Gout prophylactic constituents from the flower buds of Lonicera japonica

Article abstract of DOI:10.1016/j.phytol.2015.11.016

Two new sesquiterpene glycosides (R)-dehydroxyabscisic alcohol β-d-apiofuranosyl-(1″ → 6′)-β-d-glucopyranoside (1) and (-)-(1S,2R,6R,7R)-1,2,6-trimethyl-8-hydroxy methyltricyclic[5.3.1.0^2,6]-undec-8-en-10-one β-d-apiofuranosyl-(1″ → 6′)-β-d-glucopyranoside (2), were isolated from the flower buds of Lonicera japonica. Their structures were determined by spectroscopic and chemical methods. Compound 2 could significantly decrease monosodium urate-mediated cytokine production from activated macrophage through lowering IL-1β and TNFα.

Full text of DOI:10.1016/j.phytol.2015.11.016

Phytochemistry Letters 15 (2016) 98–102
Contents lists available at ScienceDirect
Phytochemistry Letters
journal homepage: www.elsevier.com/locate/phytol
Short communication
Gout prophylactic constituents from the flower buds of Lonicera
japonica
a
b
c
c
c,
Jing-Ren Xu , Guo-Feng Li , Jia-Yi Wang , Jie-Ru Zhou , Jie Han *
a
Department of Traditional Chinese Orthopedics, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
Department of Emergency Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
Department of Rheumatology and Immunology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
b
c
A R T I C L E I N F O
A B S T R A C T
0
0
0
b
Article history:
Two new sesquiterpene glycosides (R)-dehydroxyabscisic alcohol
b
-D
-apiofuranosyl-(1 !6 )-
-D-
Received 12 October 2015
Received in revised form 23 November 2015
Accepted 25 November 2015
Available online xxx
2,6
glucopyranoside (1) and (ꢀ)-(1S,2R,6R,7R)-1,2,6-trimethyl-8-hydroxy methyltricyclic[5.3.1.0 ]-undec-
00
0
b
8
-en-10-one
Lonicera japonica. Their structures were determined by spectroscopic and chemical methods. Compound
could significantly decrease monosodium urate-mediated cytokine production from activated
macrophage through lowering IL-1 and TNF
b
-
D
-apiofuranosyl-(1 !6 )-
-D-glucopyranoside (2), were isolated from the flower buds of
2
b
a.
Keywords:
ã 2015 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.
Lonicera japonica
Sesquiterpene glycoside
Gout
Monosodium urate
1
. Introduction
was deduced from HR-ESI-MS. The IR spectrum showed hydroxyl
ꢀ
1
ꢀ1
(
3387 cm ), double bond (3022 cm ) and conjugated carbonyl
ꢀ
1
1
The flower buds of Lonicera japonica Thunb. are used to treat
cold fever, influenza, and infections in traditional Chinese
medicine (Tzeng et al., 2015). Many constituents such as caffeoyl
quinic acids, phenolic acid, flavonoids, secoiridoids, saponins,
cerebrosides and polyphenols were isolated from this plant (Bi
et al., 2008; Jiang, 2015; Kakuda et al., 2000; Kumar et al., 2005;
Kumar et al., 2006; Lin et al., 2008; Ni et al., 2015; Teng et al., 2000;
Yu et al., 2008; Yu et al., 2015; Zheng et al., 2012). To further assess
its chemical and biological diversities, we analyzed the chemical
constituents from the aqueous extract of the flower buds of L.
japonica, leading to the isolation of two new sesquiterpene
(1637 cm ) groups. The H NMR spectrum (Table 1) of 1 showed
signals including two tri-substituted double bonds at dH 5.85 (s, H-
4) and 5.66 (d, J = 7.0 and 6.5 Hz, H-10); a trans-di-substituted
double bond at dH 5.67 (dd, J = 15.5 and 9.5 Hz, H-7) and 6.28 (d,
J = 15.5 Hz, H-8); an oxygen-connecting methylene at dH 4.33 (dd,
J = 12.5 and 6.5 Hz, H-11a) and 4.14 (dd, J = 12.5 and 7.0 Hz, H-11b);
an aliphatic methylene at
J = 16.5 Hz, H-2b); an aliphatic methine at
); and four methyl groups at 1.71 (3H, s, H-12), 1.87 (3H, s, H-
3), 0.92 (3H, s, H-14), and 0.85 (3H, s, H-15). Additionally, the
d
H
2.46 (d, J = 16.5 Hz, H-2a) and 1.93 (d,
d
H
2.62 (dd, J = 9.5 Hz, H-
6
d
H
1
spectrum showed two characteristic signals for glycosyl units with
0
0
glycosides (R)-dehydroxyabscisic alcohol
b
-D
-apiofuranosyl-(1
0
anomeric protons at
d
H
4.16 (d, J = 8.0 Hz, H-1 ) and 4.82 (d,
0
!
