全 文 ：The first au thor:Ph. D. candidate at Zhejiang Un iversity.
* C orresponded au thor:Tel 0571-87217313;Fax 0571-87217313;E-m ail d ryuzhao@ z ju. edu. cn
论　著
F lavonol and m onoterpene glycosides from L igularia macrophy lla
PAN Yun-xue1, 2 , DOU Hu i1 , ZHENG X iao-xiang2 , GAO X iao-zhong1 , ZHOU Chang-x in1 , ZHAO Yu1*(1. D epart-
m ent of T raditional ChineseMed icine and Na tura lD rug Research , College of Pharmaceutica l Sciences, Zhejiang University, Hangzhou
310031, Ch ina;2. D epartm ent of B iom edica lEngineering , College of B iom edical Engineering and Instrum ent S ciences, Zhejiang Un i-
versity, Hangzhou 310006, China )
ABSTRACT:OBJECTIVE　 To investigate the chem ical constituents o f the roo ts and rhizom es o f L igularia macrophy lla.
METHOD S　The com pounds we re iso la ted th rough repea ted co lum n ch rom a tog raphy on silica g el, po lyam ide, RP-18 and Sephadex
LH-20. And the structure s w ere e lucidated on the basis o f spec tro scop ic da ta (UV , IR, MS, 1H NMR, 13C NMR, DEPT and 2D
NMR). RESULTS　Fou r flavono l g lycosides and tw o m ono te rpene g ly coside s we re ob tained and determ ined as rham nazin-3-O-β-D-
rutinoside (1), rham netin-3-O-β-D-ru tino side (2), rutin(3), afze lin(4), betula lbuside A (5) and 3, 7-dim ethy loct-1-en-3, 8-dio l-
8-O-β-D-g lucopy rano side (6). CONCLUSION　A ll the compounds w ere iso lated from th is plan t fo r the first tim e.
KEY WORDS:L igularia macrophy lla;compositae;flavono l g lycosides;monoterpene g ly co sides
大叶橐吾中的黄酮醇苷和单萜苷
潘云雪 1, 2 , 窦辉 1 , 郑筱祥 2 , 高晓忠 1 , 周长新 1 , 赵昱 1*(1. 浙江大学药学院中药与天然药物研究室 ,浙江　杭州 310031;2.
浙江大学生物医学工程与仪器科学学院 ,浙江　杭州 310006)
摘要:目的　研究大叶橐吾的化学成分。方法　应用多种色谱方法和色谱材料进行提取 、分离和纯化 ,用各种现代光谱方法解
析结构。结果　从大叶橐吾根茎的乙醇提取物中分离纯化到四个黄酮醇苷和两个单萜苷 , 分别为甲基鼠李素-3-O-β-D-芸香
糖苷(1), 鼠李素-3-O-β-D-芸香糖苷(2), 芦丁(3),阿福豆苷(4),桦木苷(5)和 3, 7-d im ethy loct-1-en-3, 8-dio l-8-O-β-D-g lucopy r-
ano side (6)。结论　所有化合物均为首次从该种植物中分离纯化得到。
关键词:大叶橐吾;菊科;黄酮醇苷;单萜糖苷
中图分类号:R284. 1　　　文献标识码:A　　　文章编号:1007-7693(2005)03-0175-04
Introduction
L igularia macrophy lla DC. is a trad itional Ch inese m edici-
nal herb used as an titussives. Pharm aco log ic study revea led tha t
the crude ex trac t of the p lant exhibits antibacte ria l and antineo-
p lastic activ ities as we ll a s reliev ing cough and e lim ina ting the
phlegm [ 1] . So fa r, the re are only a few repo rts abou t its chem ica l
constituen ts[ 2-4] . Our phy tochem ica l investiga tion on the ethanol-
ic extract o f its roo ts and rh izom es re su lted in the isola tion o f six
compounds including four flavono l g lycoside s, rham nazin-3-O-β-
D-ru tinoside (1), rham netin-3-O-β-D-rutino side (2), que rce-
tin-3-O-β-D-ru tino side (3), kaem pfero l-3-O-α-L-rhamnopy rano-
side (4), and tw om ono terpene g lycosides, betula lbuside A (5)
and 3, 7-dim e thy loc t-1-en-3, 8-dio l-8-O-β-D-g lucopy rano side
(6). A ll the com pounds w ere firstly iden tified from the title
p lan.t This pape r deals w ith the iso la tion and characterization of
the six g ly co side s.
