A new phenolic glycoside from the Idesia polycarpa Maxim. leaves

Article abstract of DOI:10.1080/14786419.2018.1511553

Phytochemical investigation on the ethyl acetate extract of Idesia polycarpa Maxim. Leaves led to the isolation of four phenolic glycoside isomers (1–4). Compound 2 appeared to be new reported phenolic glycoside, while compound 1 was the first time isolated from the titled species. Their structures were established by IR, UV, HRESI-MS and 1D and 2D NMR spectroscopies analysis and comparison of spectral data with previously reported data. The compounds 3 and 4 showed stronger activity of scavenging the DPPH free radical than the other two compounds, while the compounds 1 and 2 showed a significant activity of scavenging the ABTS free radical. Compounds 2 and 4 exhibited stronger cytotoxicity against HepG2 cell lines compared to compounds 1 and 3. Moreover, compound 3 presented the highest cytotoxicity against MCF cell lines with IC₅₀ value of 37.17 ± 0.26 μg/mL than compounds 1, 2 and 4.

Full text of DOI:10.1080/14786419.2018.1511553

Natural Product Research
Formerly Natural Product Letters
ISSN: 1478-6419 (Print) 1478-6427 (Online) Journal homepage: http://www.tandfonline.com/loi/gnpl20
A new phenolic glycoside from the Idesia polycarpa
Maxim. leaves
Lei Huang, Tong Peng, Yu Li, Yunyun He, Li Wang, Shiyan Zhang, Yiran Sun,
Fang Chen & Lin Tang
To cite this article: Lei Huang, Tong Peng, Yu Li, Yunyun He, Li Wang, Shiyan Zhang, Yiran Sun,
Fang Chen & Lin Tang (2018): A new phenolic glycoside from the Idesiaꢀpolycarpa Maxim. leaves,
Natural Product Research, DOI: 10.1080/14786419.2018.1511553
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NATURAL PRODUCT RESEARCH
https://doi.org/10.1080/14786419.2018.1511553
SHORT COMMUNICATION
A new phenolic glycoside from the Idesia polycarpa
Maxim. leaves
a,b
b,c
a,b
b,c
b,c
b,c
Lei Huang , Tong Peng , Yu Li , Yunyun He , Li Wang , Shiyan Zhang ,
b,c
a,b,c
a,b,c
Yiran Sun , Fang Chen
and Lin Tang
a
Institute of New Energy and Low-Carbon Technology, Sichuan University, Chengdu, P.R. China ;
b
National and Local Joint Engineering Laboratory for Energy Plant Bio-Oil Production and
c
Application, Chengdu, P.R. China; Key Laboratory of Bio-resources and Eco-environment of Ministry
of Education, College of Life Sciences, Sichuan University, Chengdu, P.R. China
ABSTRACT
ARTICLE HISTORY
Phytochemical investigation on the ethyl acetate extract of Idesia
polycarpa Maxim. Leaves led to the isolation of four phenolic
glycoside isomers (1–4). Compound 2 appeared to be new
reported phenolic glycoside, while compound 1 was the first time
isolated from the titled species. Their structures were established
by IR, UV, HRESI-MS and 1D and 2D NMR spectroscopies analysis
and comparison of spectral data with previously reported data.
The compounds 3 and 4 showed stronger activity of scavenging
the DPPH free radical than the other two compounds, while the
compounds 1 and 2 showed a significant activity of scavenging
the ABTS free radical. Compounds 2 and 4 exhibited stronger
cytotoxicity against HepG2 cell lines compared to compounds 1
and 3. Moreover, compound 3 presented the highest cytotoxicity
against MCF cell lines with IC50 value of 37.17 ± 0.26 lg/mL than
compounds 1, 2 and 4.
Received 21 April 2018
Accepted 10 August 2018
KEYWORDS
Idesia polycarpa Maxim.;
phenolic glycoside isomers;
cytotoxicity; antioxidant
1. Introduction
Idesia polycarpa Maxim., a kind of deciduous tree in the Salicaceae family (Chou et al.
997; Feistel et al. 2017), originates from Asia including China, Korea and Japan (Jung
1
et al. 2010), and forms edible orange berry-like fruits that can remain on the tree after
leaf senescence (Feistel et al. 2017). The oil from fruit of the plant is becoming a
CONTACT Lin Tang
tanglin@scu.edu.cn
Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2018.1511553.
ß 2018 Informa UK Limited, trading as Taylor & Francis Group

