Lignans and phenylpropanoids from the roots of Ficus hirta and their cytotoxic activities

Article abstract of DOI:10.1080/14786419.2021.1892099

One undescribed lignan, one new natural product, along with fourteen known compounds, were isolated from the roots of Ficus hirta. The structures of the isolates were elucidated by comprehensive spectroscopic technologies, including UV, IR, HRESIMS, and NMR. The absolute configuration of 1 was determined by comparison of experimental and calculated ECD data. The cytotoxicity of all the compounds against HeLa and HepG2 cell lines was evaluated and compound 7 showed considerable cytotoxic effect towards HepG2 cells. Also, the apoptotic effect of 7 on HepG2 cells and the effect of 7 on the key proteins (p-JNK and p-p38) in MAPK (Mitogen-activated protein kinases) pathways were studied by flow cytometry and western blotting experiment. As a result, compound 7 induced the apoptosis of HepG2 cells, and dose-dependently increased the phosphorylation of JNK and p38. Thus, 7 might trigger HepG2 cells apoptosis via JNK/p38 MAPK signaling pathway.

Full text of DOI:10.1080/14786419.2021.1892099

Natural Product Research
Formerly Natural Product Letters
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gnpl20
Lignans and phenylpropanoids from the roots of
Ficus hirta and their cytotoxic activities
Xian-Sheng Ye, Wen-Jing Tian, Xiang-Zhong Liu, Mi Zhou, De-Quan Zeng, Ting
Lin, Guang-Hui Wang, Xin-Sheng Yao & Hai-Feng Chen
To cite this article: Xian-Sheng Ye, Wen-Jing Tian, Xiang-Zhong Liu, Mi Zhou, De-Quan
Zeng, Ting Lin, Guang-Hui Wang, Xin-Sheng Yao & Hai-Feng Chen (2021): Lignans and
phenylpropanoids from the roots of Ficusꢀhirta and their cytotoxic activities, Natural Product
Research, DOI: 10.1080/14786419.2021.1892099
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NATURAL PRODUCT RESEARCH
https://doi.org/10.1080/14786419.2021.1892099
Lignans and phenylpropanoids from the roots of Ficus
hirta and their cytotoxic activities
Xian-Sheng Yea, Wen-Jing Tiana, Xiang-Zhong Liua, Mi Zhoua, De-Quan Zenga,
Ting Lina, Guang-Hui Wanga, Xin-Sheng Yaoa,b and Hai-Feng Chena
aFujian Provincial Key Laboratory of Innovative Drug Target, School of Pharmaceutical Sciences,
b
Xiamen University, Xiamen, People’s Republic of China; Institute of Traditional Chinese Medicine &
Natural Products, Jinan University, Guangzhou, People’s Republic of China
ABSTRACT
ARTICLE HISTORY
Received 25 November 2020
Accepted 14 February 2021
One undescribed lignan, one new natural product, along with
fourteen known compounds, were isolated from the roots of Ficus
hirta. The structures of the isolates were elucidated by compre-
hensive spectroscopic technologies, including UV, IR, HRESIMS,
and NMR. The absolute configuration of 1 was determined by
comparison of experimental and calculated ECD data. The cyto-
toxicity of all the compounds against HeLa and HepG2 cell lines
was evaluated and compound 7 showed considerable cytotoxic
effect towards HepG2 cells. Also, the apoptotic effect of 7 on
HepG2 cells and the effect of 7 on the key proteins (p-JNK and p-
p38) in MAPK (Mitogen-activated protein kinases) pathways were
studied by flow cytometry and western blotting experiment. As a
result, compound 7 induced the apoptosis of HepG2 cells, and
dose-dependently increased the phosphorylation of JNK and p38.
Thus, 7 might trigger HepG2 cells apoptosis via JNK/p38 MAPK
signaling pathway.
KEYWORDS
Ficus hirta; cytotoxic
activity; apoptosis; JNK;
p38 MAPK
CONTACT Xin-Sheng Yao
These authors contributed equally to this work.
tyaoxs@jnu.edu.cn; Hai-Feng Chen
haifeng@xmu.edu.cn
ꢀ
Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2021.1892099.
ß 2021 Informa UK Limited, trading as Taylor & Francis Group