P lan tm ater ia l
The plan tw as co llected from Lijiang county, Yunnan prov-
ince, China, in August 2001 and taxonom ica lly au then ticated by
P ro .f P eng Hua from Kunm ing Institu te of Bo tany, Chinese
A cademy o f Science s. A voucher spec im en ( No.
20010820ZY010) was deposited at theH erbarium of the Depart-
m en t o f Pha rmacognosy, Co llege of Pharm aceutica l Sc iences,
Zhejiang Un ive rsity.
General exper im en tal
Melting points we re observed on an X-4 dig ita l appara tus
and a re uncorrec ted. Optical ro ta tionsw e rem easured w ith a Po-
lax-2L polarim eter. UV spectra we re recorded w ith a UV-1600
spec tropho tome ter. IR spectra we re recorded as KB r pa llets w ith
a BrukerVec to r-22 spec trom eter. MS spec tra we re exam ined on
175 中国现代应用药学杂志 2005年 6月第 22卷第 3期　　　　　　　　　　　　　　　Ch in JMAP , 2005 Ju ly, Vo.l 22 No. 3
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an E squire-LC-00075 mass spectrom e ter. NMR spectraw ere run
on an INOVA-400 instrum ent w ith TM S as an inte rna l standa rd.
Extract ion and isolat ion
The air dried and pow de red roo ts and rhizomes o fL. m acro-
phy lla (2. 0 kg) was ex tracted w ith 95% e thano l(5L×4) a t
room tem pe ra ture. Evapo ra tion o f the so lven t unde r reduced
pressure gave the crude extract (240 g), w hich w as suspended
in w ate r and partitioned w ith petro leum e the r, e thy l ace tate and
n-bu tano l, successive ly. The n-BuOH ex tract(80 g) was chro-
m atographed on silica gel(1. 0 kg) e luted w ith CHC l3-M eOH a t
inc reasing po larities to y ie ld ten fractions. Furthe r sepa ra tion of
fraction Ⅶ by po lyam ide and the Sephadex LH-20 co lum n chro-
m atography a ffo rded com pounds 1 and 2. Com pound 3 w as cry s-
ta llized from fraction Ⅷ and pu rified through recry sta llization in
M eOH. Compound 4 w as ob ta ined from fraction Ⅲ by prepa ra-
tive TLC p la te s deve loped by CHC l3-M eOH (5∶1). F rac tion Ⅴ
and Ⅵ we re repeatedly chrom atog raphed on silica g el, RP-18
and Sephadex LH -2 0 co lum ns to g ive com pounds 5 and 6,
re spec tively.
Struc ture ident ificat ion
Com pound 1 C29 H34 O16 , pa le ye llow am o rphous powder
(M eOH), w ith a positive reaction to M olish andMg-HC l tests.
m p 156-158℃;UV (M eOH ) λ
m ax
nm:253, 353; IR (KBr)
cm - 1:3380 (OH), 1650 (C =O), 1607, 1502 (C =C);
ES I-M Sm /z:639 [M +H] +, 493[M +H -rha] +, 331[M
+H -rha-g lc] +;1H NMR (DM SO-d6)δ:0. 97 (3H , d, J
=6. 4 H z, M e of rhamnose), 3. 85 (3H , s, M eO-7), 3. 87
(3H , s, M eO-3′), 4. 41(1H , brs, H-1′″of rhamnose), 5. 44
(1H , d, J = 7. 6 H z, H-1″of g luco se), 6. 37 (1H , d, J =
2. 0 H z, H-6), 6. 71(1H , d, J =2. 0 H z, H-8), 6. 92 (1H ,
d, J =8. 4 H z, H-5′), 7. 57(1H , dd, J =8. 4, 2. 0 H z, H-
6′), 7. 87 (1H , d, J = 2. 0 H z, H-2′), 9. 71 (1H , b rs, 4′-
OH), 12. 56 (1H , brs, 5-OH). 13C NMR da ta see Table 1.
