New sesquiterpenoid glycoside from the rhizomes of Atractylodes lancea

Article abstract of DOI:10.1080/14786419.2018.1553170

Six sesquiterpenoids and four lignans (1–10) were isolated from the n-BuOH extract of the rhizomes of Atractylodes lancea. Among them, the new sesquiterpenoid glycoside named (4 R, 5S, 7R)-hinesolone-11-O-β-?-glucopyranoside (1), along with three known co

Full text of DOI:10.1080/14786419.2018.1553170

Natural Product Research
Formerly Natural Product Letters
ISSN: 1478-6419 (Print) 1478-6427 (Online) Journal homepage: http://www.tandfonline.com/loi/gnpl20
New sesquiterpenoid glycoside from the rhizomes
of Atractylodes lancea
Liping Long, Lushan Wang, Shizhou Qi, Yiren Yang & Huiyuan Gao
To cite this article: Liping Long, Lushan Wang, Shizhou Qi, Yiren Yang & Huiyuan Gao (2019):
New sesquiterpenoid glycoside from the rhizomes of Atractylodesꢀlancea, Natural Product
Research, DOI: 10.1080/14786419.2018.1553170
To link to this article: https://doi.org/10.1080/14786419.2018.1553170
View supplementary material
Published online: 08 Jan 2019.
Submit your article to this journal
Article views: 11
View Crossmark data
Full Terms & Conditions of access and use can be found at
http://www.tandfonline.com/action/journalInformation?journalCode=gnpl20

NATURAL PRODUCT RESEARCH
https://doi.org/10.1080/14786419.2018.1553170
New sesquiterpenoid glycoside from the rhizomes of
Atractylodes lancea
Liping Long, Lushan Wang, Shizhou Qi, Yiren Yang and Huiyuan Gao
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang,
People’s Republic of China
ABSTRACT
ARTICLE HISTORY
Six sesquiterpenoids and four lignans (1–10) were isolated from
the n-BuOH extract of the rhizomes of Atractylodes lancea. Among
them, the new sesquiterpenoid glycoside named (4 R, 5S, 7R)-
hinesolone-11-O-b-ᴅ-glucopyranoside (1), along with three known
compounds (2–4) were first obtained from this genus. All the iso-
lates were elucidated by spectroscopic analyses and chemical
methods, and the absolute configurations were assigned by elec-
tronic circular dichroism spectroscopy technique. In addition, the
cytotoxic bioassay of compound 1 was evaluated and results
showed it had no significant antitumor activity against human
cancer cell lines MCF-7, HepG-2 and Hela.
Received 2 September 2018
Accepted 25 November 2018
KEYWORDS
Atractylodes lancea;
rhizomes; sesquiterpenoids;
lignans; absolute
configuration
1. Introduction
Atractylodes lancea (Thunb.) DC. (Compositae), which called “Cangzhu” in China, is a
perennial herb distributed widely in eastern Asia. As a traditional medicine listed in
the Chinese pharmacopoeias, A. lancea was used to treat rheumatic disease, functional
dyspepsia, gastroparesis, night blindness as well as influenza (Endo et al. 1979; Sakurai
CONTACT Huiyuan Gao
sypugaohy@163.com
School of Traditional Chinese Materia Medica, Shenyang
Pharmaceutical University, Shenyang, 110016, People’s Republic of China
Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2018.1553170.
ß 2018 Informa UK Limited, trading as Taylor & Francis Group

2
L. LONG ET AL.
Figure 1. Structures of compounds 1–10.
et al. 1994; Resch et al. 1998; Nakai et al. 2003). Published articles have reported that
a number of components, mainly sesquiterpenoids, polyacelenes, phenylpropanoids,
phenolic acids and steroids were isolated from A. lancea (Duan et al. 2008; Deng et al.
2
016; Li et al. 2017). And some compounds showed diverse and promising biological
properties such as anti-inflammatory (Chae et al. 2016; Dong et al. 2008; Hoang et al.