2
X.-S. YE ET AL.
1. Introduction
In recent years, cancer remains one of the most dangerous diseases with a high fatal-
ity rate. Finding new chemotherapeutic agents inducing apoptosis of tumor cells is
considered one of the most effective strategies for the treatment of cancer. Natural
products play an essential role in the development of anticancer drugs. Therefore, it is
of great significance to find potential anticancer agents from traditional
Chinese medicine.
The pathological progress of tumor cell apoptosis is regulated by several signaling
pathways. JNK (c-Jun N-terminal kinase) and p38 are the key proteins in MAPK
(Mitogen-activated protein kinases) signaling pathways, which play crucial roles in the
development of cancer, including cell growth, proliferation, and apoptosis (Sui et al.
2014; Kim et al. 2019; He et al. 2020).
Ficus hirta Vahl. (Wuzhimaotao), belonging to the Moraceae family is widely distrib-
uted in the south of China, such as Yunnan, Guangdong, and Fujian provinces. The
roots of F. hirta were folk medicine for the treatment of cough, hepatitis, rheumatism,
edema, and fatigue. Recent pharmacological studies revealed that F. hirta possessed
antitumor, hepatoprotective, antibacterial, and anti-inflammatory effects (Qu et al.
2003; Chen et al. 2012; Zeng et al. 2012; Wan et al. 2016; Cai et al. 2017; Yang et al.
2018; Ye et al. 2020). Chemical studies have reported that a series of phenylpropa-
noids, flavonoids, coumarins, triterpenoids, and phenolic acids have been isolated
from the root of F. hirta (Ya et al. 2010; Cheng et al. 2017a; 2017b; Ye et al. 2020).
Also, lignans are the important source of natural products and exhibit a variety of bio-
ꢀ ꢁꢀ
logical activities (Tomassini et al. 2018; Zalesak et al. 2019; Frezza et al. 2020). In this
paper, the phytochemical study on F. hirta led to the isolation of 16 lignans and sim-
ple phenylpropanoids (Figure 1), including one undescribed lignan (1) and one new
natural product (7). All compounds were tested for their cytotoxicity against Hela and

NATURAL PRODUCT RESEARCH
3
Figure 1. Structures of compounds 1 2 16 isolated from the roots of F. hirta.
HepG2 cell lines in vitro. Besides, the apoptotic effect of 7 on HepG2 cells and the
effect of 7 on the crucial proteins (p-JNK and p-p38) in the MAPK signaling pathways
were evaluated.
2. Results and discussion
Compound 1, obtained as a white amorphous powder. Its molecular formula of
C28H36O13 was determined by the positive HRESIMS data (m/z 603.2043 [M þ Na]þ,
1
calcd 603.2048). The H NMR spectrum (Table S1) of 1 showed three aromatic proton
signals at dH 6.35 (2H, s) and 6.79 (1H, s). Moreover, four methines groups [dH 2.41
(1H, m), dH 2.94 (1H, m), 4.16 (1H, overlaps), and 4.87 (1H, overlaps)] and four methoxy
groups [(dH 3.69 (3H, s), 3.77 (6H, s) and 3.94 (3H, s)] were observed. The 13C NMR
spectra (Table S1) exhibited 28 carbon resonances due to two methylenes, four