Above da ta we re in acco rd w ith tho se of rhamnazin-3-O-β-D-ruti-
noside[ 5] . Therefo re, com pound 1 was identified as rhamnazin-3-
O-β-D-rutinoside.
Tab 1　13C NMR data (δ in DMSO-d6) fo r com pounds 1-6
表 1　化合物 1-6的碳谱数据(氘代 DMSO, δ)
carbon 1 2 3 4* 5 6
1 111. 2 ( t) 111. 0 ( t)
2 156. 6 (s) 156. 7 (s) 156. 8 (s) 157. 9 (s) 146. 3 (d) 146. 6 (d)
3 133. 5 (s) 133. 6 (s) 133. 5 (s) 135. 6 (s) 71. 6 (s) 71. 7 (s)
4 177. 7 (s) 177. 6 (s) 177. 5 (s) 179. 2 (s) 42. 1 ( t) 42. 7 ( t)
5 161. 1 (s) 161. 2 (s) 161. 5 (s) 163. 1 (s) 22. 2 ( t) 21. 0 ( t)
6 98. 2 (d) 98. 2 (d) 99. 3 (d) 99. 5 (d) 128. 1(d) 33. 7 ( t)
7 165. 3 (s) 165. 3 (s) 165. 5 (s) 165. 0 (s) 131. 5 (s) 33. 3 (d)
8 92. 6 (d) 92. 4 (d) 94. 1 (d) 94. 5 (d) 73. 8 ( t) 74. 4 ( t)
9 157. 1 (s) 157. 6 (s) 156. 8 (s) 158. 4 (s) 27. 9 (q) 27. 9 (q)
10 105. 2 (s) 105. 3 (s) 103. 9 (s) 105. 7 (s) 14. 0 (q) 17. 1 (q)
1′ 121. 1 (s) 120. 0 (s) 121. 4 (s) 122. 4 (s)
2′ 113. 6 (d) 115. 8 (d) 115. 6 (d) 131. 6 (d)
3′ 149. 9 (s) 145. 9 (s) 145. 2 (s) 116. 3 (d)
4′ 147. 2 (s) 151. 0 (s) 148. 9 (s) 160. 9 (s)
5′ 115. 5 (d) 116. 4 (d) 116. 5 (d) 116. 3 (d)
6′ 122. 7 (d) 122. 1(d) 121. 9 (d) 131. 6 (d)
7-OM e 56. 3 (q) 56. 3 (q)
3′-OMe 55. 9 (q)
g lc
1″ 101. 3 (d) 101. 6 (d) 101. 6 (d) 101. 7 (d) 103. 5 (d)
2″ 74. 5 (d) 74. 4 (d) 74. 4 (d) 73. 6 (d) 73. 7 (d)
3″ 76. 6 (d) 76. 8 (d) 76. 8 (d) 77. 1 (d) 77. 0 (d)
4″ 70. 4 (d) 70. 3 (d) 70. 3 (d) 70. 4 (d) 70. 4 (d)
5″ 76. 2 (d) 76. 2 (d) 76. 2 (d) 77. 1 (d) 77. 0 (d)
6″ 67. 1 ( t) 67. 2 ( t) 67. 3 ( t) 61. 3 ( t) 61. 3 ( t)
rha
1″′ 101. 1 (d) 101. 2 (d) 101. 1 (d) 102. 6 (d)
″′ 70. 5 (d) 70. 6 (d) 70. 7 (d) 71. 4 (d)
3″′ 70. 8 (d) 70. 8 (d) 70. 9 (d) 72. 1 (d)
4″′ 72. 0 (d) 72. 2 (d) 72. 2 (d) 72. 9 (d)
5″′ 68. 5 (d) 68. 6 (d) 68. 6 (d) 71. 3 (d)
6″′ 17. 9 (q) 18. 1 (q) 18. 1 (q) 17. 7 (q)
*:δin acetone-d6
176 Ch in JMAP, 2005 Ju ly, Vo.l 22 N o. 3　　　　　　　　　　　　　　　中国现代应用药学杂志 2005年 6月第 22卷第 3期
　　 Com pound 2 C28 H32 O16 , pa le yellow amo rphous pow de r
(M eOH), mp 202-204℃;UV (M eOH) λm ax nm:255, 355;
