone C-glycoside fromIrisnigricans[J].Phytochemistry,1995,38(3):729-731.
[55] Yao S,Tang C P,Ye Y.Secoiridoids and xanthones fromTylophorasecamonoidesTsiang[J].J Asian Nat Prod Res,2008,10(5/6):591-596.
[57] 劉東鋒,楊成東.一種雛菊葉龍膽酮的制備方法:CN103275054A[P].2013-09-04.
[58] Shi G F,Lu R H,Yang Y S.Isolation and crystal structure of xanthones fromSwertiaChirayita[J].Chin J Struc Chem,2004,23(10):1164-1168.
[59] 范剛.基于1H-NMR代謝物組學(xué)技術(shù)的多基源中藏藥品種質(zhì)量評(píng)價(jià)研究[D].成都:成都中醫(yī)藥大學(xué),2012.
[60] 萬(wàn)落生.貴州獐牙菜抗糖尿病活性和物質(zhì)基礎(chǔ)研究[D].武漢:華中科技大學(xué),2013.
[61] Basnet P,Kadota S,Shimizu M,et al.Bellidifolin:a potent hypoglycemic agent in streptozotocin(STZ)-induced diabetic rats fromSwertiajaponica[J].Planta Med,1994,60(6):507-511.
[62] Basnet P,Kadota S,Shimizu M,et al.Bellidifolin stimulates glucose uptake in rat 1 fibroblasts and ameliorates hyperglycemia in streptozotocin(STZ)-induced diabetic rats[J].Planta Med,1995,61(5):402-405.
[63] Yamakaral M,Matsuda H.Antieholinergieaetion ofSwertiajaponieaand anaetiveeon stituent[J].J Ethnopharmacol,1991,33(1):31-35.
[64] Tian L Y,Bai X,Chen X H,et al.Anti-diabetic effect of methylswertianin and bellidifolin fromSwertiapuniceaHemsl.and its potential mechanism[J].Phytomedicine,2010,17(7):533-539.
[65] Satendra S,Asthana R K,Gupta R C.Assessment of systemic interaction betweenSwertiachirataextract and its bioactive constituents in rabbits[J].Phytother Res,2009,23(7):1036-1038.
[66] 文莉.紫紅獐牙菜和湖北麥冬降血糖活性及遺傳毒性研究[D].武漢:湖北中醫(yī)學(xué)院,2008.
[67] 王世盛.藏茵陳活性組分的制備分離和化學(xué)表征[D].大連:中國(guó)科學(xué)院大連化學(xué)物理研究所,2004.
[68] 張媛嬡.藏藥大籽獐牙菜化學(xué)成分及生物活性研究[D].成都:西南交通大學(xué),2006.
[69] Ashida S,Noguchi S F,Suzuki T.Antioxidative components,xanthone derivatives,inSwertiajaponicaMakino[J].J Am Oil Chem Soc,1994,71(10):1095-1099.
[70] Rana V S,Rawat M S M.A new xanthone glycoside and antioxidant constituents from the rhizomes of Swertia speciose[J].Chem Biodivers,2005,2(10):1310-1315.
[72] 張秀橋.復(fù)方紫金肝泰抗HBV物質(zhì)基礎(chǔ)的研究[D].武漢:湖北中醫(yī)學(xué)院,2006.
[73] 黃鳳嬌.紫紅獐牙菜化學(xué)成分的含量測(cè)定及體外抗HBV活性物質(zhì)的篩選[D].武漢:湖北中醫(yī)學(xué)院,2006.
[74] Cao T W,Geng C A,Ma Y B,et al.Xanthones with anti-hepatitis B virus activity fromSwertiamussotii[J].Planta Med,2013,79(8):697-700.
[76] Koji H,Li J X,Basnet P,et al.Hepatoprotective principles ofSwertiajaponicaMakino on D-galactosamine/lipopolysaccharide-induced liver injury in mice[J].Chem Pharm Bull,1997,45(11):1823-1827.
[77] Koji H,Kadota T,Basnet P,et al.Tetrahydroswertianolin:a potent hepatoprotective agent fromSwertiajaponicaMakino[J].Chem Pharm Bull,1997,45(3):567-569.
[78] 潘錫平,林艷和,李彪.一種治療肝炎和糖尿病的藥物組合物:CN1686141[P].2005-10-26.
