桔梗中三萜皂苷类化学成分研究进展

1、基金项目:国家自然科学基金资助项目(30772728作者简介:郭文杰,男,硕士研究生*通讯作者:许旭东,男,副研究员,博士 Te:l (01062890291 E-m ai:l xdxui m p l ad 1ac 1cn #综 述#桔梗中三萜皂苷类化学成分研究进展郭文杰,许旭东*,魏建和,杨峻山(中国医学科学院-中国协和医科大学药用植物研究所,北京100094摘要:目的 为深入研究和开发利用桔梗提供科学依据,并对其研究开发前景进行探讨。方法 通过查阅近10年来关于桔梗研究的文献,对桔梗主要活性成分桔梗皂苷的化学结构、药理活性进行了系统的总结。结果 目前已知桔梗中皂苷类成分共有40多种,桔梗皂

2、苷具有抗炎、保肝、抗癌、降血糖等药理活性。结论 桔梗作为一种药食两用的植物,具有广阔的开发应用前景。关键词:桔梗;三萜皂苷;药理活性中图分类号:R 28411 文献标识码:A 文章编号:1001-2494(200811-0801-04 桔梗为桔梗科多年生植物桔梗P l atycodon grand i f l oru m (Jacp 1A 1DC 1的干燥根,又名四叶菜、土人参、苦梗菜等。广泛分布于我国、朝鲜半岛和日本;在我国东北和华北地区,桔梗被广泛种植,资源丰富。桔梗性微温,味苦、辛、平,归肺经,有开宣肺气,祛痰排脓之功效,常用于外感咳嗽、咳痰不清、咽喉肿痛、胸闷腹胀、痢疾腹痛、血淤水肿、

3、癃闭等症,系常用中药1-3;桔梗又是一种很好的保健和功能食品。现将近10年来桔梗的三萜皂苷类化学成分、药理学等方面的研究进展进行总结,为深入研究和开发利用桔梗提供科学依据。1 三萜皂苷类化学成分研究自20世纪50年代起,各国学者对桔梗中的化学成分进行了系统的研究。发现其主要的生物活性成分为三萜皂苷,目前从桔梗中共分离得到了45个三萜皂苷类化学成分(表1,根据桔梗三萜皂苷的苷元类型分为远志酸(po l yga l ac ic aci d类;桔梗皂苷元(platycodi g en i n衍生物,也称为桔梗酸(p latycod i c ac i d类和桔梗二酸(platycodi g en i

4、c acid衍生物3种结构类型4,其糖基多连在C3或C28。桔梗皂苷元母核的化学结构见图1 。图1 桔梗皂苷元母核的化学结构F i g 11 Structure o f platycod i genin此外,桔梗中还含大量的多糖以及甾体(A -菠菜甾、v 7-豆甾烯醇、B -谷甾醇等,脂肪油、脂肪酸、氨基酸、蛋白质、生物碱、挥发油等化学成分1,23-25。2 三萜皂苷的药理学研究现代药理学研究表明,桔梗的三萜皂苷类化学成分具有抗炎、祛痰、保肝、降血糖、抑制脂肪吸收、抗氧化、抗菌、抗肿瘤等广泛的药理作用26。211 抗炎止痛作用桔梗皂苷能够抑制前列腺素E 通路和拮抗LPS 诱导的小鼠腹膜巨噬细胞

5、(M NO 生成量增加,从而对各种炎症显示有较强的抗炎作用27。结果显示,桔梗皂苷浓度为10mm o l #L -1和30mm o l #L -1时,能抑制大鼠促癌物12-O -十四烷酰佛波醇-13-乙酯(TPA 诱导的腹腔巨噬细胞中PG E 2产生28。212 祛痰作用桔梗有促进支气管黏膜分泌从而有祛痰的作用29。体外药理学研究表明,桔梗皂苷D 和桔梗皂苷D 3均能增加SD 大鼠气管上皮金黄仓鼠细胞(RTSE 细胞黏蛋白的分泌。体外实验中,桔梗皂苷D 和桔梗皂苷D 3的质量浓度为200m g #L -1时S D 大鼠气管上皮细胞(rat tracheat surpace ep ithe -l