2
L. HUANG ET AL.
Figure 1. Chemical structures of phenolic glycosides isomers (1–4).
popular cooking oil for many years in China due to its healthcare values and thera-
peutic effects on human body (Yang et al. 2014). The seeds of this tree were reported
to utilised as an insecticide in Korea, and the leaves showed hemostatic activity (Kim
et al. 2005). So far, many phenolic glycosides such as idescarpin, idesin, idesolide and
salirepin have been isolated from the plant (Chou et al. 1997; Kim et al. 2005;
Moritake et al. 1987), which are structurally related to salicinoids that are known as
defense compounds of Populus and Salix species (Feistel et al. 2017). Previous studies
have found that idescarpin has the skin-whiting effect (Baek et al. 2006). Idesin and
salirepin extracted from defatted fruit residue also have anti-inflammatory activities
(Kim et al. 2007) and idesolide can significantly reduce nitric oxide production induced
by lipopolysaccharide in BV2 microglial cells (Kim et al. 2005).
Our previous study investigated the activities of the phenolics from the fruit and
found it had depigmenting and antioxidant activities (Ye et al. 2014). During the
course of our research on bioactive compounds from I. polycarpa Maxim., the EtOAc-
soluble fraction of the leaves was subjected to a phytochemical investigation, resulting
in the isolation and structural characterization of the four phenolic glycoside isomers,
including a new phenolic glycoside: compound 2 and three known compounds (1, 3,
and 4) (Figure 1). Their structures were analyzed and confirmed unambiguously by
1
13
nuclear magnetic resonance spectrometry ( H NMR, C NMR and 2D NMR) in combin-
ation with the comparison of the data for the known related compounds, which had
reported by the previous study (Kim et al. 2005). To date, there have not been
reported any research about the antioxidant and cytotoxicity of the isolated phenolic
glycoside. The antioxidant and cytotoxicity of the four phenolic glycoside isomers
were evaluated by measuring their ability to scavenge the radical of DPPH and ABTS,
and to inhibit the growth of human hepatocytes HepG2 as well as human breast can-
cer MCF cell lines. Our results provide a basis for the development and utilization of
phenolic glycoside isomers.