[79] Urbain A,Marston A,F(xiàn)ererira Q E,et al.Xanthones fromGentianacampestrisas new acetylcholinesterase inhibitors[J].Planta Med,2004,70(10):1011-1014.
[80] Masand V H,Patil K N,Mahajan D T,et al.3D-QSAR studies on xanthone derivatives to understand pharmacological activities as MAO inhibitors[J].Pharma Chemica,2010,2(5):22-32.
[81] Masand V H,Patil K N,Mahajan D T,et al.3D-QSAR studies on xanthone derivatives to understand pharmacological activities as MAO inhibitors[J].Pharma Chemica,2010,2(4):298-308.
[82] Deeb O,Alfalah S,Clare B W.QSAR of aromatic substances:MAO inhibitory activity of xanthone derivatives[J].J Enzym Inhib Med Ch,2007,22(3):277-286.
[83] Nunez M B,Maguna F P,Okulik N B,et al.QSAR modeling of the MAO inhibitory activity of xanthones derivatives[J].Bioorg Med Chem Lett,2004,14(22):5611-5617.
[84] Fowler C J,Ross S B.Selective inhibitors of monoamine oxidase A and B:biochemical,pharmacological,and clinical properties[J].Med Res Rev,1984,4(3):323-58.
[85] Ohishi N,Suzuki T,Ogasawara T,et al.Xanthone derivatives as inhibitors for monoamine oxidase[J].J Mol Catal B-Enzym,2000,10(1/3):291-294.
[86] 武海軍,李旻輝,張海濤,等.Bellidifolin對(duì)麻醉大鼠心電圖的影響[J].包頭醫(yī)學(xué)院學(xué)報(bào),2011,27(1):22.
[88] 宋慧君,張建輝,閆平,等.雛菊葉龍膽酮對(duì)缺血性腦損傷保護(hù)作用的實(shí)驗(yàn)研究[J].大連醫(yī)科大學(xué)學(xué)報(bào),2007,29(2):110-112.
[89] 張建輝,宋慧君,李淑媛.雛菊葉龍膽酮對(duì)局灶性腦缺血損傷的保護(hù)作用及機(jī)制探討[J].中國(guó)藥理學(xué)通報(bào),2005,21(2):220-224.
[90] 丁莉,文莉,汪暉,等.Bellidifolin對(duì)小鼠的急性毒性及對(duì)小鼠骨髓細(xì)胞的微核效應(yīng)[J].內(nèi)科,2006,1(2):145-146.
[91] 文莉,陳家春.降血糖活性成分Bellidifolin遺傳毒性研究[J].醫(yī)藥導(dǎo)報(bào),2008,27(11):1317-1319.
ResearchProgressonBellidifolin
ZHAO Wei1,HANHuarui2,ZHAOYachan1,SHANGZhiqiang1,LYULijuan1
(1.DepartmentofBasicScience,TianjinAgriculturalUniversity,Tianjin300384,China;2.BaotouMedicalCollege,Baotou,InnerMongolia014060,China)
Bellidifolin,a kinds of natural tetraoxygenated xanthone,was mainly distributed among genusSwertia,Gentianella,andGentianain family Gentianaceae and possesses multifarious pharmacological activities,including hypoglycemic,anti-oxidant,anti-bacterial,anti-viral,protecting cardiovascular and cerebral is chemia injuries,etc.In order to provide scientific references for the in-depth study,development and utilization of the compound,this review comprehensively summarizes the distribution,preparation,quality evaluation,pharmacological activities and toxicity studies of bellidifolin.
Bellidifolin;distribution;pharmacological activities;progress
2015-04-25)
國(guó)家自然科學(xué)基金項(xiàng)目(81303306,81160504);天津市應(yīng)用基礎(chǔ)與前沿技術(shù)研究計(jì)劃(15JCQNJC13400);天津市大學(xué)生創(chuàng)新創(chuàng)業(yè)訓(xùn)練計(jì)劃項(xiàng)目(201410061052,201410061159)
*
尚志強(qiáng),博士,講師,研究方向:藥物合成化學(xué),E-mail:shangzq1978@sina.com;呂麗娟,博士,講師,研究方向:藥物分析與晶型藥物研究,E-mail:lv_lijuan@aliyun.com
10.13313/j.issn.1673-4890.2016.5.029