016; Xu et al. 2018; Yin et al. 2015), insecticide (Chen et al. 2015), hepatoprotection
Xu et al. 2016c) and anti-tumor (Wang et al. 2008). Previous studies showed the n-
BuOH part of an aqueous EtOH extract of A. lancea have significant hepatoprotection
Xu et al. 2016c). For further search for the biological active compounds from A. lan-
2
(
(
cea, n-BuOH part was investigated. And ten compounds (1–10) were isolated using
various column chromatographic methods. Among those isolates, a novel sesquiterpe-
noid glycoside (1) and three known compounds (2–4) were first isolated from this
genus (Figure 1). Their structures were established by 1D and 2D NMR spectroscopic
and physico-chemical analyses. The absolute configurations of 1 were deduced by
comparison of the experimental and calculated electronic circular dichroism (ECD). The
antitumor effect of compound 1 on human breast cancer cell line (MCF-7), human

NATURAL PRODUCT RESEARCH
3
hepatoma cell line (HepG-2) and human cervical cancer cell line (Hela) was
also studied.
2. Results and discussion
Compound 1 was obtained as pale yellow oil, which exhibited a positive HRESIMS
þ
quasi-molecular ion at m/z 399.2387 [M þ H] (calcd for C H O , 399.2383), compat-
21 35 7
ible with the molecular formula of C H O (X ¼ 5). Its IR (KBr) absorption signals
21
34 7
ꢀ
1
ꢀ1
were attributed to hydroxyl (3411 cm ), carbonyl (1631 cm ) and olefinic bond
ꢀ
1
1
13
(
1616 cm ). The H and C NMR analyses (Figures S4–S5, Supplemental Material)
1
indicated 20 and 21 resonance signals, respectively. The H NMR spectrum of 1,
revealed four methyl groups at dH 1.33 (3 H, s), dH 1.33 (3 H, s), dH 1.09 (3 H, d,
J ¼ 6.8 Hz) and d 2.08 (3 H, s), one olefinic proton at d 5.77 (1 H, s), and the proton
H
H
signals of one sugar unit at d 4.54 (1 H, d, J ¼ 7.7 Hz) and 3.18–3.86 (6 H, m).
H
13
Furthermore, according to the C NMR, DEPT and HSQC data, four methyl carbons at
d 16.7, 21.3, 24.8 and 26.2, a pair of olefinic carbons at d 125.9 and 173.0, one car-
C
C
bonyl carbon at d 202.3, one oxygenated quaternary carbon at d 79.4, one quater-
C
C
nary carbon at d 51.7, two methenyl carbons at d 38.5 and 52.3, four methylene
C
C
carbons at d 28.7, 32.5, 35.9 and 43.5, and carbons of sugar unit at d 98.6, 78.5, 77.6,
C
C
75.4, 71.8 and 62.8 were clearly assigned. Combined with 1D NMR data, the key HMBC
correlations (Figure S1, Supplemental Material) of H-1 to C-3, 5 and 15, H-3 to C-2, 4
and 5 indicated the presence of cyclohexanone. And the isopropyl group was con-
firmed to be located at C-7 by the HMBC correlations of H-12 to C-7 and 11, H-13 to
C-7 and 11. These spectroscopic data suggested that 1 possess an aglycone similar to
the known compound named 2-oxo-12-hydroxy-hinesol (Kamauchi et al. 2015). And
the difference between aglycone of 1 and 2-oxo-12-hydroxy-hinesol was the absence
of a hydroxyl group that linked to C-12. Based on the above data, the structure of 1
was established. In addition, the experiment of enzyme hydrolysis showed the exist-
ence of ᴅ-glucose unit, and the b-configuration of glucose was deduced based on the
J1
0
,2
0
value (7.7 Hz). A key long-range HMBC correlation of the anomeric proton at dH
0
4
.54 (Glc-H-1 ) to the quaternary carbon at d 79.4 (C-11) defined the location of glu-
C
cose moiety. Consequently, the planar structure of 1 was identified as hinesolone-11-
O-b-ᴅ-glucopyranoside.