NATURAL PRODUCT RESEARCH
3
2. Results and discussion
The powdered leaves were extracted with ethanol. The mixed extracts were resus-
pended in water and partitioned with EtOAc. The EtOAc soluble-fraction was success-
fully subject to over HSCCC and prep-HPLC to obtain one new (2) and three known
phenolic glycosides (1, 3 and 4) (Figure 1).
Compound 2, a white powder, had the molecular formula of C H O to be deter-
2
1 22 9
-
mined by HRESI-MS at [M-H] (calcd for C H O , m/z 417.1191) of m/z 417.1159
2
1 21 9
(Figure S3). The UV spectrum showed kmax at 275 and 312 nm, while the IR spectrum
exhibited absorption at 3383 (hydroxyl), 1701 (carbonyl), 1604 and 1513 (aromatic
ꢀ
1
1
13
ring) cm (Figure S8), respectively. The H and C NMR data of compound 2 (Figure
0
0
S4 and S5) showed signals for two sets of AA XX doublets at d 6.82 (2H, d, J ¼ 8.6 Hz,
H
0
0
00
00
00
00
00
H-3 and H-5 ), d 115.0 (C-3 and C5 ) and 7.57 (2H, d, J ¼ 8.6 Hz, H-2 and H-6 ),
C
0
0
00
00
1
(
16.9 (C-3 and C5 ), two cis-olefinic protons at d 6.89 (1H, d, J ¼ 12.8 Hz, H-7 ), 5.79
H
0
0
0
1H, d, J ¼ 12.8 Hz, H-8 ) and a carbonyl function group at d 145.7 (C-1 ), revealing
C
the presence of a p-coumaroyl ester moiety and four aromatic protons at d 7.07 (1H,
H
0
0
0
dd, J ¼ 8.1, 1.3 Hz, H-6 ), 6.81 (1H, overlapped, H-3 ), 6.80 (1H, overlapped, H-4 ) and
0
1
13
6
.62 (1H, m, H-5 ) were assigned for the catechol moiety. Further, the H and C NMR
spectra showed the presence of a hexose unit. The anomeric proton of hexose unit
rasonated at d 4.75 (1H, d, J ¼ 7.4 Hz, H-1). The large coupling constant (J ¼ 7.4 Hz) of
H
the anomeric proton indicated b-configuration of the sugar (Kumar et al. 2010). The
sugar component was identified as D-glucose by acid hydrolysis of compound 2. The
anomeric proton at d 4.75 (1H, d, J ¼ 7.4 Hz, H-1) exhibited the HMBC correlation with
H
0
the carbon resonating at d 147.2 (C-2 ), which confirms the position of the catechol
C
moiety at C-1. The coumaroyl moiety was determined to be attached to the C-6 of the
glucose moiety based on the correlation between the H-6and the carbonyl carbon at
0
d 145.7 (C-1 ) as observed in the HMBC spectrum. Thus, the data of HSQC and HMBC
C
0
confirmed the structure of compound 2 as 1-[(6 -O-(Z)-p-coumaroyl)-b-D-glucopyrano-
syl]-oxy-2-phenol, a new phenolic glycoside (Figure S6 and S7).
Three known phenolic glycosides (Figure 1) were identifiedas 1-[(6 -O-(E)-p-cou-
maroyl)- b-D-glucopyranosyl]-oxy-2-phenol (1) (Kumar et al. 2010), 1-[(4 -O-(E)-p-cou-
0
0
maroyl)-b-D-glucopyranosyl]-oxy-2-phenol (3) (Feistel et al. 2017; Kumar et al. 2010),
0
1
-[(4 -O-(Z)-p-coumaroyl)-b-D-glucopyranosyl]-oxy-2-phenol (4) (Feistel et al. 2017), by
comparison of their NMR and MS data with those previously reported. To the best of
our knowledge, the compound 2 is the first time to be reported as a new kind of
phenolic glycoside, while the compound 1 was isolated from I. polycarpa Maxim for
the first time.
Previous studies have reported that the phenolic exhibited good anticancer and
antioxidant activities (Jessica et al. 2009; John and Shahidi 2010; Vafaei et al. 2018;
Yang et al. 2018). In our study, the four phenolic glycoside isomers showed different
ability of scavenging free radical. Compounds 1 and 2 have significant ability to scav-
enge the ABTS radical compared to that of compounds 3 and 4, and the relative IC50
values were 6.37 ± 0.34 and 6.47 ± 0.13 lg/mL, respectively, while compounds 3 and 4
showed a stronger ability to scavenging the DPPH radical with IC50 values of
21.21 ± 1.74 and 25.56 ± 0.92 lg/mL (Table S2), respectively. Therefore, it indicate that
D-glucose 6-O-linkage to the trans-coumaroyl group (compound 1) and cis-coumaroyl

4
L. HUANG ET AL.
group (compound 2) provided a stronger ability to scavenging the ABTS radical, and
D-glucose 4-O-linkage to the trans-coumaroyl group (compound 3) and cis-coumaroyl
group (compound 4) provided a stronger ability to scavenging the DPPH radical.
Compounds 1–4 were evaluated for its cytotoxicity activity by the MTT assay
towards HepG2 and MCF cell lines. With regard to the function groups of the four
compounds, compounds 2 and 4 have D-glucose 6-O-linkage and 4-O-linkage to the
cis-coumaroyl moiety, and compounds 1 and 3 have D-glucose 6-O-linkage and 4-O-
linkage to the trans-coumaroyl moiety. Furthermore, the D-glucose 6-O-linkage and 4-
O-linkage to the cis-coumaroyl (compounds 2 and 4) possessed better cytotoxic activ-
ity against HepG2 cell lines with IC50 values of 17.89 ± 0.96 and 29.97 ± 0.52 lg/mL,
respectively, than compounds 1 and 3 (42.20 ± 0.95 and 47.87 ± 1.35 lg/mL, respect-
ively). In addition, the 4-O-linkage to the trans-coumaroyl group (compound 3) exhib-
ited higher cytotoxicity against MCF cell lines with IC50 value of 37.17 ± 0.25 lg/mL
compared to compounds 1, 2 and 4 (Table S3). Therefore, we also believe that in this
case the D-glucose 6-O-linkage and 4-O-linkage to the cis-coumaroyl were the active
functional groups that provide better cytotoxic activity against HepG2 cell lines, and
4-O-linkage to the trans-coumaroyl was the active functional group that provide better
cytotoxic activity against MCF cell lines.
3. Conclusions
In this study, a new compound 2, along with three known compounds (1, 3 and 4)
were isolated from the I. polycarpa Maxim. leaves, and compound 1 was isolated from
the plant for the first time. Furthermore, the four phenolic glycoside isomers were first
isolated simultaneously from leaves of the plant. The compounds 1 and 2 can scav-
enge the ABTS free radical better when compared to the compounds 3 and 4 that
were found with stronger activity of scavenging the DPPH free radical. Compounds 2
and 4 possessed more significant cytotoxicity potential against HepG2 cell lines com-
pared to that of compounds 1 and 3, and compound 3 exhibited the highest cytotox-
icity against MCF cell lines than compounds 1, 2 and 4. In addition, further
investigations are still needed to investigate more in vitro and in vivo biological activ-
ities of the isolated phenolic glycoside isomers.
Disclosure statement
The authors declare no competing financial interest.
Funding
This work was supported by the project Sichuan Science and Technology Poverty Alleviation
[grant number 2016NZYZF] and the project Luzhou Science and Technology [grant number
2
016CDLZ-Z20].
References
Baek SH, Kim DH, Lee CY, Kho YH, Lee CH. 2006. Idescarpin Isolated from the fruits of Idesia
polycarpa inhibits melanin biosynthesis. J Microbiol Biotechn. 16(5):667–672.

