A new diarylheptanoid and a new diarylheptanoid glycoside isolated from the roots of Juglans mandshurica and their anti-inflammatory activities

Article abstract of DOI:10.1080/14786419.2017.1408100

A new diarylheptanoid, (2S,3S,5S)-2,3,5-trihydroxy-1,7-bis(4-hydroxy- 3-methoxyphenyl)heptane (1), and a new diarylheptanoid glycoside, (2S,3S,5S)-2,3-dihydroxy-5-O-β-d-xylopyranosyl-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)heptane (2), together with three known compounds, rhoiptelol C (3), rhoiptelol B (4) and 3′,4″-epoxy-2-O-β-d-glucopyanosyl-1-(4-hydroxyphenyl)- 7-(3-methoxyphenyl)heptan-3-one (5) were isolated from the roots of Juglans mandshurica (Juglandaceae). The structures of compounds 1 and 2 were identified based on HR-ESI-MS, 1D and 2D NMR spectroscopic methods. Compounds 1–5 were assayed for their inhibitory effects on the production of NO, TNF-α and IL-6 in LPS-stimulated RAW264.7 cells.

Full text of DOI:10.1080/14786419.2017.1408100

Natural Product Research
Formerly Natural Product Letters
ISSN: 1478-6419 (Print) 1478-6427 (Online) Journal homepage: http://www.tandfonline.com/loi/gnpl20
A new diarylheptanoid and a new diarylheptanoid
glycoside isolated from the roots of Juglans
mandshurica and their anti-inflammatory
activities
Shengbao Diao, Mei Jin, Jinfeng Sun, Yi Zhou, Chao Ye, Yong Jin, Wei Zhou &
Gao Li
To cite this article: Shengbao Diao, Mei Jin, Jinfeng Sun, Yi Zhou, Chao Ye, Yong Jin, Wei Zhou
& Gao Li (2017): A new diarylheptanoid and a new diarylheptanoid glycoside isolated from the
roots of Juglans mandshurica and their anti-inflammatory activities, Natural Product Research, DOI:
10.1080/14786419.2017.1408100
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Date: 06 December 2017, At: 04:33

Natural Product research, 2017
https://doi.org/10.1080/14786419.2017.1408100
A new diarylheptanoid and a new diarylheptanoid glycoside
isolated from the roots of Juglans mandshurica and their anti-
inflammatory activities
Shengbao Diaoa†, Mei Jina,b†, Jinfeng Suna, Yi Zhoua, Chao Yea, Yong Jina, Wei Zhoua
and Gao Lia
aKey laboratory of Natural resources of changbai Mountain and Functional Molecules, Ministry of education,
b
Yanbian university college of Pharmacy, Yanji, P.r. china; department of Pharmacy, Postdoctoral research
station, Yanbian university hospital, Yanji, P.r. china
ABSTRACT
ARTICLE HISTORY
received 13 september 2017
accepted 9 November 2017
A new diarylheptanoid, (2S,3S,5S)-2,3,5-trihydroxy-1,7-bis(4-hydroxy-
3-methoxyphenyl)heptane (1), and a new diarylheptanoid glycoside,
(2S,3S,5S)-2,3-dihydroxy-5-O-β-d-xylopyranosyl-7-(4-hydroxy-3-
methoxyphenyl)-1-(4-hydroxyphenyl)heptane (2), together with three
known compounds, rhoiptelol C (3), rhoiptelol B (4) and 3′,4″-epoxy-
2-O-β-d-glucopyanosyl-1-(4-hydroxyphenyl)- 7-(3-methoxyphenyl)
heptan-3-one (5) were isolated from the roots of Juglans mandshurica
(Juglandaceae). The structures of compounds 1 and 2 were identified
based on HR-ESI-MS, 1D and 2D NMR spectroscopic methods.
Compounds 1–5 were assayed for their inhibitory effects on the
production of NO, TNF-α and IL-6 in LPS-stimulated RAW264.7 cells.
KEYWORDS
Juglans mandshurica;
Juglandaceae;
diarylheptanoids; No
production; tNF-α
production; Il-6 production
1. Introduction
Juglans mandshurica Maxim. is a well-known member of the Juglandaceae family. The roots,
leaves, fruits and stem bark have been used as traditional folk medicines to treat cancer,
CONTACT Wei Zhou
zhouwei8452@163.com; Gao li
gli@ybu.edu.cn
†these authors contributed equally to the work.
supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2017.1408100.