6、i a l cells ,RT SE 细胞黏蛋白的分泌分别增加25217%和37012%;在体内实验中,20mg #L -1的桔梗皂苷D 3对大鼠黏蛋白释放的增加作用比质量浓度均为200m g #L -1的ATP 和氨溴索的作用更强27。213 保肝作用桔梗皂苷类成分具有抗肝纤维化,抗肝脂质过氧化,保护肝细胞,促进肝脏的物质和能量代谢加速肝损伤恢复,改善肝脏微循环,抑制肝肿瘤细胞等作用30。桔梗中皂苷类成分能抑制四氯化碳诱导的肝毒性和其所导致的肝炎和肝部肿大,试验发现,喂食桔梗皂苷100m g #kg -1的小鼠其血清中丙氨酸转氨酶(ALT 和天门冬酸氨基转移酶(AST 是表1桔梗中三萜皂苷成

7、分Tab11Saponi ns i n P lat y codon grandifloru m(Jacp1A1DC1No1N a m e CatSub1R2R6R7Re f11P l a t ycodi n D A G l u H A ra2-1Rha4-1Xy l3-1Ap i5 2P l a t ycodi n A A G l u Ara2-1Rha(2-OA c4-1Xy l3-1A pi H6 3P l a t ycodi n B A G l u Ara2-1Rha(3-OA c4-1Xy l3-1A pi H6 4Deapi o-pl a t ycodi n D A G l u Ar

8、a2-1Rha4-1Xyl H7 5P l a t ycodi n D2A Am i Ara2-1Rha4-1Xyl3-1Api H8 62d-O-acet y l pl atycodi n D2A Am i Ara2-1Rha(2-OA c4-1Xy l3-1A pi H8 73d-O-acet y l pl atycodi n D2A Am i Ara2-1Rha(3-OA c4-1Xy l3-1A pi H8 8P l a t ycodi n D3A Gen Ara2-1Rha4-1Xyl3-1Api H9 9Deapi o-pl a t ycodi n D3A Gen Ara2-1Rh

9、a4-1Xyl H7 10P l a t ycodi n E A Gen6-1G lc Ara2-1Rha4-1Xyl3-1Api H10 11P l a t ycodi n G1A Gen6-1G lc Ara2-1Rha4-1Xyl H10 12P l a t ycodi n G2A Gen6-1G lc Ara2-1Rha4-1Xyl H10 133-O-B-D-g l ucopyranosyl pl a t ycodi g e ni n m e t hy l ester A G l u C H3H11 143-O-B-D-l a m i n ari bi osy l pl a t yc

10、ogeni n m e t hy l ester A Am i C H3H11 153-O-B-D-genti obi osy l plat ycodi g e n i n m e t hy l ester A Gen C H3H11 16P l a t ycogenic ac i d A B H H H12 17P l a t ycogenic ac i d B C H H OH12 18M e t hy-l p l at y coge nate A D G l u Ara2-1Rha4-1Xyl3-1Api H13 19M e t hy-l2-O-m ethy l plat y c og

11、e nate A E G l u Ara2-1Rha4-1Xyl3-1Api H13 20D i m ethy-l3-O-B-D-g l u copy ra nosy l pl atycogena t e A D G l u C H3H1421D i m e t hy-l2-O-m e t hy-l3-O-B-D-g l ucopy ra nosy l plat y c og e nate A E G l u C H3H1422P l a t yconic ac i d A lact one J G l u Ara2-1Rha4-1Xyl3-1Api-15 23D-gl ucopy ra no

12、sy l pl atycogeni n A lacto ne m e t hy l ester J G l u C H3-15 24P ol yga l ac i n D G G l u Ara2-1Rha4-1Xyl3-1Api H16 252d-O-acet y l po l yga l ac i n D G G l u Ara2-1Rha(2-OA c4-1Xy l3-1A pi H16 263d-O-acet y l ace t y l pygalaci n D G G l u Ara2-1Rha(3-OA c4-1Xy l3-1A pi H16 27P ol yga l ac i n