4
X.-S. YE ET AL.
methines, four methoxy, twelve aromatic carbons, and a glucose group. Careful ana-
lysis of the NMR data of 1 suggested that it was similar to cissuside (Kumar et al.
2019) except for the differences of substituent groups in phenyl ring, the substituent
location of glucose group, and the chemical shift of C-7 (1: dC 80.4; cissuside: dC 33.8).
After acid hydrolysis, the sugar unit of 1 was identified as D-glucose (18.03 min) by
HPLC analysis. The HMBC correlations (Figure S2) from dH 6.79 to C-7/C-4/C-5, dH 3.69
to C-5, and dH 3.94 to C-3 confirmed the presence of the 3, 5-dimethoxyphenyl ring.
Furthermore, the HMBC correlation (Figure S2) from H-1000 to C-4 indicated that the
sugar moiety was located at C-4. The chemical shift of C-7 and the molecular formula
of C28H36O13 suggested that a hydroxyl was connected to C-7. The coupling constant
of J7 ,8 (1.8 Hz) implied that H-70 was cis-oriented with H-80 (Liu et al. 2015), which was
further confirmed by the NOESY correlation of H-70 and H-80. Also, The NOESY cross-
peaks (Figure S3) of H-70/H-7 and H-70/H-8 implied that H-7, H-8, H-70, and H-80 had
the same orientation. Accordingly, the planar structure of 1 was established. The abso-
lute configuration of 1 was determined by comparison of experimental and calculated
ECD data. As shown in figure S4, the calculated ECD spectrum of (7 R, 8S, 70R, 80R)-1a
was agreed with the experimental spectrum of 1. Thus, the absolute configuration of
1 was determined and compound 1 was named ficuslignin A.
0
0
Compound 7, obtained as a white amorphous powder. Its molecular formula of
C33H38O13 was determined by the positive HRESIMS data (m/z 643.2385 [M þ H]þ,
1
calcd 643.2378). The H NMR spectrum (Table S1) of 7 showed six aromatic proton sig-
nals at dH 7.36 (1H, s), 7.35 (1H, s), 6.68 (2H, s) and 6.65 (2H, s), together with six
methoxy groups at dH 3.85 (6H, s), 3.84 (6H, s), and 3.72 (6H, s). The 13C NMR spectra
(Table S1) exhibited 33 carbon resonances, including three aromatic rings. According
to 1 D NMR and HSQC spectra, two sets of similar signals at 4.71 (87.6), 3.13 (55.5),
3.95/4.27 (72.9), and 4.75 (87.2), 3.12 (55.7), 3.90/4.27 (72.8) indicated the presence of
a typical skeleton of ditetrahydrofuran. A further detailed analysis of NMR spectra
showed that compound 7 had the similar planar structure to (-)-(7 R,7’R,70’S,8S,8’S,80’S)-
40,40’-dihydroxy-3,30,30’,5,50, 50’-hexamethoxy-7,90:70,9-diepoxy-4,80’-oxy-8,80-sesquineoli-
gnan-70’,90’-diol except for the significant downshift of C-700 (dC 197.3) (Xiong et al.
2011). Furthermore, the HMBC correlations from H-800/900 to C-700 indicated that C-700
was substituted by a carbonyl (Figure S2). The coupling constants of J7,8 (4.0 Hz) and
J7 ,8 (4.0 Hz), together with the chemical shifts of H-7/H-70 (4.71/4.75), H-8/H-80 (3.13/
3.12), C-7/C-70 (87.6/87.2), and C-8/C-80 (55.5/55.7), proved the cis-relationship of two
aryl groups with H-8 and H-80, respectively (Kamaya et al. 1983; Kim et al. 2010). The
H-7/H-8 trans and H-70/H-80 trans configurations of 7 were further confirmed by the
0
0
0
values of DdH-9 (0.39 ppm) and DdH-9 (0.37 ppm) (Shao et al. 2018). The absolute con-
figuration of ditetrahydrofuran moiety in 7 was characterized as 7 R,8S,70R,80S by com-
parison of experiment ECD spectrum and that of known compound (Kim et al. 2010)
(a strong positive cotton effect at 208 nm (Figure S28) matched well with colocasinol
A). Compound 7 was previously described as a synthetic product without any NMR
and MS data (Kamaya et al. 1983). We herein reported it as a natural product for the
first time and it was named ficuslignin B.
In addition, 14 known compounds were isolated from the roots of F. hirta. These
compounds were identified as (þ)-lyoniresinol (2) (Wang et al. 2013), leptolepisol D (3)