Moreover, the stereochemistry of 1 was elucidated on the basis of its ROESY and
ECD spectrum data (Figure S2, Supplemental Material). In the CD spectrum, the nega-
tive Cotton effect at 243 nm indicated that the absolute configuration of C-7 was R
(
7
Gawro nꢀ ski 1982; Xu et al. 2016c). Furtherly, the absolute stereochemistry at the C-4, 5,
positions in 1 were determined to be 4 R, 5S, 7 R. Consequently, the structure of
compound 1 was identified as (4 R, 5S, 7R)-hinesolone-11-O-b-ᴅ-glucopyranoside.
Compounds 2–3 were obtained as white amorphous powder, their planar structures
0
0
0
0
both were defined as 4, 7, 9, 3 , 9 -pentahydroxy-3-methoxyl-8-4 -oxyneolignan-3 -O-
b-ᴅ -glucopyranoside by comparing their NMR data to those data which previously
reported (Gan et al. 2008; Yang et al. 2012). The erythro configuration of compounds
2
-3 were determined by the J7,8 value (5.5, 5.0 Hz). And the configuration (8S) of 2
was confirmed by the positive Cotton effect at 233 nm in CD spectrum (Yang et al.

4
L. LONG ET AL.
2
012). Similarly, the configuration of compound 3 was elucidated as 8 R. Thus, their
0
0
0
structures were identified as (7 R, 8S)-4, 7, 9, 3 , 9 -pentahydroxy-3-methoxyl-8-4 -oxy-
neolignan-3 -O-b-ᴅ -glucopyranoside (2) and (7S, 8R)-4, 7, 9, 3 , 9 -pentahydroxy-3-
methoxyl-8-4 -oxyneolignan-3 -O-b-ᴅ-glucopyranoside (3).
0
0
0
0
0
In addition, the other five sesquiterpenoids and two lignan known compounds
0
were isolated and identified as syringaresinol-4 -O-b-ᴅ-glucopyranoside (4) (Wang and
Yu 1998), (5 R, 7 R, 10S)-11-hydroxyeudesm-3-en-2-one-11-O-b-ᴅ -glucopyranoside (5)
(Kitajima et al. 2003), atractylosides I (6) (Yahara et al. 1989), (5 R, 7 R, 10S)-isopterocar-
polone-11-O-b-ᴅ-apiofuranosyl-(1!6)-b-ᴅ-glucopyranoside (7) (Xu et al. 2016b), (7R)-3,
4
2
-dehydrohinesolone-11-O-b-ᴅ-glucopyranoside (8) (Xu et al. 2016a), (3 R, 4S, 7 R, 10R)-
-hydroxypancherione-11-O-b-ᴅ-glucopyranoside (9) (Xu et al. 2016a), and secoisolari-
ciresin-4-yl-O-b-ᴅ-glucopyranoside (10) (Buske et al. 2001) by comparison of their phys-
ical and spectroscopic data to those reported in the references.
3. Experimental
3.1. General experimental procedures
Optical rotations were measured on an Anton-Paar MCP 200 Polarimeter. IR spectrum
were recorded on Bruker IFS-55 and PerkinElmer 100 infrared spectrophotometer with
KBr disks. The ESI-MS analyzes were achieved on 6540 UHD accurate mass Q-TOF mass
1
13
spectrometer. H and C NMR spectrum data were recorded on Bruker ARX 400 and
00 NMR spectrometer with TMS as internal standard. Chemical shifts were given in
6
ppm (d). An analytical HPLC chromatography was carried on DGU-20A3 (Kyoto, Japan),
LC-20AB detector and an analytical reversed phase C18 column (4.6 ꢁ 250 mm, 5 lm,
Dikma Technologies, China). A preparative RP-HPLC was performed on an Agela HP-Q-
P050 (Tianjin, China), the detector was HP-Q-UV 100 (Tianjin, China) and a preparative
C18 column (20 ꢁ 250 mm, 5 lm, Ryoung Tech Led, Tianjin, China). A semi-preparative
HPLC chromatography was equipped with LC-20AR (Kyoto, Japan), SPD-20A detector
(
Kyoto, Japan) and a C18 column (10 ꢁ 250 mm, 5 lm, Ryoung Tech Led, Tianjin,
China). Macroporous adsorption resin D101 (Langfang Nanda resin Co., Ltd.). Silica gel
100-200 and 200-300 mesh, Qingdao Marine Chemical Co., Ltd., Qingdao, China).
