A new acylated flavonol glycoside from the aerial parts of Cardamine tangutorum

Article abstract of DOI:10.1080/10286020.2012.692363

A new acylated flavonol glycoside, kaempferol-3-O-β-d-(2- feruloylglucopyranosyl) (1 → 6)-[β-d-glucopyranosyl(1 → 2)]-β-d-glucopyranoside, named tangutorumoside A (1), together with 12 known compounds, was isolated from 50% acetone extract of Cardamine tangutorum. Their structures were elucidated by NMR and MS experiments. In addition, compound 1 could promote the proliferation of splenic lymphocytes and thymic lymphocytes with ConA in vitro.

Full text of DOI:10.1080/10286020.2012.692363

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A new acylated flavonol glycoside
from the aerial parts of Cardamine
tangutorum
a
a
a
a
Wei-Sheng Feng , Qiu-Bo Zhang , Xiao-Ke Zheng , Hui Chen
,
a
a
Yan-Li Zhang & Chun-Lei Zhang
a
School of Pharmaceutical Science, Henan University of
Traditional Chinese Medicine , Zhengzhou , 450008 , China
Published online: 14 Jun 2012.
To cite this article: Wei-Sheng Feng , Qiu-Bo Zhang , Xiao-Ke Zheng , Hui Chen , Yan-Li
Zhang & Chun-Lei Zhang (2012) A new acylated flavonol glycoside from the aerial parts of
Cardamine tangutorum , Journal of Asian Natural Products Research, 14:8, 805-810, DOI:
10.1080/10286020.2012.692363
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Journal of Asian Natural Products Research
Vol. 14, No. 8, August 2012, 805–810
A new acylated flavonol glycoside from the aerial parts
of Cardamine tangutorum
Wei-Sheng Feng*, Qiu-Bo Zhang, Xiao-Ke Zheng, Hui Chen, Yan-Li Zhang and
Chun-Lei Zhang
School of Pharmaceutical Science, Henan University of Traditional Chinese Medicine,
Zhengzhou 450008, China
(
Received 5 December 2011; final version received 6 May 2012)
A new acylated flavonol glycoside, kaempferol-3-O-b-D-(2-feruloylglucopyranosyl)
(
1 ! 6)-[b-D-glucopyranosyl(1 ! 2)]-b-D-glucopyranoside, named tangutorumoside
A (1), together with 12 known compounds, was isolated from 50% acetone extract of
Cardamine tangutorum. Their structures were elucidated by NMR and MS
experiments. In addition, compound 1 could promote the proliferation of splenic
lymphocytes and thymic lymphocytes with ConA in vitro.
Keywords: Cardamine tangutorum; acylated flavonol glycoside; Cruciferae
1
.
Introduction
syl flavone (3) [8], kaempferol-3-O-b-D-
glucopyranosyl-(1 ! 2)-b-D-glucopyrano-
Cardamine tangutorum (Cruciferae family)
is a perennial herb and mainly distributed
in the mountains and uplands of north
and southwest ofChina. Cardamine consists
of about 130 species in the world, of which
0
side (4) [9], 5,4 -dihydroxy-7-methoxy-
6-C-[b-D-xylopyranosyl-(1 ! 2)]-b-D-glu-
0
copyranosyl flavone (5) [10], 5,4 -dihy-
droxy-7-methoxy-8-C-[b-D-xylopyranosyl-
4
2speciesarefoundinChina[1].Mostherbs
(1 ! 2)]-b-D-glucopyranosyl flavone (6)
0
of Cruciferae family have obvious biologi-
cal activities, such as antibiosis, antiviral,
and antiendotoxin [2–4]. Some glycosi-
dated compounds, such as megastigmane