© 2017 Informa uK limited, trading as taylor & Francis Group

2
S. DIAO ET AL.
leucorrhoea, diarrhoea and gastritis in northeast China and Korea (Park et al. 2012, 2017).
To date, several diarylheptanoids, quinones, naphthalenes, tetralones and phenolic com-
pounds (Kim et al. 1998; Lee et al. 2002; Li et al. 2003a, 2003b, 2004, 2005, 2007, 2009; Machida
et al. 2008; Yao et al. 2012; Lin et al. 2013; Jin et al. 2015; Yao et al. 2015; Jin et al. 2016; Zhou
et al. 2017) have been reported from J. mandshurica. These constituents showed various
bioactivities, such as antitumour (Kim et al. 1998; Li et al. 2003a, 2003b, 2007, 2009; Yao
et al. 2012), antioxidant (Ngoc et al. 2008), anti-inflammatory (Ju et al. 2009) and anti-com-
plement activities (Min et al. 2003). As a continuation of our phytochemical investigations,
a new diarylheptanoid (1) and a new diarylheptanoid glycoside (2), along with three known
diarylheptanoids (3–5) were isolated from the roots of J. mandshurica. This paper describes
the isolation and structural elucidation of new compounds 1 and 2 based on HR-ESI-MS, 1D
and 2D NMR spectroscopic methods. Compounds 1–5 were assayed for their inhibitory
effects on the production of NO, TNF-α and IL-6 in LPS-stimulated RAW264.7 cells.
2. Results and discussion
2.1. New compound structure elucidation
A new diarylheptanoid (1) and a new diarylheptanoid glycoside (2) and three known dia-
rylheptanoids (3–5) were isolated from an EtOAc extract of J. mandshurica roots. The three
known compounds were identified as rhoiptelol C (3) (Jiang et al. 1996), rhoiptelol B (4)
(Reddy et al. 2010) and 3′,4″-epoxy-2-O-β- -glucopyanosyl-1-(4-hydroxyphenyl)-7-(3-meth-
d
oxyphenyl) heptan-3-one (5) (Kim et al. 1998) by comparing their NMR spectroscopic data
with published values (Figure 1).
Compound 1 was obtained as a light yellow powder. Its molecular formula was assigned
as C21H28O7 based on the [M + H]+ peak at m/z 393.1923 (calcd. 393.1908) in the HR-ESI-MS
1
spectrum. The H NMR spectrum of 1 showed signals for two sets of 1,3,4-trisubstituted
aromatic rings at δH 6.87 (1H, d, J = 1.5 Hz, H-2′), 6.79 (1H, d, J = 1.7 Hz, H-2″), 6.74 (1H, d,
J = 8.0 Hz, H-5′), 6.72 (1H, d, J = 8.0 Hz, H-5″), 6.71 (1H, dd, J = 1.5, 8.0 Hz, H-6′), and 6.64 (1H,
dd, J = 1.7, 8.0 Hz, H-6″), with two methoxyl protons at δH 3.86 (3H, s, 3′-OCH3) and 3.85 (3H,
s, 3″-OCH3). The 13C-NMR spectrum exhibited a total of 21 carbon signals, including two
benzene rings with twelve carbons at δC 148.8 (C-3′), 148.7 (C-3″), 145.8 (C-4′), 145.4 (C-4″),
135.2 (C-1″), 132.1 (C-1′), 122.9 (C-6′), 121.8 (C-6″), 116.1 (C-5″), 116.0 (C-5′), 114.2 (C-2′), and
113.1 (C-2″), three oxygenated methines at δC 76.4 (C-2), 72.9 (C-3), and 70.7 (C-5), two meth-
oxyl groups at δC 56.3 (3′-OCH3, 3″-OCH3) and four methylene groups at δC 40.9 (C-6), 40.8
(C-4), 40.1 (C-1), and 32.3 (C-7). The 1H–1H COSY spectrum showed connectivities from H-1
to H-7 on the aliphatic chain. In the HMBC spectrum of 1, the connectivities of the two aro-
matic rings with the aliphatic chain were indicated by cross peaks between H-1 and C-2′ and
C-6′, and between H-7 and C-2″ and C-6″. The positions of the two methoxyl groups on the
two aromatic rings of 1 were determined by both the HMBC correlation of C-3′ with 3′-OCH3
and of C-3″ with 3″-OCH3, and NOE cross peaks between H-2′ and 3′-OCH3 and between C-2″
and 3″-OCH3 in the NOESY spectrum (Figure S1). Taken together, the structure of compound
1 was similar to that of 2,3,5-trihydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)heptane (Li
25
et al. 2005), except for its specific rotation data. The optical rotation value ([α] = −24.2,
D
20
MeOH) of compound 1 was different from that in the literature ([α] + 15.91, MeOH) (Li et
D
al. 2005). The relative configuration of compound 1 was determined by NOESY correlations,

NATURAL PRODUCT RESEARCH
3
which showed interaction of H-2 with H-3 and of H-3 with H-5, suggesting that these hydro-
gen atoms were in erythro configurations (Wu et al. 2012; Wei et al. 2016; Zhang et al. 2017).