Sephadex LH-20 (Pharmacia Biotech, USA).
(
3
.2. Plant material
The dried rhizomes of Atractylodes lancea were collected in May 2016 from Jurong city
Jiangsu province, China) and identified by Associate Prof. Jiu-Zhi Yuan of Shenyang
(
Pharmaceutical University. A voucher specimen (CZ-16-XS002A) was deposited in the
Department of Natural Products Chemistry, Shenyang Pharmaceutical University,
Shenyang, China.
3.3. Extraction and isolation
The dried rhizomes of A. lancea (16 Kg) were crushed and extracted thrice with 75%
EtOH for 2 h under refluxing. After evaporating the solvent, the extracts were

NATURAL PRODUCT RESEARCH
5
suspended in water with a ratio of 1:1, and partitioned with petroleum ether, EtOAc,
and n-BuOH (1:1, three times), successively. The n-BuOH extract (301 g) was further
fractioned by D101 macroporous resin column chromatography, eluted with a step
gradient of EtOH/H O (v/v), to yield Fr. A (67 g, 10% EtOH-H O), Fr. B (16 g, 30% EtOH-
2
2
H O), Fr. C (28 g, 50% EtOH-H O), Fr. D (18 g, 70% EtOH-H O), Fr. E (4 g, 100% EtOH-
2
2
2
H O). Fraction D was further fractioned by silica gel column eluted with CH Cl /CH OH
2
2
2
3
to give Fr. D1-D2. Through employed with HPLC (eluted with 30% MeOH-H O), com-
2
pound 4 (11.5 mg) and 1 (13.0 mg) were acquired from Fr. D1 and D2, respectively.
Fraction C was further separated by silica gel column, eluted with CH Cl /CH OH to
2
2
3
obtain Fr. C1-C10. Fraction C5 was separated by an Sephadex LH-20 column to get
subfractions. Then these subfractions were further separated by HPLC, eluted with
MeOH-H O 40% (v/v, flow rate 8 ml/min) to give compound 7 (3.5 mg). Fraction C4, C8
2
and C9 were further chromatographed on HPLC eluted with CH CN–H O 17%, 8% and
3
2
CH OH–H O 30%, respectively, to give compounds 6 (50.0 mg), 2 (6.0 mg), 3 (5.0 mg)
3
2
and 9 (10.0 mg). Fr. C3 was carried on Sephadex LH-20 column and HPLC (eluted with
MeOH-H O 45%), successively, to obtain compound 5 (5.0 mg). Fr. C7 was separated
2
by silica gel column (eluted with CH Cl /CH OH) to fragment into subfractions, then
2
2
3
Fr. C7.1 and C7.3 was chromatographed by HPLC eluted with CH OH-H O 35% and
3
2
20%, respectively, to give compounds 8 (13.0 mg) and 10 (2.3 mg).