glucopyranosides and kaempferol glyco-
sides,havebeenisolatedfromthisgenus[5–
[
[
10], 5,7,4 -trihydroxy-6-methoxy-8-C-
b-D-xylopyranosyl-(1 ! 2)]-b-D-gluco-
0
pyranosyl flavone (7) [11], 5,7,4 -trihy-
droxy-8-methoxy-6-C-[b-D-xylopyranosyl-
(
[
(
1 ! 2)]-b-D-glucopyranosyl flavone (8)
11], quercetin-3-O-b-D-xylopyranosyl-
1 ! 2)-b-D-galactopyranoside (9) [12],
6
]. However, few of the phytochemical
studies of the plant have been reported
previously. In our search for bioactive
compounds from this medicinally important
genus, a new acylated flavonol glycoside
named tangutorumoside A, together with 12
known compounds, kaempferol-3-O-b-D-
glucopyranosyl(1 ! 6)-[b-D-glucopyrano-
syl(1 ! 2)] -b-D-glucopyranoside (2) [7],
p-hydroxyphenylethanol (10) [13], hydro-
ferulic acid (11) [14], isovanillic acid (12)
[
[
15], and methyl p-hydroxycinnamate (13)
16], was isolated from 50% acetone extract
of C. tangutorum. All these known com-
pounds are reported from this plant for the
first time. In this paper, we report the
isolation and structural elucidation of these
compounds and the MTT proliferation
0
,4 -dihydroxy-6,7-dimethoxy-8-C-[b-D-
5
xylopyranosyl-(1 ! 2)]-b-D-glucopyrano-
Corresponding author. Email: fwsh@hactcm.edu.cn
*
ISSN 1028-6020 print/ISSN 1477-2213 online
q 2012 Taylor & Francis
http://dx.doi.org/10.1080/10286020.2012.692363
http://www.tandfonline.com

8
06
W. Feng et al.
1 13
Table 1. H (400 MHz) and C (100 MHz)
activity of compound 1 against the splenic
lymphocytes and thymic lymphocytes.
NMR spectral data of compound 1 (CD
d ppm).
3
OD,
No.
d
H
(J, Hz)
d
C
2
.
Results and discussion
2
3
4
5
6
7
8
9
158.8
134.8
179.7
163.0
100.6
167.0
95.4
158.5
105.5
122.5
132.5
116.4
161.7
Compound 1 was isolated as a yellow
amorphous powder. Its molecular formula
was deduced as C H O from the
4
3 48 24
þ
[
M þ Na þ H] peak at m/z 972.2473
6.19 (d, J ¼ 1.3)
6.43 (d, J ¼ 1.3)
using HR-ESI-MS. The IR spectrum
exhibited the absorptions of hydroxyl
2
1
21
3403 cm ), carbonyl (1654 cm ), and
(
1
1
0
2
1
aromatic rings (1604 and 1513 cm ). The
UV spectrum showed absorption maxima
at 269 and 327 nm. Upon acid hydrolysis
with 1 M HCl, 1 afforded kaempferol as its
aglycone, which was identified by com-
parison of its NMR spectral data with
those in the literature [17], and D-glucose
as a sugar component which was identified
by gas–liquid chromatographic analysis.
0
0
0
0
2 , 6
8.13 (d, J ¼ 8.8)
6.85 (d, J ¼ 8.8)
0
3 , 5
0
Glc
4
0
0
00
1
5.35 (d, J ¼ 7.5)
4.04 (m)
3.60 (m)
3.73 (m)
3.58 (m)
3.74 (m), 3.70 (m)
101.5
79.7
74.5
70.3
78.2
68.5
00
2
0
0
0
0
0
0
0
0
3
4
5
6
1
The H NMR spectrum of 1 (Table 1)
exhibited nine aromatic proton signals,
000
Glc
000
1
4.72 (d, J ¼ 6.9)
3.38 (m)
3.37 (m)
3.39 (m)
3.37 (m)
3.80 (m), 3.77 (m)
104.6
75.2
77.9
71.3
77.4
62.6
0
00
four of which resonated at d 8.13 (2H, d,
0
2
3
4
5
6
0
000
J ¼ 8.8 Hz, H-2 , 6 ), 6.85 (2H, d,
0
0
00
00
0
0
J ¼ 8.8 Hz, H-3 , 5 ), being ascribed to a
0
0
set of AA BB system of flavone B-ring.