NATURAL PRODUCT RESEARCH
5
(Zhu et al. 2012), (þ)-syringaresinol (4) (Wang et al. 2009), lirioresinol A (5) (Xu et al.
2014), hedyotol C (6) (Liao et al. 2014), (-)-(7 R,7’R,70’R,8S,8’S,80’S)-40,40’-Dihydroxy-
3,30,30’,5,50-pentamethoxy-7,90:70,9-diepoxy-4,80’-oxy-8,80-sesquineolignan-70’,90’-diol (8)
(Xiong et al. 2011), (þ)-(7 R,7’R,70’R,70’’S,8S,8’S,80’S,80’’S)-40’,40’’-Dihydroxy-3,30,30’,30’’,5,50-
hexamethoxy-7,90:70,9-diepoxy-4,80’:40,80’’-bisoxy-8,80-dineolignan-70’,70’’,90’,90’’-tetraol (9)
(Xiong et al. 2011), salicifoliol (10) (Liu et al. 2013), zhepeiresinol (11) (Jin et al. 1993),
eythero-2,3-bis-(4-hydroxy-3-methoxypheyl)-3-methoxypropanol (12) (Yang et al. 2018),
thero-2,3-bis-(4-hydroxy-3-methoxypheyl)-3-methoxypropanol (13) (Yang et al. 2018),
ficuscarpanoside A (14) (Wang et al. 2017), ficuscarpanoside B (15) (Ouyang and Kuo
2006), evofolin B (16) (Duan et al. 2009).
The cytotoxicity of the isolates against Hela and HepG2 cell lines was evaluated by
MTT assay. The result showed that compound 7 had distinct cytotoxicity against
HepG2 cells at a concentration of 30 mM (Figure S5) and the IC50 value is 31.52 lM
(Table S2). Subsequently, the apoptotic effect of 7 on HepG2 cells was detected by
flow cytometry. As shown in figure S6, 7 induced the cells apoptosis from 6.64% to
12.06% after treated with gradient concentrations of 7 (0, 10, 20, 30 mM). MAPK signal-
ing pathways have been reported to play a vital role in the apoptosis of tumor cells
(Tsay et al. 2009; Ju et al. 2013; Hsieh et al. 2017; Xie et al. 2016; Zhu et al. 2016; Lin
et al. 2018; Ham et al. 2019; Jiang et al. 2019). Evidences proved that the phosphoryl-
ation levels of JNK and p38 were up-regulated when treated with small molecules reg-
ulating these signaling pathways (Hsieh et al. 2017; Lin et al. 2018; Ham et al. 2019;
Jiang et al. 2019). In this study, the effect of 7 on the MAPK pathway was investigated
by western blot assay. As shown in figure S7, compound 7 markedly increased the
expression levels of p-JNK and p-p38.
Compound 7 possessed a similar structure with 6, 8, and 9, except for the extra
carbonyl group. Compound 7 showed more potent antitumor activity than the others.
Preliminary structure ꢁ activity relationship (SAR) analysis revealed that the carbonyl
group at C-7 was essential for the antitumor activity.
3. Experimental
3.1. General experimental procedures
Optical rotations were measured on a P-2000 polarimeter at 20 ꢂC (JASCO, Japan). UV
spectra were obtained using a Shimadzu UV-2600 spectrometer (Shimadzu, Japan). IR
spectra were acquired by a Nicolet iS50 spectrometer (Thermo Scientific, USA). ECD
spectra were measured on a MOS-500 circular dichroism spectrometer (Bio-Logic,
France). The NMR and HRESIMS experiments were performed on a Bruker Avance III
600 MHz spectrometer (Bruker, Germany) and a Thermo Q Exactive Orbitrap mass
spectrometer (Thermo Scientific, USA). Preparative and semi-preparative HPLC were
performed on LC-16P instrument equipped with SPD-M20A detector (Shimadzu,
Japan). D101 macroporous resin (CangZhou Bon Adsorber Technology Company), silica
gel (200-300 mesh, Qingdao Ocean Chemical Company), Sephadex LH-20
(18 ꢁ 110 lm, Pharmacia), and YMC ODS-A (50 lm) were applied to column
chromatography.