6 )-
b
-D-glucopyranoside (1) and (ꢀ)-(1S,2R,6R,7R)-1,2,6-tri-
00
13
J = 3.0 Hz, H-1 ), respectively. The C NMR spectrum (Table 1) of 1
2
,6
methyl-8-hydroxy methyltricyclic[5.3.1.0 ]-undec-8-en-10-one
showed 26 carbon signals, including a carbonyl (
d 197.5, C-3) and a
0
0
0
b
b
-
D-apiofuranosyl-(1 !6 )-
-D-glucopyranoside (2) (Fig. 1). This
quaternary carbon ( 35.2, C-1). These spectroscopic data indicates
d
study was conducted to find new agents with novel structure and
biological activities from the flower buds of L. japonica.
that 1 is a monocyclic sesquiterpene diglycoside.
The HMBC correlations (Fig. 1) between H-2 and C-3/C-6/C-14/
C-15; between H-6 and C-1/C-2/C-4/C-13/C-14; between H-4 and
C-3/C-13; between H-13 and C-5; and between H-14/H-15 and C-1/
C-2/C-6; together with their chemical shifts, indicated the
presence of 6-substituted 1,1,5-trimethylhex-4-en-3-one moiety.
2. Results
2
D
0
Compound 1: ½
a
ꢁ
+ 26.6 (c 0.04, MeOH), was obtained as a
1
1
white amorphous powder. The molecular formula of C26
H
40
O
11
The H – H COSY correlations of H-6/H-7/H-8 and H-10/H-11 and
the HMBC correlations between H-6 and C-8; between H-8 and C-
6
/C-9/C-10/C-12; between H-11 and C-9/C-10; between H-10 and
C-8/C-12; and between H-12 and C-8/C-9/C-10 showed the
presence of 11-oxygen substituted 9-methylpenta-7,9-dien-7-yl
*
Corresponding author.
E-mail address: hjgj85528@163.com (J. Han).
http://dx.doi.org/10.1016/j.phytol.2015.11.016
874-3900/ã 2015 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.
1

J.-R. Xu et al. / Phytochemistry Letters 15 (2016) 98–102
99
Fig. 1. Structure, key HMBC and 1H– H COSY correlations of compound 1.
1
side chain at C-6 of the hex-4-en-3-one moiety. Additionally, the
one methane (H-7), a tri-substituted double bond (H-9). 13C NMR
spectrum (Table 1) showed four quaternary carbons and a carbonyl
carbon (dC 208.6, C-10), The NMR spectrum also showed the signals
ascribable to the same diglycosyl moiety in 1. These spectroscopic
1
1
0
0
0
0
0
0
H– H COSY correlations of H-1 /H-2 /H-3 /H-4 /H-5 /H-6 and
their vicinal coupling constants, together with the HMBC
0
0
correlations between H-1 and C-11 and between H-11 and C-1 ,
indicated the connection of
b
-glucopyranosyloxy at C-11. The
data indicates that 2 is a tricyclic sesquiterpene
b
-
D
-apiofuranosyl-
1
1
00
00
00
0
b
H– H COSY correlation of H-1 /H-2 and the HMBC correlations
(1 !6 )-
-D-glucopyranoside, with an aglycone moiety different
from 1. In the H H COSY spectrum of 2 (Fig. 2), the correlations of
0
0
00
0
00
00
00
1 –1
between H-1 and C-4 /C-6 , between H-4 /H-5 and C-3 ,
0
00
between H-6 and C-1 , together with the quaternary nature of
C-3 , suggested a
00
0
b-apiofuranosyloxy at C-6 of the b-glucopyr-
Table 1
anosyl, which was supported by NMR data comparison of the
diglycosyl in 1 with structurally related compounds (Takayanagi
et al., 2003; Tamaki et al., 2000) and further confirmed by
enzymatic hydrolysis of 1 with snailase. In the hydrolysate of 1, a
sugar mixture of glucose and apiose was isolated by column
1
H NMR (500 MHz) and 13C NMR (150 MHz) spectral data of 1 and 2 (
d in ppm, J in
6
Hz, DMSO-d ).