Two deshielded one-proton doublets at d
000
0000
Glc
0
0
0
0
000
000
000
000
6
1
.19 and 6.43 with coupling interactions of
.3 Hz each were assigned to aromatic ring
1
2
3
4
5
6
4.39 (d, J ¼ 8.0)
4.58 (m)
3.13 (m)
3.34 (m)
3.50 (m)
3.59 (m), 3.69 (m)
101.9
75.4
75.9
71.5
77.3
62.2
A meta-coupled H-6 and H-8, respect-
ively. The rest of the signals at d 6.83 (1H,
0000
0000
00000
d, J ¼ 8.0 Hz, H-5 ), 7.02 (1H, dd,
00000
00000
J ¼ 8.0, 1.1 Hz, H-6 ), and 7.21 (1H, d,
Feruloyl
00000
00000
J ¼ 1.1 Hz, H-2 ) as well as a trans-
1
127.9
111.9
150.7
149.4
116.5
124.2
147.4
115.3
168.5
56.7
0
0
0000
0000
2
3
4
5
6
7
8
9
7.21 (d, J ¼ 1.1)
double bond at d 7.54 (1H, d, J ¼ 15.8 Hz,
0
0000
H-7 ) and 6.16 (1H, d, J ¼ 15.8 Hz, H-
00000
00000
0
0
0
0
0
0000
8
) were assigned to the feruloyl moiety.
6.83 (d, J ¼ 8.0)
0000
0000
0000
0000
In addition, 21 proton signals were found
in the range of d 3.13–5.35, which
suggested the existence of three glucose
7.02 (dd, J ¼ 8.0, 1.1)
7.54 (d, J ¼ 15.8)
6.16 (d, J ¼ 15.8)
13
moities. The C NMR spectrum of 1
showed important signals for two carbonyl
carbons at d 179.7 (C-4) and 168.5 (C-
ZOCH
3
3.95 (s)
1 13
Further analysis of the H and C NMR
0
0000
9
), four double band carbons at d 158.8
00000
spectra of 1 revealed the presence of three
0
(C-2), 147.4 (C-7 ), 134.8 (C-3), and
0
0
0000
sugars at d 5.35 (1H, d, J ¼ 7.5 Hz, H-1 ),
1
9
15.3 (C-8 ), three aromatic rings at d
5.4–167.0, as well as three glucose
0
00
4.72 (1H, d, J ¼ 6.9 Hz, H-1 ), and 4.39
0
000
moieties (d 62.2–104.6), respectively.
(1H, d, J ¼ 8.0 Hz, H-1 ), which were

Journal of Asian Natural Products Research
correlated in the HSQC spectrum with
807
2'
3'
8
three anomeric carbons at d 101.5, 104.6,
and 101.9, respectively. The coupling
constants of three anomeric protons
demonstrated that the glucoses were in
b-orientation. Complete assignment of
each glycosidic proton system was rea-
lized from the combined analysis of
O
1'
4'
HO
7
OH
9
1
2
0
6
5
6'
5'
3
4
O
HO
OH
O
1'''
1''
O
O
O
OH
OH
O
1
1
1''''
HO
H– H COSY, TOCSY, HSQC, and
O
OH
O
OH
8
1
HMBC spectra. Specifically, the H– H
1
6'''''
'''''
5'''''
C
HO
4
'''''
COSY and HSQC spectra of 1 confirmed
00
1'''''
OH
0
0
000
HO
OH
O
7'''''
the presence of CH(1 )-CH(2 ), CH(1 )-
3
'''''
0
00
0000
0000
2'''''
CH(2 ), and CH(1 )ZCH(2 ) units. The
sequence of the glycosidic chain in 1 was
determined by the analysis of the 2D NMR
spectroscopic data. The key HMBC
OCH3
Figure 1. The chemical structure and selected
HMBC correlations of compound 1.
00
correlations from Glc-H-1 (d 5.35) to
C-3 (d 134.8) indicated unambiguously
0000
moiety was connected to C-2 of the
glucosyl moiety. Thus, the structure of
0
0
that the Glc residue was linked to C-3 of
the aglycone. The long-range correlations
observed between the anomeric proton at d
1
was determined to be kaempferol-3-O-b-
D-(2-feruloylglucopyranosyl)(1 ! 6)-[b-
D-glucopyranosyl(1 ! 2)]-b-D-glucopyr-
anoside (Figure 1).