6
X.-S. YE ET AL.
3.2. Plant material
The dried roots of F. hirta were purchased from Quanzhou city, Fujian province,
People’s Republic of China, in February 2017. The plant materials were identified
by Prof. Zhen-Ji Li (College of the Environment & Ecology, Xiamen University). A
voucher specimen (Fh-20170202) was deposited at Fujian Provincial Key
Laboratory of Innovative Drug Target, School of Pharmaceutical Sciences,
Xiamen University.
3.3. Extraction and isolation
The dried roots of F. hirta were extracted three times with 60% ethanol, and then con-
centrated in a vacuum to yield a residue. The crude extract was suspended in water
and then subjected to chromatography on a D101 macroporous resin column eluted
with H2O-ethanol (0, 30%, 55% and 59%). The 30% ethanol residue (fraction B) (650 g)
was separated by silica gel chromatography eluted with PE-EtOAc (3:1 to 0:1) and
CH2Cl2ꢁMeOH (9:1 to 0:1) to obtain 4 fractions (B1 ꢁ B4). Fraction B1 (70.0 g) was
chromatographed over Sephadex LH-20 column eluted with MeOH to yield 5 subfrac-
tions (B1.1-B1.5). Fraction B1.2 (22.0 g) was separated on an ODS CC eluted with
MeOH ꢁ H2O (8:92 to 60:40) to give 5 fractions (B1.2.1 ꢁ B1.2.5). Fraction B1.2.1
(500 mg) was purified by semi-preparative HPLC (ACN ꢁ H2O, 10:90, 2.0 ml/min) to
afford compound 3 (1.5 mg, tR ¼ 61.0 min). Fraction B1.2.2 (300 mg) was purified by
semi-preparative HPLC (MeOH ꢁ H2O, 25:75, 3.0 ml/min) to obtain compounds 2
(6.5 mg, tR ¼ 32.5 min), 12 (25.0 mg, tR ¼ 33.0 min), and 13 (25.0 mg, tR ¼ 33.3 min).
Fraction B1.2.3 (5.0 g) was further separated by semi-preparative HPLC (ACN ꢁ H2O,
10:90, 3.0 ml/min) to yield compounds 1 (9.0 mg, tR ¼ 55.0 min), 14 (8.3 mg, tR
¼
13.5 min), and 15 (7.0 mg, tR ¼ 14.0 min). The 55% ethanol residue (fraction C) (308 g)
was separated by silica gel chromatography eluted with PE-EtOAc (3:1 to 0:1) and
CH2Cl2ꢁMeOH (9:1 to 0:1) to give 8 fractions (C1 ꢁ C7). Fraction C1 (20 g) was purified
by ODS CC eluted with MeOH ꢁ H2O (20:80 to 100:0) to obtain 6 fractions
(C1.1 ꢁ C1.6). Fraction C1.1 (200 mg) was further purified by semi-preparative HPLC
(ACN ꢁ H2O, 45:55, 3.0 ml/min) to give compounds 10 (2.6 mg, tR ¼ 24.0 min), 11
(2.6 mg, tR ¼ 24.3 min), and 16 (20.0 mg, tR ¼ 33.0 min). Fraction C1.2 (6.0 g) was sub-
jected to ODS CC eluted with MeOH ꢁ H2O (20:80 to 65:40) to afford 4 fractions
(C1.2.1 ꢁ C1.2.3). Fraction C1.2.2 (1.0 g) was purified by a Sephadex LH-20 column
eluted with CH2Cl2-MeOH (1:1) to yield 4 subfractions (C1.2.2.1-C1.2.2.4). Fraction
C1.2.2.2 (120 mg) was purified by semi-preparative HPLC (ACN ꢁ H2O, 30:70, 3.0 ml/
min) to yield compounds 4 (14.0 mg, tR ¼ 21.7 min), 5 (2.0 mg, tR ¼ 28.0 min), 6
(1.5 mg, tR ¼ 41.8 min), 7 (1.0 mg, tR ¼ 43.8 min), 8 (3.0 mg, tR ¼ 37.1 min) and 9
(3.0 mg, tR ¼ 50.0 min).
Ficuslignin A (1). White, amorphous powder; [a]2D0-36 (c 0.10, MeOH); ECD (MeOH)
kmax (De) 205 (þ5.98), 217 (-6.15), 242 (þ0.59) nm; UV (MeOH) kmax (log e) 209 (4.40)
1
nm, 242 (3.46) nm; IR (KBr) ꢀmax 3420, 2900, 1609, 1517, 1457, 1215, 1111 cmꢁ1; H
and 13C NMR data, see Table S1; HRESIMS m/z 603.2043 [M þ Na]þ (calcd for
C28H36O13Na, 603.2048)。