13、 D2G Am i Ara2-1Rha4-1Xyl3-1Api H16 282d-O-aeet y l po l yga l ae i n D2G Am i Ara2-1Rha(2-OA c4-1Xy l3-1A pi H16 293d-O-aeet y l po l yga l ae i n D2G Am i Ara2-1Rha4-1Xyl H16 30P l a t ycos i de A G G l u C H3H17 31P l a t ycos i de B G Am i Ara2-1Rha(3-OA c4-1Xy l H17 32P l a t ycos i de C G Gen

14、Ara2-1Rha4-1Xyl3-1Api H18 33P l a t ycos i de D G G l u Ara2-1Rha(2-OA c4-1Xy l H18 34P l a t ycos i de G3G G l u Ara2-1Rha4-1Xyl3-1Api H18 35M e t hy-l3-O-B-D-g l ueopy ra nosy l po l yga l aeate G G l u C H3H18 36M e t hy-l3-O-B-l a m i nari bi osyl po l yga l aea t e G Gen C H3H10 37P l a t ycoge

15、nic-ac i d C H H H OH13 38P l a t ycodi n H G Gen Ara2-1Rha4-1Xyl H19 39P l a t ycodi n I G G l c6-1G l c6-1G lc Ara2-1Rha4-1Xyl H19 40P l a t ycodi n J G G l u Ara2-1Rha4-1Xyl H19 41P l a t ycodi n K A Am i H H19 42P l a t ycodi n L A Gen H H19 43Deapi o-pl a t ycodi n E A Gen6-1G l u Ara2-1Rha(2-O

16、A c4-1Xy l H20 44P l a t ycodi n F I G l u Ara2-1Rha H21 4516-Oxo-p l at y co d i n D F G l u-P ra n Api1-3Xyl1-4Rha1-2Ara H22未喂食桔梗皂苷小鼠血清中的011倍;同时桔梗总皂苷还能抑制a l pha-肌动蛋白(al pha-S M A的上升31;桔梗总皂苷能阻断肝药酶对乙酰氨基酚的生物激活从而起到保护对乙酰氨基酚引起的肝损伤的作用32。214降血糖作用桔梗能够明显降低肥胖型和瘦型的Zucker大鼠的血浆中的甘油三酸酯的浓度,桔梗还能够降低胆固醇和增加血浆中胰岛素的含量;

17、并能够降低餐后葡萄糖的含量。桔梗可以使喂食4周后肥胖Zucker大鼠血浆中的葡萄糖的转运蛋白4 (G LUT4的蛋白水平有明显的上升33。215对脂肪代谢的研究桔梗水提取物能抑制三油酸甘油酯与卵磷脂混合形成的乳胶微粒分解34。桔梗总皂苷具有抑制胰脂肪酶活性,减少对食物中脂肪的吸收,从而减轻肥胖35。桔梗能显著降低高脂血症大鼠血清和肝脏脂肪浓度,显著降低血清和肝脏中总胆固醇和甘油三酯的浓度,降低低密度脂蛋白(LDL和升高高密度脂蛋白(HDL的浓度,同时桔梗组的动脉硬化指标也较模型组低36。桔梗总皂苷可使胰脂肪酶的活性抑制在4117%水平以下;桔梗皂苷D、桔梗皂苷A、桔梗皂苷C可使其活性分别抑制在

18、3148%,313%,512%水平37。大剂量(200 mg#kg-1#d-1的桔梗总皂苷对胰脂肪酶的降低作用极其显著(P<0101,远超过阳性药物绞股蓝的作用(P<0105,并且对其余的HDL-C,LDL-C等次要因素的影响也在阳性药物之上,这主要是由于桔梗总皂苷含有各种降脂作用的苷元从而对外源性胆固醇具有很强的清除作用38。216对中枢神经系统的作用桔梗皂苷D在011L g#g-1的剂量下腹腔内、脑室内和鞘内注射对小鼠甩尾、扭体和福尔马林实验有剂量依赖性的抗伤害性感受作用。同时研究还得出桔梗皂苷D作用于神经中枢,与去甲肾上腺素和5-羟色胺下行通路有关39。217抗氧化作用桔梗总