15
Additionally, comparison of its optical rotation with that of rhoiptelol C ([α] = −24.0, MeOH)
D
(Jiang et al. 1996) indicated the configuration of 1 was 2S, 3S, 5S. Therefore, compound 1
was identified as (2S,3S,5S)-2,3,5-trihydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl) heptane.
Compound 2 was obtained as a light yellow powder. Its molecular formula was deter-
mined to be C25H34O10 based on the [M + H]+ peak at m/z 495.2240 (calcd. 495.2225) in the
HR-ESI-MS spectrum. The 1H-NMR spectrum of 2 showed proton signals for 1,4-disubstituted
and 1,3,4-trisubstituted aromatic rings and a methoxyl proton. The 13C-NMR and DEPT spectra
displayed a total of 25 carbon signals comprising three hydroxymethine, four methylene,
one methoxy and twelve aromatic carbons and five carbons associated with a sugar unit,
suggesting a diarylheptanoid glycoside with an 1,7-diphenylheptane structural skeleton
and a pentose moiety. Acid hydrolysis of 2 gave rhoiptelol C (3) and d-xylose. The configu-
ration of the anomeric proton of the xylopyranosyl group was proposed to be β from the
coupling constant (7.7 Hz) of the proton peak at δ 4.29. A long-range correlation was
observed from the anomeric proton H-1‴ of the β-d-xylose to C-5 of the heptane moiety in
the HMBC spectrum (Figure S1). The relative configuration of compound 2 was determined
by NOESY correlations, which showed interaction of H-2 with H-3 and of H-3 with H-5, sug-
gesting that these hydrogen atoms were in the same plane (Wu et al. 2012; Wei et al. 2016;
Zhang et al. 2017). Additionally, the aglycone of compound 2 was identical to rhoiptelol C
(3). Thus, the structure of compound 2 was elucidated as (2S,3S,5S)-2,3-dihydroxy-5-O-β-d-
xylopyranosyl-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)heptane.
2.2. Inhibitory activities against NO, TNF-α and IL-6 production
Compounds 1–5 were assayed for their inhibitory effects on the production of NO, TNF-α
and IL-6 in LPS-stimulated RAW264.7 cells. First, cell viability was determined by MTT assay,
the results showed that compounds 1–5 had no significant cytotoxicity in RAW 264.7 cells
at 100 μM (Figure S2). Compounds 1–5 on the production of NO, TNF-α and IL-6 in LPS-
induced RAW 264.7 cells were tested using the Griess and Elissa method. The results demon-
strated that compounds 4 and 5 could significantly inhibit NO, TNF-α and IL-6 production
at 3, 10, 30 and 100 μM in a dose-dependent manner. Compounds 1 and 3 showed significant
NO, TNF-α and IL-6 production inhibitory effects at 10, 30, and 100 μM. Compound 2 signif-
cantly inhibited NO and TNF-α production at 3, 10, 30 and 100 μM in a dose-dependent
manner, IL-6 production inhibitory effects at 10, 30, and 100 μM (Figures S3–5).