IR (KBr) cm - 1:3375(OH), 1630 (C =O), 1605, 1500(C
=C);ESI-MSm /z:625 [M +H] +, 479 [M +H -rha] +,
317 [ M + H -g lc-rha] +;1H NMR (DMSO-d6) δ:0. 99
(3H , d, J = 6. 4 H z, M e o f rham nose), 3. 85 (3H , s, M eO-
7), 4. 39 (1H , brs, H-1′″o f rham nose), 5. 29 (1H , d, J =
7. 6 H z, H-1″o f g lucose), 6. 34(1H , d, J =2. 0 H z, H-6),
6. 67 (1H , d, J = 2. 0 H z, H-8), 6. 74 (1H , d, J = 8. 8
H z, H-5′), 7. 56 (1H , d, J = 2. 0 H z, H-2′), 7. 59 (1H ,
dd, J =8. 8, 2. 0 H z, H-6′), 12. 89 (1H , b rs, 5-OH). 13C
NMR data see Tab le 1. Above data we re in ag reem ent w ith those
o f rhamnetin-3-O-β-D-rutino side[ 6] .
Com pound 3 C27H30O 16 , yellow needle c rysta ls (M eOH),
m p 176-178℃;UV (M eOH) λm ax nm:258, 357;IR (KBr)
cm - 1:3420 (OH), 1656 (C =O), 1602, 1502 (C =C);
ES I-M Sm /z :611 [ M +H] +, 465 [ M +H -rha] +, 303
[ M +H -g lc-rha] +;1H NMR (DM SO-d6) δ:1. 00 (3H ,
d, J = 6. 0 H z, M e o f rhamnose), 4. 40 (1H , d, J = 1. 6
H z, H-1′″of rhamnose), 5. 32 (1H , d, J =7. 2 H z, H-1″of
g lucose), 6. 15 (1H , d, J =2. 0 H z, H-6), 6. 35(1H , d, J
=2. 0 H z, H-8), 6. 83 (1H , d, J = 8. 4 H z, H-5′), 7. 52
(1H, d, J = 2. 0 H z, H-2′), 7. 54 (1H , dd, J = 8. 4, 2. 0
H z, H-6′), 12. 89(1H , brs, 5-OH). 13C NM R data see Tab le
1. Above da ta w e re consistent w ith those of que rce tin-3-O-β-D-
rutinoside ( rutin)[ 7] .
Com pound 4 C21H20O 10 , yellow needle c rysta ls (M eOH),
m p 175-178℃;UV (M eOH) λm ax nm:266, 344;IR (KBr)
cm - 1:3300 (OH), 1660 (C =O), 1610, 1500 (C =C);
ES I-M Sm /z:433 [ M +H] +, 287 [ M + H -rha] +, 1H
NMR (Acetone-d6) δ:0. 86 (3H , d, J = 6. 0 H z, M e of
rham nose), 5. 50 (1H, d, J = 1. 6 H z, H-1″o f rhamnose),
6. 23 (1H , d, J = 2. 0 H z, H-6), 6. 43 (1H , d, J = 2. 0
H z, H-8), 6. 98 (2H, d, J = 8. 8 H z, H-3′, 5′), 7. 81
(2H , d, J = 8. 8 H z, H-2′, 6′), 9. 29 (1H , brs, 7-OH),
9. 91 (1H , brs, 4′-OH), 12. 68 (1H , brs, 5-OH). 13C NMR
data see Tab le 1. Above data we re in acco rd w ith tho se of
kaem pfero l-3-O-α-L-rhamnopy ranoside (afze lin)[ 8] .