Nos.
1
2
d
H
d
C
d
H
d
C
chromatography over silica gel (CH
identified by thin-layer liquid chromatography comparing with
authentic sugar controls. The sugar mixture, authentic -/ -glucose
and -/ -apiose separately reacted with -cycteine methyl ester and
arylisothiocyanate (Takana et al., 2007). The following HPLC
analysis indicated that two sugar derivatives from the mixture had
3
CN ꢀꢀ H
2
O, 7:2, v/v) and
1
2a
35.2
47.6
61.7
56.8
2.46 (1H, d, J = 16.5)
1.93 (1H, d, J = 16.5)
2b
3a
3b
4a
D
L
197.5 1.32 (1H, dd, J = 12.0, 6.0) 38.3
D
L
L
1.15 (1H, m)
5.85 (1H, s)
124.6 1.43 (1H, m)
1.33 (1H, m)
162.4 1.67 (1H, dd, J = 12.0, 6.0) 40.5
1.37 (1H, dd, J = 12.0, 6.0)
27.2
4b
5
5
6
7
8
9
a
b
the same retention time (t
derivatives, which indicated that both glycosyl units in 1 were the
-configuration. The similarity of the NMR data and the circular
dichroism spectra between 1 and the known acetylated
R
) to those of D-glucose and D-apiose
2.62 (1H, d, J = 9.5)
55.7
57.5
50.8
170.2
123.4
208.6
D
5.67 (1H, dd, J = 15.5, 9.5) 126.1 2.16 (1H, d, J = 5.0)
b
-D-
6.28 (1H, d, J = 15.5)
137.6
glucopyranoside (Lutz and Winterhalter,1992) indicated that 1 has
the same aglycone moiety including absolute configurations. The
configuration was further confirmed by comparison of the
experimental CD spectra of 1 with the calculated electronic CD
spectra, its aglycone, and a model compound with substitution of
the diglycosyl unit by a methyl group predicted from the quantum-
mechanical, time-dependent density functional theory (TDDFT)
calculations (Li et al., 2010). Therefore, the structure of compound
135.3 6.01 (1H, d, J = 0.5)
127.9
1
0
5.66 (1H, dd, J = 7.0, 6.5)
1
1a
4.33 (1H, dd, J = 12.5, 6.5) 64.2
4.14 (1H, dd, J = 12.5, 7.0)
2.08 (1H, dd, J = 12.0, 5.0) 47.5
1
1b
1.85 (1H, d, J = 12.0)
0.95 (3H, s)
0.93 (3H, s)
1
2
1.71 (3H, s)
1.87 (3H, s)
0.92 (3H, s)
0.85 (3H, s)
12.2
23.5
27.8
26.3
17.6
23.7
28.8
72.4
13
1
4
1.11 (3H, s)
1
5a
4.46 (1H, dd, J = 17.5, 2.0)
4.36 (1H, dd, J = 17.5, 2.0)
4.22 (1H, d, J = 8.0)
3.23 (1H, t, J = 8.0)
3.12 (1H, t, J = 8.0)
3.20 (1H, m)
3.30 (1H, m)
3.95 (1H, dd, J = 11.5, 2.0)
3.51 (1H, dd, J = 11.5, 6.0)
15b
0
0
0
0
0
1
2
3
4
5
4.16 (1H, d, J = 8.0)
2.91 (1H, t, J = 8.0)
3.28 (1H, dd, J = 9.0, 8.0)
2.93 (1H, t, J = 9.0)
3.15 (1H, t, J = 9.0)
3.80 (1H, d, J = 11.5)
3.46 (1H, dd, J = 11.5, 7.0)
4.82 (1H, d, J = 3.0)
3.71 (1H, d, J = 2.0)
101.4
73.7
76.1
70.5
75.2
67.3
104.7
78.5
75.4
71.1
78.8
68.2
1
was elucidated as (R)-dehydroxyabscisic alcohol
b
-
D
-apiofur-
0
0
0
b
anosyl-(1 !6 )-
993).