3. Experimental
3.1. General experimental procedures
The NMR spectra were recorded on a Bruker AV 600, 500 and 300 MHz spectrometer
(Fällanden, Switzerland). HR-ESI-MS spectra were recorded on a Bruker microTOF QII mass
spectrometer (Bruker Daltonics, Fremont, CA, USA). Preparative HPLC was carried out on a
Bonna-Agela FL-LC050 series chromatograph (Bonna-Agela Technologies Co., Ltd., Tianjin,
China). Middle pressure liquid chromatography (MPLC) was performed on an automatic
flash chromatography device (CHEETAH MP-200, Bonna-Agela Technologies Co., Ltd.).

4
S. DIAO ET AL.
Column chromatography was performed using silica gel (200–300 mesh, Qingdao Haiyang
Chemical Co., Ltd., Qingdao, China). TLC was performed with precoated silica gel GF254 glass
plates (200 × 200 mm, Qingdao Haiyang Chemical Co., Ltd.). All other chemicals and solvents
were of analytical grade and without further purification (Figure 1).
3.2. Plant material
J. mandshurica roots were collected in a mountainous area ofYanji, Jilin, China in Aug., 2013,
and identified taxonomically by Prof. Huizi Lv, of the College of Pharmacy, Yanbian University.
A voucher specimen (voucher number: YB-SYC-1302) was deposited at the College of
Pharmacy, Yanbian University.
3.3. Extraction and isolation
Air-dried and powdered roots of J. mandshurica (10 kg) were extracted with 75% EtOH (3 × 50
L) at room temperature. The combined extracts were concentrated under a vacuum to obtain
a crude extract (1124.2 g). The crude extract was suspended in H2O (2 L) and partitioned
sequentially with CH2Cl2, EtOAc and n-BuOH (3 × 2 L in each case). The EtOAc extract (307.3 g)
was purified by column chromatography using silica gel and eluted with a CH2Cl2–MeOH
gradient (from 100% CH2Cl2 to 100% MeOH, v/v) to obtain 11 fractions (Fr. 1–11). Fr. 6 (3.3 g)
was chromatographed by MPLC using a Bonna-Agela FCH120-S cartridge and eluted with
a CH2Cl2–MeOH gradient (from 100% CH2Cl2 to 100% MeOH, v/v, 2000 mL, flow rate: 10 mL/
min) to afford six subfractions (Fr.6-1–6-6). Fr. 6–2 (88.6 mg) was purified by MPLC (Bonna-
Agela Flash column, CO140040-0, 40–60 μm, ODS, 12 g) with MeOH–H2O (from 5:5 to 9:1,
v/v, 1500 mL, flow rate: 12 mL/min), followed by preparative HPLC with MeOH–H2O gradients
(7:3, v/v, 200 mL, flow rate: 0.5 mL/min) to afford 3 (7.3 mg, tR 65 min) and 4 (6.5 mg, tR
102 min). Fr. 6-3 (108.6 mg) was purified by column chromatography using silica gel and
eluted with a CH2Cl2–MeOH gradient (from 15:1 to 5:1, v/v) to afford 5 (4.2 mg). Fr. 6-4
(15.8 mg) was applied to HPLC (MeOH–H2O, 1:2, v/v, 200 mL, flow rate: 0.8 mL/min) to yield
Figure 1. structures of compounds1–5 from Juglans mandshurica.

NATURAL PRODUCT RESEARCH
5
1 (6.1 mg, tR 105 min). Fr. 9 (2.2 g) was separated chromatographically using silica gel eluted
with a CH2Cl2–MeOH gradient (from 30:1 to 10:1, v/v) to afford five subfractions (Fr.9-1–9-5).
Fr.9-3 (86.4 mg) was purified by MPLC (SO230012-0, C18, 12 g) with MeOH–H2O (3:7, v/v),
followed by preparative HPLC with MeCN–H2O gradients (3:7, v/v, 200 mL, flow rate: 1 mL/
min) to afford 2 (7.3 mg, tR 36 min).