3
.3.1. (4 R, 5S, 7R)-hinesolone-11-O-b-ᴅ-glucopyranoside (1)
Pale yellow oil; IR (KBr) m : 3411, 2967, 2923, 2859, 1631, 1616, 1383, 1054,
max
ꢀ
1
þ
1
1
(
032 cm ; HRESIMS: m/z 399.2378 [M þ H] (calcd for C H O , 399.2378). H NMR
21 35 7
0
400 MHz, CD OD): d 5.77 (1 H, s, H-1), 4.54 (1 H, d, 7.7 Hz, H-Glc-1 ), 3.18-3.86 (6 H, m),
3 H
2
2
.46 (1 H, dd, 16.8, 4.6 Hz, H-3b), 2.28 (1 H, dd, 16.8, 9.8 Hz, H-3a), 2.22 (1 H, m, H-7),
.18 (1 H, m, H-4), 2.08 (3 H, d, 0.6 Hz, H-15), 2.01 (1 H, dd, 13.6, 7.3 Hz, H-9b), 1.90 (2 H,
m, H-8), 1.89 (2 H, m, H-6), 1.70 (1 H, m, H-9a), 1.33 (3 H, s, H-12), 1.33 (3 H, s, H-13),
1
3
1
1
4
1
.09 (3 H, d, 6.8 Hz, H-14). C NMR (100 MHz, CD OD): d 202.3 (C-2), 173.0 (C-10),
3 C
0
25.9 (C-1), 98.6 (C-Glc-1 ), 79.4 (C-11), 78.5, 77.6, 75.4, 71.8, 62.8, 52.3 (C-7), 51.7 (C-5),
3.5 (C-3), 38.5 (C-4), 35.9 (C-6), 32.5 (C-9), 28.7 (C-8), 26.2 (C-13), 24.8 (C-12), 21.3 (C-
5), 16.7 (C-14).
0
0
0
0
3
.3.2. (7 R, 8S)-4, 7, 9, 3 , 9 -pentahydroxy-3-methoxyl-8-4 -oxyneolignan-3 -O-
b-ᴅ-glucopy-ranoside (2)
White amorphous powder; H-NMR data (CD OD, 600 MHz): d 7.11 (1 H, d, 1.5 Hz, H-
1
3
H
0
0
2
6
(
), 7.06 (1 H, d, 1.5 Hz, H-2), 6.90 (1 H, dd, 8.1, 1.5 Hz, H-6), 6.85 (1 H, d, 8.2 Hz, H-5 ),
0
.82 (1 H, dd, 8.2, 1.5 Hz, H-6 ), 6.80 (1 H, d, 8.1 Hz, H-5), 4.91 (1 H, d, 5.5 Hz, H-7), 4.84
1 H, d, 7.6 Hz, H-Glc-1 ), 4.38 (1 H, m, H-8), 3.93 (1 H, m, H-9a), 3.86 (3 H, s, H-OCH ),
0
3
0
3
7
.79 (1 H, dd, 12.0, 3.0 Hz, H-9b), 3.59 (2 H, t, H-9 ), 3.39-3.52 (6 H, m), 2.64 (2 H, t,
.3 Hz, H-7 ), 1.84 (1 H, m, 8 ); C-NMR data (CD OD, 150 MHz): d 149.7 (C-3 ), 148.8
0
0
0
13
0
3
C
0
0
(
(
7
C-3), 147.9 (C-4), 147.0 (C-4 ), 138.3 (C-1 ), 134.2 (C-1), 124.4 (C-6 ), 120.9 (C-6), 120.4
C-2 ), 120.2 (C-5 ), 115.9 (C-2), 111.7 (C-5), 103.7 (C-Glc-1 ), 87.1 (C-8), 78.2;77.9, 75.1,
0 0 0
3.4 (C-7), 71.5, 62.6, 62.2 (C-9 ), 61.6 (C-9), 56.5 (C-OCH ), 35.3 (C-8 ), 32.4 (C-7 ).
3
0
0
0