Compound 2: ½
white amorphous powder. The molecular formula C26
deduced from HR-ESI-MS. The IR spectrum of 2 showed the
-D-glucopyranoside (Lutz and Winterhalter,
1
2
0
aꢁ
ꢀ 45.9 (c 0.04, MeOH), was obtained as a
11 was
D
6’a
6 b
0
H
40
O
0
0
0
0
0
0
1
2
3
4
4
5
109.7 4.97 (1H, d, J = 2.5)
111.9
78.7
80.2
75.6
ꢀ1
75.5
78.5
73.7
3.81 (1H, d, J = 2.5)
presence of hydroxyl (3389 cm
) and conjugated carbonyl
ꢀ
1
1
(
1738 and 1643 cm ) groups. The H NMR spectrum (Table 1)
00
00
a
b
3.88 (1H, d, J = 9.0)
3.52 (1H, d, J = 9.0)
3.36 (1H, m)
3.83 (1H, d, J = 9.5)
3.63 (1H, d, J = 9.5)
3.55 (1H, s)
displayed signals including three methyls (H-12, H-13, H-14), five
methylenes (an oxygen-connecting) (H-3, H-4, H-5, H-11, H-15),
00
63.6
65.2

100
J.-R. Xu et al. / Phytochemistry Letters 15 (2016) 98–102
Fig. 2. Structure, key HMBC and 1H– H COSY correlations of compound 2.
1
H-3/H-4/H-5 and H-7/H-11, together with their chemical shifts and
coupling patterns, indicated that there were two vicinal coupling
aliphatic units in the aglycone moiety. In the HMBC spectrum,
correlations between H-13 and C-1/C-2/C-3/C-6 and between H-
3. Conclusions
We isolated and identified two new sesquiterpene glycosides
(R)-dehydroxyabscisic alcohol
0
0
0
b
b-D
-apiofuranosyl-(1 !6 )-
-D-
14 and C-2/C-5/C-6/C-7 showed connections of the C-2 with C-1/C-
glucopyranoside (1) and (ꢀ)-(1S,2R,6R,7R)-1,2,6-trimethyl-8-hy-
2
,6
3/C-6/C-13 and C-6 with C-2/C-5/C-7/C-14, which formed a 2,6-
droxy methyltricyclic[5.3.1.0 ]-undec-8-en-10-one -apiofur-
b-D
0
0
0
b
disubstituted 2,6-dimethyl five-membered ring. The HMBC
correlations between H-12 and C-1/C-2/C-10/C-11 indicated link-
ages between the C-1 with C-10/C-11/C-12, and further confirmed
the connection between the C-1 and C-2. In addition, the HMBC
correlations between H-7 and C-8/C-9/C-15; between H-9 and C-1/
C-7/C-15; between H-15 and C-8/C-9; together with the chemical
shifts, showed that both the methine (C-7) and the oxymethylene
anosyl-(1 !6 )-
-D-glucopyranoside (2), from the flower buds of
L. japonica. Compound 2 could significantly decrease monosodium
urate-mediated cytokine production from activated macrophage
through lowering IL-1
scientific clues to identify compound 2 as a potential new gout
prophylactic agent.
b and TNFa (Fig. 3). These results provided
(
C-15) were connected to one end (C-8) of the tri-substituted
4. Experimental
double bond and that C-1 was connected via the carbonyl (C-10) to
the other end (C-9), which constructed the 8-oxymethylene
cyclohexene ring fused with the latter five-membered ring to
give the tricyclic bridged structure of the aglycone in 2. The
4.1. General experimental procedure
Optical rotations were measured on P-2000 polarimeter
(JASCO, Tokyo, Japan). The UV spectrum was obtained using a
Shimadzu UV-2401-A spectrophotometer with PhotoMultiplier
Tube. IR spectra were recorded on a Nicolet 5700 FT-IR microscope
instrument (FT-IR microscope transmission) (Thermo Electron
Corporation, Madison, USA). The NMR spectra were recorded on a
Bruker AV-500 spectrometer, using TMS as an internal standard.