(2S,3S,5S)-2,3,5-trihydroxy-1,7-bis(4-hydroxy- 3-methoxyphenyl)heptane (1): light yellow-
25
ish powder, HR-ESI-MS m/z 393.1923 [M + H]+ (calcd. for C H O , 393.1908). [α] = -24.2
D
21 28
7
(c 0.19, MeOH); 1H-NMR (CD3OD, 600 MHz) δ 6.87 (1H, d, J = 1.5 Hz, H-2′), 6.79 (1H, d, J = 1.7 Hz,
H-2′′), 6.74 (1H, d, J = 8.0 Hz, H-5′), 6.72 (1H, d, J = 8.0 Hz, H-5′′), 6.71 (1H, dd, J = 1.5, 8.0 Hz,
H-6′), 6.64 (1H, dd, J = 1.7, 8.0 Hz, H-6′′), 3.86 (3H, s, 3′-OCH3), 3.85 (3H, s, 3′′-OCH3), 3.82 (1H,
m, H-5), 3.71 (1H, ddd, 3.2, 4.7, 8.0 Hz, H-3), 3.66 (1H, ddd, J = 3.2, 5.0, 8.0 Hz, H-2), 2.85 (1H,
dd, J = 5.2, 13.8 Hz, H-1a), 2.85 (2H, m, H-7a,1b), 2.59 (1H, ddd, J = 6.5, 9.7, 13.7 Hz, H-7b), 1.74
(4H, m, H-4, 6); 13C-NMR (CD3OD, 150 MHz) 148.8 (C-3′), 148.7 (C-3′′), 145.8 (C-4′), 145.4 (C-4′′),
135.2 (C-1′′), 132.1 (C-1′), 122.9 (C-6′), 121.8 (C-6′′), 116.1 (C-5′′), 116.0 (C-5′), 114.2 (C-2′), 113.1
(C-2′′), 76.4 (C-2), 72.9 (C-3), 70.7 (C-5), 56.3 (3′-OCH3/3′′-OCH3), 40.9 (C-6), 40.8 (C-4), 40.1
(C-1), 32.3 (C-7).
(2S,3S,5S)-2,3-dihydroxy-5-O-β-D-xylopyranosyl-7-(4-hydroxy-3-methoxyphenyl)-1-(4-
25
hydroxyphenyl)heptane (2): light yellowish powder; [α] = -26.0 (c 0.08, MeOH); HR-ESI-MS:
D
m/z = 495.2240 [M + H]+ (calcd. for C25H34O10, 495.2225); 1H NMR (CD3OD, 500 MHz) δ 7.10
(2H, d, J = 8.5 Hz, H-2′, 6′), 6.78 (1H, d, J = 1.8 Hz, H-2′′), 6.73 (2H, J = 8.5 Hz, H-3′, 5′), 6.71 (1H,
d, J = 8.0 Hz, H-5′′), 6.61 (1H, dd, J = 8.0, 1.8 Hz, H-6′′), 4.29 (1H, d, J = 7.7 Hz, H-1′′′), 3.87 (1H,
m, H-5′′′a), 3.85 (3H, s, 3″-OCH3), 3.86 (1H, m, H-5), 3.66 (1H, m, H-2), 3.61 (1H, m, H-3), 3.53
(1H, m, H-4′′′), 3.33 (1H, m, H-3′′′), 3.21 (2H, m, H-2′′′, H-5′′′b), 2.83 (1H, dd, J = 5.4, 13.7 Hz,
H-1a), 2.65 (1H, dd, J = 7.8, 13.6 Hz, H-1b), 2.63 (2H, m, H-7),1.84 (4H, m, H-4, 6); 13C NMR
(CD3OD, 125 MHz) δ 156.7 (C-4′), 149.0 (C-3′′), 145.4 (C-4′′), 135.5 (C-1′), 131.41 (C-2′,6′), 131.37
(C-1′′), 121.9 (C-6′′), 116.1 (C-3′, 5′, 5′′), 111.3 (C-2′′), 104.4 (C-1′′′), 79.4 (C-5), 78.1 (C-3′′′), 76.7
(C-2), 75.1 (C-2′′′), 71.6 (C-3), 71.3 (C-4′′′), 67.0 (C-5′′′), 56.4 (3′′-OCH3), 39.5 (C-1), 38.7 (C-4),
38.4 (C-6), 31.9 (C-7).
3.4. Acid hydrolysis of 2 and sugar determination
Compound 2 was hydrolysed with 1.0 m HCl at 85 °C for 2 h and the reaction mixture was
partitioned with EtOAc. The EtOAc residue was dissolved in dry pyridine after the addition
of L-cysteine methyl ester hydrochloride and heated at 60 °C for 2 h. The trimethylsilylimi-
dazole was added followed by heating at 60 °C for 2 h, and the mixture was evaporated. The
dried product was partitioned with n-hexane and H2O. The n-hexane layer was analysed by
GC and the retention times of monosaccharide moiety were as follows: -xylose (tR 8.21) and
d
l-xylose (tR 8.66). The hydrolysate of compound 2 was detected at tR 8.21 min for d-xylose.