6
L. LONG ET AL.
0
0
0
3
3
.3.3. (7S, 8R)-4, 7, 9, 3 , 9 -pentahydroxy-3-methoxyl-8-4 -oxyneolignan-
0
-O-b-ᴅ-glucopy-ranoside (3)
White amorphous powder; H-NMR data (CD OD, 600 MHz): d 7.09 (1 H, d, 1.6 Hz, H-
), 6.99 (1 H, d, 1.3 Hz, H-2), 6.87 (1 H, d, 8.2 Hz, H-5 ), 6.84 (1 H, dd, 8.1, 1.3 Hz, H-6),
.80 (1 H, dd, 8.2, 1.6 Hz, H-6 ), 6.76 (1 H, d, 8.1 Hz, H-5), 4.92 (1 H, d, 5.0 Hz, H-7), 4.90
1 H, d, 7.6 Hz, H-Glc-1 ), 4.28 (1 H, m, H-8), 3.92 (1 H, m, H-9a), 3.83 (3 H, s, H-OCH ),
.73 (1 H, m, H-9b), 3.56 (2 H, t, H-9 ), 3.41-3.90 (6 H, m); 2.60 (2 H, t, 7.3 Hz, H-7 ), 1.81
1 H, m, H-8 ), C-NMR data (CD OD, 150 MHz): d 150.0 (C-3 ), 148.8 (C-3), 147.9 (C-4 ),
47.0 (C-4), 138.4 (C-1 ), 134.0 (C-1), 124.2 (C-6 ), 121.4 (C-6), 120.5 (C-2 ), 119.2 (C-5 ),
1
3
H
0
0
2
6
0
0
(
3
(
1
1
6
3
0
0
0
13
0
0
0
3
C
0
0
0
0
15.9 (C-2), 111.5 (C-5), 103.6 (C-Glc-1 ), 87.8 (C-8), 78.3, 77.9, 75.1, 73.7 (C-7), 71.5,
2.6, 62.2 (C-9 ), 61.6 (C-9), 56.5 (C-OCH ), 35.4 (C-8 ), 32.5 (C-7 ).
0
0
0
3
0
3
.3.4. Syringaresinol-4 -O-b-ᴅ-glucopyranoside (4)
1
0
0
Yellow amorphous powder; H-NMR data (CD OD, 600 MHz): d 6.76 (2 H, s, H-2 , 6 ),
.70 (2 H, s, H-2, 6), 4.81 (1 H, d, 3.2 Hz, H-7 ), 4.76 (1 H, d, 3.5 Hz, H-7), 4.34 (2 H, m, H-
a, 9a), 3.96 (2 H, m, H-9b, 9 b), 3.90 (6 H, s, 3 , 5 -OCH ), 3.88 (6 H, s, 3, 5-OCH ), 3.24-
.81 (6 H, m), 3.17 (2 H, m, H-8, 8 ); C-NMR data (CD OD, 150 MHz): d 154.4 (C-3 , 5 ),
49.4 (C-3, 5), 139.6 (C-1 ), 135.6 (C-4, 4 ), 133.0 (C-1), 105.4 (C-2 , 6 ), 104.9 (C-2, 6),
04.6 (C-Glc-1 ), 87.6 (C-7 ), 87.2 (C-7), 78.3, 77.8, 75.7, 72.9 (C-9, 9 ), 71.3, 62.6, 57.1 (5 -
OCH ), 56.8 (3 -OCH ), 55.7 (C-8), 55.7 (5-OCH ), 55.5 (C-8 ), 55.5 (3-OCH ).
3
H
0
6
9
3
1
1
0
0
0
0
3
3
0
13
0
0
3
C
0
0
0
0
0
0
0
0
0
0
3
3
3
3
3.4. Enzyme hydrolysis
The compound 1 was hydrolyzed by glusulase to obtain 1a, which was used for the
monosaccharide determination, and the glusulase can hydrolyze glycoside containing
b- bond only. Briefly, weigh the sample (4 mg) and enzyme (8 mg) exactly to be dis-
solved in water (4 ml), and heated for 24 hours in water bath under constant tempera-
ꢂ
ture 37 C. The reaction mixture was extracted with ethyl acetate several times to
make sure the monosaccharides and aglycone were separated, and the aqueous layer
dried by evaporation in vacuum. Eventually, the monosaccharide residues were identi-
fied by HPLC analyses using an Asahipak NH P-50 4E column and an optical rotation
2
detector (JASCO ORD-4090), eluted with acetonitrile-water (75:25, v/v); flow rate:
1.0 mL/min. ᴅ -glucose was confirmed by comparison of the retention time with
authentic sample, the retention time of ᴅ-glucose was about 8.3 minutes under the
ꢂ
temperature of 30 C.