HR-ESI-MS spectra were measured on a Bruker UHR-TOF maXis
spectrometer. Column chromatography (CC) was performed with
silica gel (200–300 mesh, Qingdao Marine Chemical Inc., Qingdao,
China), Sephadex LH-20 (Pharmacia Biotech AB, Uppsala, Sweden),
CHP 20P (Mitsubishi Chemical Inc., Tokyo, Japan). HPLC was
performed on an Agilent 1100 apparatus equipped with a UV
detector and an YMC-Pack ODS-A (YMC, 1 ꢂ15 cm) column
(Agilent, USA).
0
0
0
b
presence of
b
-apiofuranosyl-(1 !6 )-
-glucopyranosyl was de-
1
1
duced by the similar H– H COSY and HMBC correlations to 1.
Additionally, the HMBC correlations between H-15 and C-1 and
between H-1 and C-15 indicated the diglycosyl at C-15 of the
0
0
aglycone. In the NOE spectrum, irradiation of H-11a enhanced H-
13 and H-14, indicating that the bridge methylene (C-11) and the
two methyl groups were oriented in the same direction. The
D
-
configuration was assigned for the two glycosyl units in 2
according to the same method described in 1. The CD spectrum
of 2 displayed a negative cotton effect at 335 nm (Deꢀ 2.36) for the
n ! p* transition of cyclohexanone chromophore, suggesting 2
possesses 1S,7R configuration according to the octant rule for
cyclohexenones (Snatzke, 1965), which was further confirmed by
comparison of the experimental CD spectrum of 2 with the
calculated ECD spectra and the aglycone methyl ether (model
compound). Thus, the structure of compound 2 was elucidated as
4.2. Plant material
(
[
ꢀ)-(1S,2R,6R,7R)-1,2,6-trimethyl-8-hydroxy
methyltricyclic
2
,6
00
0
b
The flower buds of L. japonica were collected in May 2014 from
Shangqiu, Henan Province, China, and authenticated by Prof. Li Ma
from Institute of Materia Medica. A voucher specimen (No.
5.3.1.0 ]-undec-8-en-10-one
b-
D
-apiofuranosyl-(1 !6 )-
-D-
glucopyranoside.

J.-R. Xu et al. / Phytochemistry Letters 15 (2016) 98–102
101
2
.3.2.1–Fr. 2.3.2.6. Fr. 2.3.2.4 (75 mg) was separated by reversed-
phase semi-preparative HPLC, using MeOH–H O (40:60, v/v) as the
mobile phase (1.5 mL/min, UV 254 nm), to yield 1 (1.2 mg,
= 25 min). Fr. 2.3.4 (3.5 g) was separated by CC over Sephadex
LH-20, eluted with petroleum ether–CHCl –MeOH (5:5:1, v/v/v), to
give Fr. 2.3.4.1–Fr. 2.3.4.5. Fr. 2.3.4.4 (85 mg) was separated by
reversed-phase (C18) semi-preparative HPLC, using MeOH–H
2
t
R
3
2
O
(
(
60:40, v/v) as the mobile phase (1.5 mL/min, UV 220 nm), to yield 2
1.8 mg, t = 26 min).
R
00
0
b
4
.4. (R)-dehydroxyabscisic alcohol
b
-D
-apiofuranosyl-(1 !6 )-
-D-
glucopyranoside (1)
2
0
White amorphous powder; ½
aꢁ
+ 26.6 (c 0.04, MeOH); UV
D
(
MeOH) lmax (log e) 239 (5.68), 341 (4.73) nm; CD (MeOH) 225
(
3
Deꢀ 25.5), 262 (De+ 40.6), 328 (Deꢀ 2.81) nm; IR
nmax 3387,
ꢀ1
1
13
022, 2845,1637, 1425,1369,1252,1049, 825, 652 cm ; H and
C
+
NMR data see Table 1. HR-ESI-MS m/z: 551.2469 [M + Na] (Calcd.
for C26 11Na, 551.2461).