3.5. Cytokine production assay
RAW 264.7 cells were incubated in 48-well plates containing 1 × 105 cells per well, and then
treated with compounds at 3, 10, 30, and 100 μM concentration for 2 h before stimulation
with LPS (1μg/mL). Supernatants were harvested after 24 h stimulation. Production of NO
was measured using the Griess assay followed the manufacture instruction. And the

6
S. DIAO ET AL.
concentrations ofTNF-α and IL-6 in the culture supernatants were determined by ELISA assay
according to the instructions of manufacture. The data are presented as means standard
deviation (SD) of three independent experiments.
4. Conclusion
This paper deals with the isolation and structural elucidation of a new diarylheptanoid (1),
and a new diarylheptanoid glycoside (2), together with three known diarylheptanoids (3–5)
from the roots of J. mandshurica. This study showed that new chemical compositions remain
undiscovered in this plant and will be worth for further research deeply. Moreover, this study
exhibited that diarylheptanoid and their derivatives from J. mandshurica inhibit the produc-
tion of pro-inflammatory cytokines NO, TNF-α and IL-6 in LPS-stimulated RAW 264.7 cells.
The bioactive results presented herein demonstrated that the various diarylheptanoids in
J. mandshurica could contribute to their observed anti-inflammatory effect.
Acknowledgments
We thank Robbie Lewis, MSc, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing
the English text of a draft of this manuscript.
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
81660699, 81660579 and 81760627]. And also supported in part by the Jilin Provincial Education
Department [grant number 2016-280].
References
Jiang Z, TanakaT, Hirata H, Fukuoka R, Kouno, I. 1996. Three diarylheptanoids from Rhoiptelea chiliantha.
Phytochemistry. 43(5):1049–1054.
Jin M, Diao S, Zhang C, Cao S, Sun J, Li R, Jiang Z, Zheng M, Son JK, Li G. 2015. Two new diarylheptanoids
isolated from the roots of Juglans mandshurica. Nat Prod Res. 29(19):1839–1844.
Jin M, Sun J, Li R, Diao S, Zhang C, Cui J, Son JK, Zhou W, Li G. 2016. Two new quinones from the roots
of Juglans mandshurica. Arch Pharm Res. 39(9):1237–1241.
Ju SM, Song HY, Lee SJ, Seo WY, Sin DH, Goh AR, KangYH, Kang IJ, Won MH, Yi JS, et al. 2009. Suppression
of thymus- and activation-regulated chemokine (TARC/CCL17) production by 1,2,3,4,6-penta-O-
galloyl-β-d-glucose via blockade of NF-κB and STAT1 activation in the HaCaT cells. Biochem Bioph
Res Co. 387(1):115–120.
Kim SH, Lee KS, Son JK, Je GH, Lee JS, Lee CH, Cheong CJ. 1998. Cytotoxic compounds from the roots
of Juglans mandshurica. J Nat Prod. 61(5):643–645.
Lee KS, Li G, Kim SH, Lee CS, Woo MH, Lee SH, Jhang YD, Son JK. 2002. Cytotoxic diarylheptanoids from
the roots of Juglans mandshurica. J Nat Prod. 65(11):1707–1708.
Li G, Lee SY, Lee KS, Lee SW, Kim SH, Lee SH, Lee CS, Woo MH, Son JK. 2003a. DNA topoisomerases I and II
inhibitory activity of constituents isolated from Juglans mandshurica. Arch Pharm Res. 26(6):466–470.
Li G, Xu ML, Choi HG, Lee SH, Jahng YD, Lee CS, Moon DC, Woo MH, Son JK. 2003b. Four new
diarylheptanoids from the roots of Juglans mandshurica. Chem Pharm Bull. 51(3):262–264.

NATURAL PRODUCT RESEARCH
7
Li G, Seo CS, Lee SH, Jahng YD, Chang HW, Lee CS, Woo MH, Son JK. 2004. Diarylheptanoids from the
roots of Juglans mandshurica. B Korean Chem Soc. 25:397–399.