3.5. Cytotoxicity test
Anticancer activity of compound 1 was examined against several cell lines, including
MCF-7, HepG-2 and Hela, and was determined by an MTT assay. Briefly, the cell lines
were seeded into each well of the 96-microwell and allowed to adhere for 24 h. After
removal of medium, fresh medium containing different concentration of compound 1
was added to each well. The compound 1 were dissolved in DMSO to reach the con-
centration of 100 mM, then further diluted with medium to 200 lM. Furthermore, the
samples were orderly added to well by 1:1 gradient dilution to obtain several samples

NATURAL PRODUCT RESEARCH
7
with different concentration from 100 lM to 0.4 lM. After 24 h cultured, 5% MTT solu-
tion was added to each well, and reaction time was about 4 h. The OD value of each
well was tested by spectrophotometry at 570 nm wavelength. The experiment was
repeated three times.
Â
Ã
Cell death ð%Þ ¼ A570ðnegative controlÞ ꢀ A570ðtestÞ =½A570ðnegative controlÞ
ꢀ
A570ðpositive controlÞꢃꢁ100%
4. Conclusion
The phytochemistry of the n-BuOH extract from the rhizomes of Atractylodes lancea
was investigated to yield six sesquiterpenoids and four lignans, containing the new
spirovetivane-type sesquiterpenoid glycoside (1) and three known compounds (2–4)
which were obtained from the genus Atractylodes for the first time. Their structures
were elucidated on the basis of physical and spectroscopic data analyses. MTT assay
was used to study antitumor activity on MCF-7, HepG-2 and Hela, and compound 1
showed no significant antitumor activity on these three cell lines and the IC50 values
of these three cancer cell lines were more than 100 lM.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by the National Natural Science Foundation of China [grant numbers
8
1573601], Youth Teacher Development Support scheme of Shenyang Pharmaceutical University
(2014) and the Project of Key Laboratory of Structure-Based Drug Design & Discovery of Ministry
of Education of Shenyang Pharmaceutical University.
References
Buske A, Schmidt J, Porzel A, Adam G. 2001. Alkaloidal, megastigmane and lignan glucosides
from Antidesma membranaceum (Euphorbiaceae). Eur J Org Chem. 2001(18):3537–3543.
Chae HS, Kim YM, Chin YW. 2016. Atractylodin inhibits interleukin-6 by blocking NPM-ALK acti-
vation and MAPKs in HMC-1. Molecules. 21(9):1169.
Chen HP, Zheng LS, Yang K, Ning L, Geng ZF, Ma P, Cai Q, Du SS, Deng ZW. 2015. Insecticidal
and repellant activities of polyacetylenes and lactones derived from Atractylodes lancea
rhizomes. Chem Biodivers. 12(4):593–598.
Deng AP, Li Y, Wu ZT, Liu T, Kang LP, Nan TG, Zhan ZL, Guo LP. 2016. Advances in studies on
chemical compositions of Atractylodes lancea and their biological activities. Chin J Chin Mater
Med. 41(21):3904–3913.
Dong HY, He LC, Huang M, Dong YL. 2008. Anti-inflammatory components isolated from
Atractylodes macrocephala Koidz. Nat Prod Res. 22(16):1418–1427.
Duan JA, Wang LY, Qian SH, Su SL, Tang YP. 2008. A new cytotoxic prenylated dihydrobenzo-
furan derivative and other chemical constituents from the rhizomes of Atractylodes lancea DC.
Arch Pharm Res. 31(8):965–969.
Endo K, Taguchi T, Taguchi F, Hikino H, Yamahara J, Fujimura H. 1979. Antiinflammatory princi-
ples of Atractylodes rhizomes. Chem Pharm Bull. 27(12):2954–2958.

8
L. LONG ET AL.
Gan ML, Zhang YL, Lin S, Liu MT, Song WX, Zi JC, Yang YC, Fan XN, Shi JG, Hu JF. 2008.