19、皂苷可以抑制酪氨酸酶的活性,在质量浓度为1g#L-1时,总皂苷抑制率达388%,其中桔梗皂苷D抑制酪氨酸酶的活性最强,在质量浓度为1g#L-1时,其抑制率达56217%40。218抗菌的协同作用桔梗单味药无抗菌作用,甘草单味药抗菌活性较差,桔梗与甘草配伍,其具有显著的抑菌作用,复方水提取液达到一定的浓度时,还具有杀菌的作用。其抗菌作用的机制还有待进一步的深入研究41。219抗肿瘤作用桔梗皂苷中去芹菜糖桔梗皂苷E具有抑制S K-OV-3, A549、S K-M EL-2等肿瘤细胞增殖的作用20。此外,桔梗三萜皂苷类化学成分还具有镇咳、抗溃疡、降血压、扩张血管、解热镇痛、镇静、抗胆碱、促进胆酸分泌

20、等药理作用26。3展望桔梗作为一种药食两用的植物,资源丰富,三萜皂苷类为其主要化学成分,生物活性多样,几无毒副作用,在临床上具有广泛用途和良好疗效,是一种很具开发潜力的常用中药。近年来,随着对桔梗研究的深入,新的三萜皂苷类化合物不断被发现,并发现其有显著的抗癌活性。因此,桔梗在新药和开发保健食品两个方面均具有很好的开发前景。但目前对桔梗的药理活性研究尚不够深入,更缺乏在生物活性研究的指导下对其活性成分的研究,所以有必要对桔梗在药理学、天然药物化学和保健食品等方面进行深入系统的研究,确定桔梗的生物活性的物质基础,为桔梗的可持续开发和利用提供科学依据。REFERENCES1GAO W Y,L I

21、Z L1Proceed i ng of m odern res earc h on P latycodongrandi f l orum A1DCJ.P ri m J Ch i n M a tM e d(基层中药杂志,1996,10(2:48-49.2M AO Y L.C li n i cal val ue of P lat ycodon grandi f l orum A.DCJ.Ch i na Pharm(中国药业,2001,10(10:65.3DI NG Y Q.Eff ect and app li cati on of P lat ycodon grandiflorum A.DCJ.C

22、h i na J Ch i n M a te r M e d(中国中药杂志,1998,23(5:308-309.4H E M L,C H ENG XW,CHEN J K,et a l.The sapon i ns i n P l a t yc-odon grand i florum A.DC and t heir anal ysisJ.T rad it Chin DrugR es C lin Phar m acol(中药新药与临床药理,2005,16(6:457-459.5TADA A,KANE I W A Y,SHOJI J,e t al.S t ud i es on the sapon i

23、 ns ofthe roots of P latycodon grandiflorum A.DCJ.Che m P ha r mBu ll,1975,23(11:2965-2972.6KONISH I T,TADA A,S HO JI J,et al.The struct u res of p l at ycod-i n A and C m onoacetylated s apon i n s of t he roots of P la t yc odongrandi f l orum A.DCJ.Che m Phar m B ull,1978,26(1:668-670.7IS H II H,

24、TORI K,TOZ YO T,et a l.S truct ures of platycod i n D3platycon i c acid A,and t h ei r derivati ves,sapon i ns i solated fro mroots of P l a t yc odon g rand i florum A.DC deter m i ned by carbon-13N M R s pectroscopyJ.Che m L e tt,1978,26(2:719-722.8ISH II H,TORI K,TOZYO T,e t al.S truct u res of p

25、ol ygalaci n D andD2,p l atycod i n D and D2and thei r m onacetates s apon i n s i solatedfro m P l a t yc odon grandifl orum A.DC det er m i n ed by carbon-13nu-cl ear m agneti c res onan ce s pectroscopyJ.Ch e m P har m Bu ll,1978,26(2:674-677.9WANG C H,GEORGI A B,SCHULLER L,et al.Plat ycod i n D