000
4
.72 (Glc-H-1 ) and the carbon at d 79.7
00 0000
(
Glc-C-2 ), and between Glc-H-1 at d
00
.39 and Glc-C-6 at d 68.5 indicated that
the trisaccharide residue at C-3 of the
4
The cell viability of compound 1 was
tested on Balb/c mice splenic lymphocytes
and thymic lymphocytes with ConA by the
MTT method in vitro. According to the
results (Figure 2), compound 1 could
promote the proliferation of splenic
lymphocytes and thymic lymphocytes.
aglycone is b-D-glucopyranosyl-(1 ! 6)-
[
pyranoside. In addition, the HMBC
b-D-glucopyranosyl-(1 ! 2)]-b-D-gluco-
0
000
correlation from Glc-H-2 (d 4.58) to
0000
0
C-9 (d 168.5) confirmed that the feruloyl
(a)
200
(b)
200
180
160
140
120
100
80
1
1
1
1
1
80
60
40
20
00
8
0
0
6
60
Concentrations
µg/ml)
Con A(5µg/ml)
Concentrations
(µg/ml)
Con A(5µg/ml)
–
–
–
0.1
+
1
10
+
–
–
–
0.1
+
1
10
+
(
+
+
+
+
Figure 2. Effects of compound 1 on proliferation of splenic lymphocytes and thymic lymphocytes
by MTT assay in vitro. Thymic lymphocytes (a) and splenic lymphocytes (b) were both treated with
vehicle, Con A (5 mg/ml), 0.1, 1, 10 mg/ml of compound 1, along with Con A (5 mg/ml) as indicated
(O, p , 0.01, compared to the vehicle-treated cells; w, p , 0.01, compared to the Con A-treated
cells).

8
08
W. Feng et al.
3
.
Experimental
20100702) has been deposited in our
laboratory.
3
.1 General experimental procedures
Optical rotations were obtained on a Perkin-
Elmer 341 polarimeter (PerkinElmer Cor-
poration, Waltham, MA, USA). UV spectra
were measured with a Shimadzu UV–vis
3
.3 Extraction and isolation
Dried aerial parts of C. tangutorum (2.5kg)
wereextracted with 50% ofaqueous acetone
twiceatroomtemperature, andconcentrated
under reduced pressure below 458C. The
water-soluble part (150g) was chromato-
2
201 spectrophotometer (Shimadzu Cor-
poration, Kyoto, Japan). IR spectra were
measured with a Shimadzu FTIR-8201 PC
1
spectrometer (Shimadzu Corporation). H
1
3
graphed over Diaion HP-20 with H
containing increasing amounts of MeOH to
afford H O eluate 21.5g (A), 10% MeOH
eluate 8.32g (B), 30% MeOH eluate 20.3g
C), and 40% MeOH eluate 18.5g (D).
O
2
and C NMR spectra were obtained on a
Bruker DPX-400 spectrometer (400MHz
1
13
2
for H NMR and 100 MHz for C NMR)
with TMS as an internal reference (Bruker
Corporation, Ettlingen, Germany). HR-ESI-
MS were recorded on a Bruker APEX II
spectrometer in positive-ion mode (Bruker
Corporation). Gas chromatography (GC)
data were recorded on an Agilent 7890A
instrument (Agilent Technologies Corpor-
ation, Santa Clara, CA, USA). Column
chromatography was carried out on Diaion
HP-20 (Mitsubishi Chemical Corporation,
Tokyo, Japan), silica gel (160–200 mesh,
Qingdao Marine Chemical Industry,
Qingdao, China), Toyopearl HW-40, and
Sephadex LH-20 (TOSOH Corporation,
Tokyo, Japan). TLC was conducted on
self-made silica gel G (Qingdao Marine
Chemical Industry) plates. Cell viability
was quantitatively measured by the MTT
(
Fraction A was chromatographed on
Toyopearl HW-40 (coarse grade) develop-
ing with 10% MeOH–50% MeOH. The
1
rechromatographed on Toyopearl HW-40
0% MeOH eluate (6.4 g) of A was
(
(
50% MeOH) to yield compound 3
10.1 mg). The 20% MeOH eluate (4.3g)
of A was rechromatographed on Toyopearl
HW-40 (70% MeOH) and on silica gel
(CHCl –MeOH–H O, 6:1:0.1) to yield
3 2
compounds 4 (15.2 mg) and 5 (25.2 mg).