Glycosides from the root of Iodes cirrhosa. J Nat Prod. 71(4):647–654.
Gawro nꢀ ski JK. 1982. Circular dichroism and stereochemistry of chiral conjugated cyclohexenones.
Tetrahedron. 38(1):3–26.
Hoang LS, Tran MH, Lee JS, Ngo QMT, Woo MH, Min BS. 2016. Inflammatory inhibitory activity
of sesquiterpenoids from Atractylodes macrocephala rhizomes. Chem Pharm Bull. 64(5):
507–511.
Kamauchi H, Kinoshita K, Takatori K, Sugita T, Takahashi K, Koyama K. 2015. New sesquiterpe-
noids isolated from Atractylodes lancea fermented by marine fungus. Tetrahedron. 71(13):
1909–1914.
Kitajima J, Kamoshita A, Ishikawa T, Takano A, Fukuda T, Isoda S, Ida Y. 2003. Glycosides of
Atractylodes lancea. Chem Pharm Bull. 51(6):673–678.
Li YZ, Dai M, Peng DY. 2017. New bisesquiterpenoid lactone from the wild rhizome of
Atractylodes macrocephala Koidz grown in Qimen. Nat Prod Res. 31(20):2381–2386.
Nakai Y, Kido T, Hashimoto K, Kase Y, Sakakibara I, Higuchi M, Sasaki H. 2003. Effect of the rhi-
zomes of Atractylodes lancea and its constituents on the delay of gastric emptying. J
Ethnopharmacol. 84(1):51–55.
Resch M, Steigel A, Chen ZL, Bauer R. 1998. 5-Lipoxygenase and Cyclooxygenase-1 Inhibitory
Active Compounds from Atractylodes lancea. J Nat Prod. 61(3):347–350.
Sakurai T, Sugawara H, Saito K, Kano Y. 1994. Effects of the acetylene compound from
Atractylodes rhizome on experimental gastric ulcers induced by active oxygen species. Biol
Pharm Bull. 17(10):1364–1368.
Wang CZ, Yu DQ. 1998. Lignan and acetylenic glycosides from Aster auriculatus. Phytochemistry.
48(4):711–717.
Wang HX, Liu CM, Liu Q, Gao K. 2008. Three types of sesquiterpenes from rhizomes of
Atractylodes lancea. Phytochemistry. 69(10):2088–2094.
Xu K, Feng ZM, Yang YN, Jiang JS, Zhang PC. 2016. Eight new eudesmane- and eremophilane-
type sesquiterpenoids from Atractylodes lancea. Fitoterapia. 114:115–121.
Xu K, Jiang JS, Feng ZM, Yang YN, Li L, Zang CX, Zhang PC. 2016. Bioactive sesquiterpenoid and
polyacetylene glycosides from Atractylodes lancea. J Nat Prod. 79(6):1567–1575.
Xu K, Yang YN, Feng ZM, Jiang JS, Zhang PC. 2016. Six new compounds from Atractylodes lancea
and their hepatoprotective activities. Bioorg Med Chem Lett. 26(21):5187–5192.
Xu WH, Zhao P, Wang M, Liang Q. 2018. Naturally occurring furofuran lignans: structural diver-
sity and biological activities. Nat Prod Res. doi:10.1080/14786419.2018.1474467.
Yahara S, Higashi T, Iwaki K, Nohara T, Marubayashi N, Ueda I, Kohda H, Goto K, Izumi H, Nuno
M, et al. 1989. Studies on the constituents of Atractylodes lancea. Chem Pharm Bull. 37(11):
2995–3000.
Yang YN, Liu ZZ, Feng ZM, Jiang JS, Zhang PC. 2012. Lignans from the root of Rhodiola crenu-
lata. J Agric Food Chem. 60(4):964–972.
Yin M, Xiao CC, Chen Y, Wang M, Guan FQ, Wang QZ, Shan Y, Feng X. 2015. A new sesquiterpe-
noid glycoside from rhizomes of Atractylodes lancea. Chin Tradit Herbal Drugs. 7(4):371–374.