Li G, Cui JM, Kwon YJ, Seo CS, Lee CS, Woo MH, Lee ES, Jahng YD, Chang HW, Lee SH, Son JK. 2005. Two
new diarylheptanoids from Juglans mandshurica. B Korean Chem Soc. 26:1878–1880.
Li ZB, Wang JY, Jiang B, Zhang XL, An LJ, Bao YM. 2007. Benzobijuglone, a novel cytotoxic compound
from Juglans mandshurica, induced apoptosis in HeLa cervical cancer cells. Phytomedicine.
14(12):846–852.
Li ZB, Wang JY, Yang J, Zhang XL, An LJ, Bao YM. 2009. Apoptosis of BGC823 cell line induced by
p-hydroxymethoxybenzobijuglone, a novel compound from Juglans mandshurica. Phytother Res.
23(4):551–557.
Lin H, Zhang YW, Bao YL, Wu Y, Sun LG, Yu CL, Huang YX, Wang EB, Li YX. 2013. Secondary metabolites
from the stem bark of Juglans mandshurica. Biochem Syst Ecol. 51:184–188.
Machida K, Suzuki A, YogiashiY, Kikuchi M. 2008. Studies on the constituents of Juglans Species. II New
Diarylheptanoids from the Bark of Juglans mandshurica Maxim. var. sieboldiana Makino. J Tohoku
Pharm Univ. 55:41–46.
Min BS, Lee SY, Kim JH, Lee JK, Kim TJ, Kim DH, Kim YH, Joung H, Lee HK, Nakamura N, et al. 2003. Anti-
complement activity of constituents from the stem-bark of Juglans mandshurica. Biol Pharm Bull.
26(7):1042–1044.
Ngoc TM, Hung TM, Thuong PT, Kim JC, Choi JS, Bae KH, Hattori M, Choi CS, Lee JS, Min BS. 2008.
Antioxidative activities of galloyl glucopyranosides from the stem-bark of Juglans mandshurica.
Biosci Biotechnol Biochem. 72(8):2158–2163.
Park GH, Jang DS, Oh MS. 2012. Juglans mandshurica leaf extract protects skin fibroblasts from damage
by regulating the oxidative defense system. Biochem Biophys Res Commun. 421(2):343–348.
Park S, Kim N, Yoo G, Kim SN, Kwon HJ, Jung K, Oh DC, Lee YH, Kim SH. 2017. Phenolics and neolignans
isolated from the fruits of Juglans mandshurica Maxim. and their effects on lipolysis in adipocytes.
Phytochemistry. 137:87–93.
Reddy CR, Rao NN, Srikanth B. 2010. Total synthesis of a diarylheptanoid, rhoiptelol B. Eur J Org Chem.
2010(2):345–351.
Wei N, Zhou Z, Wei Q, Wang Y, Jiang J, Zhang J, Wu L, Dai S, Li Y. 2016. A novel diarylheptanoid-bearing
sesquiterpene moiety from the rhizomes of Alpinia officinarum. Nat Prod Res. 30(20):2344–2349.
Wu H, Cheng M, Peng C, Yang S, Chang H, Lin C, Wang C, Chen I. 2012. Secondary metabolites from the
stems of Engelhardia roxburghiana and their antitubercular activities. Phytochemistry. 82:118–127.
YaoY, ZhangYW, SunLG, LiuB, BaoYL, LinH, ZhangY, ZhengLH, SunY,YuCL, etal. 2012. Juglanthraquinone
C, a novel natural compound derived from Juglans mandshurica Maxim, induces S phase arrest and
apoptosis in HepG2 cells. Apoptosis. 17(8):832–841.
Yao DL, Zhang C, Luo J, Jin M, Zheng MS, Cui JM, Son JK, Li G. 2015. Chemical constituents from the
leaves of Juglans mandshurica. Arch Pharm Res. 38(4):480–484.
ZhangY, Ruan J, Li J, Chao L, Shi W, Yu H, Gao X, Wang T. 2017. Bioactive diarylheptanoids and stilbenes
from the rhizomes of Dioscorea septemloba Thunb. Fitoterapia. 117:28–33.
ZhouYY, Liu QY, Yang BY, JiangYQ, LiuYX, WangY, Guo S, Kuang H. 2017. Two new cytotoxic glycosides
isolated from the green walnus husks of Juglans mandshurica Maxim. Nat Prod Res. 31(11):1237–1244.