Com pound 5 C16H28O7 , co lourless o il;[ α] 28D– 16. 3°(c
0. 50, M eOH );ES I-M Sm /z:355 [M +Na] +, 333 [ M +
H] +, 315 [M +H -H
2
O ] +, 153 [ 315 -g lc] +;1H NMR
(DMSO-d6)δ:1. 15 (3H , s, M e-9), 1. 43 (2H , t, J = 8. 0
H z, H-4), 1. 59 (3H, s, M e-10), 1. 99 (2H , m , H-5),
3. 88(1H , d, J =12. 0 H z, H-8a), 4. 07(1H , d, J =12. 0
H z, H-8b), 4. 08 (1H , d, J = 8. 0 H z, H-1″o f g lucose),
4. 95 (1H , b rd, J = 10. 8 H z, H-1a), 5. 14(1H , b rd, J =
17. 2 H z, H-1b), 5. 40 (1H , t, J = 6. 0 H z, H-6), 5. 86
(1H , dd, J = 17. 2, 10. 8 H z, H-2). 13C NM R data see Tab le
1. Above da ta we re in conform ity w ith tho se o f be tu la lbuside
A [ 9] .
Com pound 6 C16H30O7 , co lourless o il;[ α] 28D– 50. 3°(c
0. 50, M eOH );ES I-M Sm /z:357 [ M +Na] +, 335 [ M +
H] +, 317 [M +H -H2O ] +, 155 [ 317 -glc] +;1H NMR
(DMSO-d
6
) δ:0. 87 (3H , d, J = 6. 8 H z, Me-10), 1. 03
(1H , m , H-6a), 1. 13 (3H , s, M e-9), 1. 15 (1H , m , H-
6b), 1. 35 (2H , m , H-4), 1. 36(2H, m , H-5), 1. 64 (1H ,
m , H-7), 3. 45 (1H , dd, J = 12. 0, 6. 0 H z, H-8a), 3. 66
(1H , dd, J =12. 0, 6. 0 H z, H-8b), 4. 08(1H, d, J =7. 6
H z, H-1″of g luco se), 4. 92 (1H , brd, J = 10. 8 H z, H-1a),
5. 11 (1H , b rd, J = 17. 2 H z, H-1b), 5. 85 (1H , dd, J =
17. 2, 10. 8H z, H-2). 13C NMR data see Tab le 1. Above da ta
w ere in agreem en tw ith those o f 3, 7-dime thy loc t-1-en-3, 8-diol-8-
O-β-D-g lucopyranoside[ 10] .
F ig 1　Struc tu res o f com pounds 1-6
图 1　化合物 1 ～ 6的化学结构
References
[ 1] Jiangsu Col lege of New M ed icine. D iction ary of T rad itional Ch i-
n ese Medicines [M ] . ed 1. Shanghai:Shanghai Science and
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[ 2] Fu B, Zhu QX, Yang XP, et a l. N ew sesqu iterpenes from Ligu-
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1987, 23 (1):118.
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[ 6] M ahm oud AMN, H assan IES, H eba HB. The flavonoids of
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[ 8] K ash iw ada Y , N onaka G, N ish ioka I. S tud ies on Rhubarb. V.