40
H O
4
.5. (ꢀ)-(1S,2R,6R,7R)-1,2,6-trimethyl-8-hydroxy methyltricyclic
2,6
00
0
b
[5.3.1.0 ]-undec-8-en-10-one
b-
D
-apiofuranosyl-(1 !6 )-
-D-
glucopyranoside (2)
2
0
White amorphous powder; ½
MeOH) max(log ) 209 (4.73), 231 (4.52) nm; CD (MeOH) 231
De+ 0.65), 335 (Deꢀ 2.36) nm; IR max 3389, 3015, 2917, 1738,
643, 1473, 1335, 1172, 923, 825, 552 cm ; H and C NMR data
see Table 1. HR-ESI-MS m/z: 529.2631 [M + H]+ (Calcd. for
11, 529.2640).
aꢁ
ꢀ 45.9 (c 0.04, MeOH); UV
D
(
(
1
l
e
n
ꢀ1
1
13
26 41
C H O
4
.6. Cell culture and treatment
Human monocytic cell line, THP-1 (ATCC TIB-202), purchased
from Shanghai Cell Bank (Shanghai, China), was grown in RPMI
640 with HEPES, supplemented with 10% FBS and penicillin/
1
streptomycin. Cells were induced to differentiate into mature
macrophages using 12-O-tetradecanoylphorbol-13-acetate (Enzo
Life Sciences) at a concentration of 0.5 mM for 3 h. After induction,
cells were washed with PBS and then plated into 12-well tissue
Fig. 3. Compound 2 inhibited MSU induced cytokine production. THP-1 macro-
phages were pretreated with different concentrations of compounds for 4 h
followed by stimulation with MSU (10 mg/dL) for 24 h. Media were analyzed for IL-
5
culture plates at a density of 6 ꢂ10 cells/well and incubated
overnight. Prior to any activation studies, cells were washed with
PBS followed by the addition of 0.5 mL of serum-free Opti-MEM per
well (Orlowsky et al., 2014).
1
b
and TNF
a
production by ELISA. Values were expressed as mean ꢃ SD (n = 3).
#
#
P < 0.01 vs Control group; *P < 0.05, **P < 0.01 vs MSU group.
2
0140522) was deposited at the Department of Rheumatology and
4
.7. Inhibition studies
Immunology, Shanghai East Hospital, Tongji University School of
Medicine (Shanghai, China).
To test for anti-inflammatory effects of compounds, macro-
phages were pretreated with different concentrations of com-
pounds for 4 h prior to the addition of monosodium urate (MSU)
4.3. Extraction and isolation
crystals (10 mg/dL). Culture media were collected at 24 h and IL-1
and TNF concentrations were analyzed by ELISA. The IL-1 and
TNF data were from 4 separate experiments (Orlowsky et al.,
014).
b
The dried flower buds of L. japonica (45 kg) were extracted with
a
b
H
2
O (120 L, 3 ꢂ1 h). The aqueous extracts were evaporated under
reduced pressure to yield a brown residue (22 kg). The residue was
then dissolved in H O (100 L), loaded on a macroporous adsorbent
resin (HPD-110, 20 L) column (20 cm ꢂ 200 cm), and eluted
successively with H O (50 L), 60% EtOH (100 L), and 95% EtOH
80 L) to yield three fractions (Fr. 1–Fr. 3). Fr. 2 (280 g) was
chromatographed over MCI gel CHP 20P, eluting successively with
O (20 L), 40% EtOH (30 L), 60% EtOH (30 L), and 95% EtOH (10 L),
a
2
2
Acknowledgment
2
(
This research was supported by the Leading Talent Project of
Shanghai Pudong New Area (PDZYXK-4-2014001).
H
2
to give five fractions (Fr. 2.1–Fr. 2.5). Fr. 2.3 (26 g) was subjected to
CC over silica gel, with elution by a gradient of increasing acetone
References
(
2
0–100%) in petroleum ether, to yield subfractions Fr. 2.3.1–Fr.
.3.5. Fr. 2.3.2 (4.1 g) was separated by CC over Sephadex LH-20,
eluted with petroleum ether–CHCl –MeOH (5:5:2, /v/v), to give Fr.
Bi, Y.F., Tian, Y., Pei, S.S., Liu, H.M., 2008. Secoiridoid glycosides from Flos Lonicerae.
Chin. Tradit. Herb Drugs 39, 18–21.
Jiang, N.H., 2015. Study on chemical constituents of Lonicera japonica bud. Zhong
Yao Cai 38, 315–317.