26、andD3is o l ated fro m the root of P l a t yc od on grandflorum modu late theproducti on of n itric ox i de and secreti on ofTNF-A i n acti vated RAW264.7cellsJ.Inter Immunopharm,2004,(4:1039-1049. 10NI KA I DO T,KOI KE K,M I TSUNAGA K,et al.Two ne w trit erpe-no i d sapon i ns fro m P l a t ycodon

27、grand i florumJ.Ch e m P har mB ull,1999,47(6:903-904.11HE Z D,Q I AO C F,HAN Q B,et al.N e w triterp e no i d sapon i nsfro m the roots of P l a t yco d on g randflorumJ.Tetrahe d ron,2005,61(8:2211-22l5.12AKI YAMA T,TANAKA O,S H I BATA S.Ch e m ical st ud i es on t he o-grandi f l orum A.DCJ.Che m

28、 Phar m Bu ll,1972,20(9:1957-1961.13KUBOTA T,K I TATAN I H,H I NO H H.S truct ure of p l at ycogenicaci d s A,B and C f urther triterpenoi d constit uen ts of P la t yc odongrandi f l orumJ.Ch e m S oc D,1969,22(22:1313-1314. 14IS H II H,TORI K,TOZYO T,e t al.S truct ures of prosapogen i nsfro m roo

29、ts of P latycodon g rand i florum det er m i n ed by carbon-13andhydrogen-1nuclear m agnetic resonance spectroscopyJ.Che mP harm B ull,1978,26(1:671-673.15IS H II H,TOR IK,TOZYO T,et al.Sapon i n s fro m roots of P l a t yc-odon grandflorum A.DC part2i sol ati on and struct u re of ne w triter-pene

30、gl ycos i desJ.J Che m Soc P erki n TransÑ,1984,10:66-l668.16IS H II H,TOR IK,TOZYO T,et al.Sapon i n s fro m roots of P l a t yc-odon g rand i floru m part1stru ct u re of pros apogen i nsJ.J Che mSoc P erki n Tran sÑ,1981,719:1928-1933.17AK I YA M A T,TANAKA O,SH IBATA S.Che m i cal st u

31、d i es on theoriental p l an t drugs.X X X.Sapogen i n s of t he roots of P la t yc odongrandi f l orum A.DC(1is olati on of the s apogen i ns and the st ero-che m istry of pol ygalaci c aci dJ.Che m P har m Bu ll,1972,20(9:1945-1951.18N I KA I DO T,KO I KE K,M I TSUNAGA K,et al.Triterpe no i d s ap

32、-on i ns fro m root of P l a t yc od on g rand i floru mJ.Na tM e d,1998,52(1:54-59.19FU W W,SH I M I ZU N,DOU D Q,e t a l.F i ve ne w triterp enoi dsapon i n s fro m t he roots of P latyc od on g randifl orumJ.Che mP har m Bu ll,2006,54(4:557-560.20K I M Y S,KI M J S,CHO I S U,et a l.Isolati on of

33、a ne w sapon i nand cytot oxic effect of sapon i n s fro m t h e root of P l a t yco d on grand i-fl orum on hu m an t um or cell li n esJ.P l an t a M e d,2005,71(6:566-568.21YANG X W,LI U M Y,Y Q,et al.M ethod of prepari ng prosapo-gen i n s of P ta t yc od on grand i florumJ.J J ili n Ag ric Univ

34、(吉林农业大学学报,2002,24(1:64-65.22LI W,XI ANG L,Z HANG J,et a l.A ne w triterp enoi d sapon i nfrom the roots of P l a t ycodon g rand i florumJ.Chin Che m L ett(中国化学快报,2007,18(3:306-308.23YOON Y D,HAN S B,KANG J S,et al.Tol-l li k e receptor4-de-pendent acti vati on ofm acroph ages by po l ys acchari de