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收稿日期:2004-03-12
基金项目:国家自然科学基金资助项目(No. 30472112);浙江省中医药管理局点资助项目(N o. 2003KF001);浙江省科技厅计划重点资助
项目(No. 2004C 33106)。
作者简介:肖幸丰 ,男 , 27岁,硕士研究生 ,研究方向:中药药理学。
*通讯作者:楼宜嘉 , Tel /Fax:86-571-87217206, E-m ail:yi jialou@ z ju. edu. cn
淫羊藿苷伍用三七总皂苷对 Aβ-淀粉肽25-35侧脑室注射所致大鼠行为异
常及脑组织 AchE活性的影响
肖幸丰 1 ,郑明 1 ,瞿林海 1 ,张幸国 2 ,楼宜嘉 1*(1.浙江大学药学院 ,浙江　杭州 310031;2.浙江大学医学院附属第一医院 ,浙江　
杭州 310003)
摘要:目的　研究淫羊藿苷( ica riin, ICA)伍用三七总皂苷 (Panax notog inseng saponins, PNS)对 Aβ-淀粉肽 25-35(beta-amy loid
pep tide25-35 , β-AP25-35)大鼠侧脑室注射空间学习和记忆障碍的影响。方法　取经跳台法和八臂迷宫法筛选的正常大鼠采用侧
脑室注射 β-AP25-35 ,制成阿尔茨海默病(A lzhe im ers disease, AD)大鼠模型 , 应用跳台法和八臂电迷宫法判断给药前后大鼠的
空间学习和记忆能力;采用化学比色法测定脑组织中乙酰胆碱酯酶 (acety lcho line ste rase, AchE)活性。结果　与溶剂组大鼠
相比 , 模型大鼠八臂电迷宫错误次数明显增加(P <0. 05), 跳台学习和记忆错误次数明显增加(P <0. 01)。大鼠造模前后连
续 ig ICA+PNS 5+40, 10+80m g /kg 21d后 , 模型大鼠上述行为学指标得到明显改善(P <0. 05),脑组织 AchE活性降低(P <
0. 05)。结论　 ICA伍用 PNS(5+40, 10+80m g /kg)对 β-AP25-35侧脑室注射所致大鼠空间学习和记忆障碍有显著的预防和治
疗作用 , 该作用与降低脑组织中 AchE活性呈相关性。
关键词:淫羊藿苷;三七总皂苷;阿尔茨海默病模型;跳台法;八臂电迷宫法;乙酰胆碱酯酶
中图分类号:R285. 5　　　文献标识码:A　　　文章编号:1007-7693(2005)03-0178-04
E ffec ts of icar iin combined w ith the Panax notoginseng sapon ins on behavior and acetylcholinesterase activi-
ty induced by β-amylo id peptide 25-35 lateral ventr icle injection in rats
XIAO X ing-feng1 , ZHENG M ing1 , QU Lin-hai1 , ZHANG X ing-guo2 , LOU Y i-jia1*(1. College of Pharm aceutical Sci-
ences, Zhejiang University, Hangzhou 310031, Ch ina. 2. Pharmacy Departm en t, theF irst Affiliated Hospital, College ofMed icine, Zhe-
jiang University, Hangzhou, 310003, China)
ABSTRACT:OBJECTIVE　To investiga te the preventive and therapeutica l e ffec ts of ica riin( ICA) com bined w ith the Panax no tog-
inseng saponins(PNS) on spac ial lea rning and mem ory dysfunc tion o f A lzhe im ers disease (AD) model in ra ts induced by β-amy loid
pep tide25-35(β-AP25-35) la tera l ventricle injection. METHODS　After successfully tra ined by 8-a rm radial e lec tricm aze and step-dow n
passive avo idance te st, the rats we re adm in istra ted late ra l ven tric le injection w ith β-AP25-35 fo llowed by one week o f drug pre-treatm en.t
Spac ia l lea rning and m emo ry abilityw ere eva lua ted by 8-arm radial e lec tricm aze and step-down passive avo idance te st after a period of
178 Ch in JMAP, 2005 Ju ly, Vo.l 22 N o. 3　　　　　　　　　　　　　　　中国现代应用药学杂志 2005年 6月第 22卷第 3期