3
v

102
J.-R. Xu et al. / Phytochemistry Letters 15 (2016) 98–102
Kakuda, R., Imai, M., Yaoita, Y., Machida, K., Kikuchi, M., 2000. Secoiridoid glycosides
from the flower buds of Lonicera japonica. Phytochemistry 55, 879–881.
Kumar, N., Singh, B., Bhandari, P., Gupta, A.P., Uniyal, S.K., Kaul, V.K., 2005.
Biflavonoids from Lonicera japonica. Phytochemistry 66, 2740–2744.
Kumar, N., Singh, B., Gupta, A.P., Kaul, V.K., 2006. Lonijaposides, novel cerebrosides
from Lonicera japonica. Tetrahedron 62, 4317–4322.
Li, X.C., Ferreira, D., Ding, Y.Q., 2010. Determination of absolute configuration of
natural products: theoretical calculation of electronic circular dichroism as a
tool. Curr. Org. Chem. 14, 1678–1697.
Lin, L.M., Zhang, X.G., Zhu, J.J., Gao, H.M., Wang, Z.M., Wang, W.H., 2008. Two new
triterpenoid saponins from the flowers and buds of Lonicera japonica. J. Asian
Nat. Prod. Res. 10, 925–929.
Lutz, A., Winterhalter, P., 1992. Isolation of additional carotenoid metabolites from
quince fruit (Cydonia oblonga Mill.). J. Agric. Food Chem. 40, 1116–1120.
Lutz, A., Winterhalter, P., 1993. Abscisic alcohol glucoside in quince. Phytochemistry
Snatzke, G., 1965. Circulardichroismus-VIII, modifizierung der octantenregel für
-ungesättigt ketone: theorie. Tetrahedron 21, 413–419.
a,
b
Takana, T., Nakashima, T., Ueda, T., Tomi, K., Kouno, I., 2007. Facile discrimination of
aldose enantiomers by reversed-phase HPLC. Chem. Pharm. Bull. 55, 899–901.
Takayanagi, T., Ishikawa, T., Kitajima, J., 2003. Sesquiterpene lactone glucosides and
alkyl glycosides from the fruit of cumin. Phytochemistry 63, 479–484.
Tamaki, A., Ide, T., Otsuka, H., 2000. Phenolic glycosides from the leaves of Alangium
platanifolium var. platanifolium. J. Nat. Prod. 63, 1417–1419.
Teng, R.W., Wang, D.Z., Chen, C.X., 2000. Two triterpenoid saponins from Lonicera
Japonica. Chin. Chem. Lett. 11, 337–340.
Tzeng, T.F., Tzeng, Y.C., Cheng, Y.J., Liou, S.S., Liu, I.M., 2015. The ethanol extract from
Lonicera japonica Thunb. Regresses nonalcoholic steatohepatitis in a
methionine- and choline-deficient diet-fed animal model. Nutrients 7, 8670–
8684.
Yu, D.Q., Chen, R.Y., Huang, L.J., Xie, F.Z., Ming, D.S., Zhou, K., 2008. The structure and
absolute configuration of Shuangkangsu: a novel natural cyclic peroxide from
Lonicera japonica (Thunb.). J. Asian Nat. Prod. Res. 10, 851–856.
Yu, Y., Jiang, Z., Song, W., Yang, Y., Li, Y., Jiang, J., Shi, J.G., 2015. Glucosylated
caffeoylquinic acid derivatives from the flower buds of Lonicera japonica. Acta
Pharm. Sin. B 5, 210–214.
3
2, 57–60.
Ni, F.Y., Liu, L., Song, Y.L., Wang, X.J., Zhao, Y.W., Huang, W.Z., Wang, Z.Z., Xiao, W.,
015. Anti-complementary phenolic acids from Lonicera japonica. Zhongguo
2
Zhong Yao Za Zhi 40, 269–274.
Orlowsky, E.W., Stabler, T.V., Montell, E., Vergés, J., Kraus, V.B., 2014. Monosodium
urate crystal induced macrophage inflammation is attenuated by chondroitin
sulphate: pre-clinical model for gout prophylaxis? BMC Musculoskelet. Disord.
Zheng, Z.F., Zhang, Q.J., Y, 2012. Four new N-contained iridoid glycosides from flower
buds of Lonicera japonicanew. J. Asian Nat. Prod. Res. 14, 729–737.
15, 318.