NATURAL PRODUCT RESEARCH
5
Chou CJ, Lin LC, Tsai WJ, Hsu SY, Ho LK. 1997. Phenyl b-d-Glucopyranoside derivatives from the
fruits of Idesia polycarpa. J Nat Prod. 60:375–377.
Feistel F, Paetz C, Lorenz S, Beran F, Kunert G, Schneider B. 2017. Idesia polycarpa (Salicaceae)
leaf constituents and their toxic effect on Cerura vinula and Lymantria dispar (Lepidoptera)
larvae. Phytochemistry. 143:170–179.
Jessica T, Claire K, Jo e€ l P, Jeanolivier D, Jacques D. 2009. Comparative antioxidant capacities of
phenolic compounds measured by various tests. Food Chem. 113(4):1226–1233.
John JA, Shahidi F. 2010. Phenolic compounds and antioxidant activity of Brazil nut (Bertholletia
excelsa). J Funct Foods. 2(3):196–209.
Jung MH, Yoo JM, Kang YJ, Lee HW, Kim SH, Sung SH, Lee YJ, Choi I, Kim TJ. 2010. Idesolide, an
isolate of Idesia polycarpa, inhibits apoptosis through induction of intracellular heat shock
protein 70 in C2C12 muscle cells. Biol Pharm Bull. 33(6):1063–1066.
Kim SH, Jang YP, Sung SH, Kim YC. 2007. Inhibitory activity of phenolic glycosides from the
fruits of Idesia polycarpa on Lipopolysaccharide-Induced nitric oxide production in BV2
Microglia. Planta Med. 73(2):167–169.
Kim SH, Sung SH, Choi SY, Chung YK, Kim J, Kim YC. 2005. Idesolide: a new spiro compound
from Idesia polycarpa. Org lett. 7(15):3275–3277.
Kumar M, Rawat P, Khan MF, Tamarkar AK, Srivastava AK, Arya KR, Maurya R. 2010. Phenolic gly-
cosides from Dodecadenia grandiflora and their glucose-6-phosphatase inhibitory activity.
Fitoterapia. 81(6):475–479.
Moritake M, Ueda K, Mori I. 1987. Two phenazine derivatives, polycartine A and B from idesiapo-
lycarpa maxim (flacourtiaceae). Tetrahedron Lett. 28(13):1425–1426.
Vafaei A, Mohamad JB, Karimi E. 2018. HPLC profiling of phenolics and flavonoids of Adonidia
merillii fruits and their antioxidant and cytotoxic properties. Nat Prod Res. 28:1–6.
Yang BY, Chen ZL, Liu Y, Guo JT, Kuang HX. 2018. New lignan from the rattan stems of
Schisandra chinensis. Nat Prod Res. 36:1.
Yang Y, Xiao-Shan T, Fang C, Lin T. 2014. Optimization of phenolics extracted from Idesia poly-
carpa defatted fruit residue and its antioxidant and depigmenting activity in vitro and in vivo.
Evid-Based Compl Alt. 2014(2014):1–12.
Ye Y, Jia RR, Tang L, Chen F. 2014. In Vivo antioxidant and anti-skin-aging activities of Ethyl
Acetate Extraction from Idesia polycarpa defatted fruit residue in aging mice induced by D-
Galactose. Evid-Based Compl Alt. 2014(1):1–12.