Fraction B was chromatographed on Toyo-
pearlHW-40(coarsegrade)developingwith
1
0% MeOH–50% MeOH. The 10% MeOH
eluate (7.1g) of B was rechromatographed
on Toyopearl HW-40 (70% MeOH) and on
silica gel (CHCl –MeOH, 10:1) to yield
3
(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-
compounds 6 (11 mg) and 7 (15 mg). The
tetrazolium bromide) assay with a BIO-
RAD Model 680 micro-plate reader (BIO-
RAD Corporation, Hercules, CA, USA).
The chemical reagents were supplied by
Beijing Chemical Plant (Beijing, China)
and Tianjin No. 3 Reagent Plant (Tianjin,
China).
2
0% MeOH eluate (5.4 g) of B was
rechromatographed on Toyopearl HW-40
MeOH) and on silica gel (CHCl –MeOH,
(
3
8
:1:0.05) to yield compounds 8 (25 mg), 9
11 mg), and 10 (11 mg). Fraction C was
chromatographed on Toyopearl HW-40
coarse grade), developing with 10%
(
(
MeOH–50% MeOH. The 10% MeOH
eluate (6.8g) of C was rechromatographed
on Toyopearl HW-40 (MeOH) and on silica
3
.2 Plant material
Air-dried aerial plants of C. tangutorum
were collected in May 2010 from Xixia
County, Henan Province of China, and
identified by Prof. Cheng-Ming Dong of the
Henan University of Traditional Chinese
Medicine. A voucher specimen (No.
gel (EtOAc–EtOH–H O, 12:2:1) to yield
2
compounds 1 (12 mg), 2 (21 mg), and 13
(15 mg). Fraction D was chromatographed
on Toyopearl HW-40 (coarse grade), devel-
oping with 10% MeOH–50% MeOH. The
10% MeOH eluate (15.6 g) of D was

Journal of Asian Natural Products Research
809
rechromatographed on Toyopearl HW-40
MeOH)toyield compounds 11(12 mg)and
reported protocol [18]. Briefly, the splenic
lymphocytes and thymic lymphocytes were
isolated from the Balb/c mice in sterile
conditions. Then, the lymphocytes were
suspended by treatment with trypsin
(
1
2 (12 mg).
3
.3.1 Kaempferol-3-O-b-D-
(0.25%) and were maintained in 1640
(
2-feruloylglucopyranosyl)(1 ! 6)-
b-D-glucopyranosyl(1 ! 2)]-
b-D-glucopyranoside (1)
medium. After that, the cells were plated
into 96-well (30,000 and 40,000 cells/well,
respectively) tissue confluence plates.
The medium was replaced by new medium
containing compound 1 (0.1, 1, and
[
20
Yellow amorphous powder. ½aꢀ 217
D
(
c ¼ 0.12, MeOH); IR (KBr) n : 3403,
max
21
925, 1654, 1604, 1513, 1178, 1076cm ;
2
UV (MeOH) l : 269, 327 nm. H and
1
0 mg/ml, respectively) after the cells
1
max
reached confluence. To observe the cell
proliferation, MTT assay was carried out
after 24h and 48h cultivation, respectively.
1
3
C NMR spectral data are shown in
Table 1. HR-ESI-MS: m/z 972.2473
þ
[
M þ Na þ H] (calcd for C H O Na,
4
3 49 24
9
72.2512).
Acknowledgments
This work was financially supported by the
Ministry of Education of China (2003078) and
program for Science & Technology Innovation
Talents in Universities of Henan Province
3
.4 Acid hydrolysis of compound 1
Compound 1 (2 mg) was dissolved in 1 M
HCl (aq) (5 ml) and heated at 908C for 2 h
under constant stirring. After extraction
with EtOAc (3 £ 5 ml), the aqueous layer
was evaporated and cryodesiccated. The
residue was dissolved in dry pyridine
(
2010HASTIT014). We thank Prof. Cheng-
Ming Dong (Henan University of Traditional
Chinese Medicine, China) for the original plant
collection and identification.
(
1 ml), and then L-cysteine methyl ester
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