35、is o l ated fro mthe rad i x of P la t yco d on g rand i florumJ.Int I mm unopha r m,2003,3(13-14:1873-1882.24DI NG C J ,W E IY D,AN Z Y ,e t al .Anal ys i s of che m i cal con -sti tuen t s of vol atil e oil fro m P latycod on grand i florum J .J N or -man B ethun e Un i v M ed Sci (白求恩医科大学学报,1996,

36、22(5:471-472.25 JI C.H ealt h p roducts P l a t yco d on g rand i florum J.ChinaH e a lt h F ood (中国保健食品,2005,10(1:6-7.26Z H ENG H Z ,DONG Z H,SE J .M odern Ch inese M e d ici n e R e -se arc h and Appli ca ti on (中药现代研究与应用(4M .B e-i ji ng :A cade m y Press ,1998:3627.27 SONG Y ,Q IY .Phar macol og

37、i cal progress on P l a t ycodon grandifl o -rum J.Ch i na Phar m (中国药房,2006,179(2:140-141.28K I M Y P ,LEE E B,K I M S Y ,e t al .Inh i b iti on of prostagland i n E 2p roduction by p latycod i n D is olated fro m t he root of P l a t ycodon grand i florum J.P l an t a M e d ,2001,67(4:362-364.29GE

38、 J F ,LI J ,YAO H W.Proceeding of t he study on t he i m m uno -logic pat hogenesis of chron i c bronch itisJ.Anhu iM e d P har m J (安徽医药,2003,7(3:163-165.30SH I N C Y,LEE W J ,LEE E B,et a l .P l at ycodin D and D 3i n -creas e ai rway mu ci n releade i n vivo in v itro rats and h a m stersJ.P lant

39、a M e d ,2002,68(3:221-225.31LEE K J ,KI M J Y,J UNG K S ,et a l .Protective effects of P l a t y -codon grand i florum on the p rogress of carbon tetrach l ori de -i ndu ced hepat otox i cit yJ .Food Ch e m Toxicol ,2004,27(12:1238-1244.32LEE K J ,YOU H J ,PARK S J ,et al .H epatop rotecti ve eff e

40、ct s of P latyc od on g rand i f l orum on aceta m i nophen -i nduced li ver da m age i n m i ceJ.Can c er L ett ,2001,174(1:73-81.33K I M K S ,SEO E K,LEE Y C,e t a l .E ffect of d i etary P l a t yc -odon grand i florum on the i m prove m en t of i nsu li n resistance i nobese Zucker ratsJ.J Nu t

41、r B i oc h e m ,2000,11(9:420-424.34ADH I D A,M ELVI N B.S i m ple liqu i d-li qu i d partiti on s yste m f or i sol ati on of labelled oh i c aci d from m i xt u re w i th gl ycosi d esJ.J L i pi d Res ,1969,10(3:341-344.35X U B J ,ZHENG Y N ,HAN L K ,et a l .S t udy on fatm etabolis m of P la t yc

42、o d on grand i florum J.J Dalian Un i v (大连大学学报,2000,21(4:77-79.36GAO Y F ,CHEN C ,Z HANG H Y ,et al .E ffect of t otal sapon i ns of P la t yc od on g rand i f l orum on hyperli p i de m i a i n ratsJ.Chin H erb M ed (中草药,2000,31(10:764-767.37Z H ENG Y N ,LI U K Y ,X U B J ,e t a l .S t udy on the

43、ant-i obesity m echan is m of P latyc od on grand i florum J.J Jilin Ag ri c Univ (吉林农业大学学报,2002,24(6:42-44.38K I M K S ,EZAKI O,I KEM OTO S,et al .E ffects of P l a t ycodon grand i florum feed i ng on serum and liver li p i d concen trati ons i n rats w it h d i et -i nduced hyperlipide m iaJ.J N utr Sc i Vit am inol (Tokyo ,1995,41(4:485-491.39CHOI S S,HAN E J ,LEE T H,et a l .An ti nocicep tive m echa -n is m s of p l atycod i n D adm i n i stered i nt