NATURAL PRODUCT RESEARCH
7
Ficuslignin B (7). White, amorphous powder; [a]2D0-10 (c 0.10, MeOH); UV (MeOH)
kmax (log e) 203 (-4.17) nm, 208 (þ5.29) nm, 214 (-4.72) nm, 219 (þ0.51) nm, 225
1
(þ2.40) nm; IR (KBr) ꢀmax 3395, 2938, 2854, 1668, 1600, 1514, 1118 cmꢁ1; H and 13C
NMR data, see Table S1; HRESIMS m/z 643.2378 [M þ H]þ (calcd for
C33H39O13, 643.2385).
3.4. ECD calculation method
In general, conformational analyses were carried out via random searching in the
Sybyl-X 2.0 using the MMFF94S force field with an energy cutoff of 3.0 kcal/mol.
The conformers were re-optimized using DFT at the b3lyp/6-311 þ g(2d,p) level in
the gas phase by the GAUSSIAN 09 program. The energies, oscillator strengths, and
rotational strengths (velocity) of the first 60 electronic excitations were calculated
using the TDDFT methodology at the b3lyp/6-311þþg(2d,p) level in methanol. The
ECD spectra were simulated by the overlapping Gaussian function (half the band-
width at 1/e peak height, r ¼ 0.3). The simulated spectra of the conformers were
averaged by the Boltzmann distribution theory to obtain the final calculated
ECD spectrum.
3.5. Cell culture
HeLa and HepG2 cell lines were cultured in Dulbecco’s modified Eagle’s medium
(DMEM) with 10% FBS, 100 U/mL penicillin, and 100 mg/mL streptomycin, and incu-
bated at 37 ꢂC in a humidified atmosphere containing 5% CO2.
3.6. Screening for cytotoxicity
The cytotoxicity of compounds 1-16 (30 lM) against HeLa and HepG2 cell lines were
screened by MTT test. Briefly, the good growing cells were seeded in 96-well plates
and incubated overnight, then treated with positive drug (cisplatin 10 lM) or com-
pounds (30 lM) for 24 h. Cells were further incubated with MTT (3-(4,5-dimethylthiazol-
2-yl)-2,5-diphenyltetrazolium bromide) for 4 h at 37 ꢂC. When the cell supernatants
were removed, the crystals were dissolved in DMSO. Finally, the absorbance of the
solution was measured at 490 nm on a microplate reader.
3.7. Detection of apoptotic cells by double staining
The apoptotic cells were detected using annexin V-FITC/propidium iodide (PI) double
staining apoptosis detection kit (Vazyme, Nanjing, China). Hela cells were seeded in 6-
well plates and incubated with various concentrations (0, 10, 20, 30, 40 lM) of com-
pound 7 for 24 h. Then, the cells were collected and washed twice with PBS at 4 ꢂC,
resuspended in 100 lL of binding buffer containing 5 lL of annexin V and 5 lL of PI in
the dark for 10 min. After that, a 400 lL binding buffer was added. Finally, early or late
apoptosis was detected by a flow cytometer (Invitrogen Attune NxT, Thermo Fisher
Scientific, USA).

8
X.-S. YE ET AL.
3.8. Western blot analysis
Hela cells were cultured in 6-well plates overnight and then various concentrations of
compound 7 (10, 20, 30 lM) were added in for 24 h. After that, cells were treated with
RIPA buffer containing protease and phosphatase inhibitors. Proteins were quantified
by BCA protein assay kit (Beyotime, China). Subsequently, the equal amounts of pro-
teins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis
(SDS-PAGE), transferred onto PVDF membranes (Millipore, USA), and blocked with skim
milk for 1 h. After washing in TBST three times, the membranes were incubated with
primary antibodies: p-JNK1/2 (Thr183/Tyr185), p-p38 MAPK (Thr180/Tyr182), JNK1/2,
p38 MAPK, and GADPH (1:2000 dilution) at 4 ꢂC overnight. The membranes were
washed by TBST three times again before incubated with secondary antibodies
(1:3000 dilution) for 1 h at room temperature. Finally, the immunoreactivity of mem-
branes was detected using an ECL kit (WesternBright ECL, Advansta, USA).
4. Conclusion
In conclusion, one undescribed lignan and one new natural product, together with
fourteen known compounds were isolated from the roots of F. hirta. Compound 7
showed a considerable cytotoxic effect on HepG2 cells. Besides, the apoptotic effect of
7 on HepG2 cells and the effects of 7 on the key proteins (p-JNK and p-p38) of MAPK
pathways were studied by flow cytometry and western blotting experiment. As a
result, compound 7 induced the apoptosis of HepG2 cells, and dose-dependently
increased the phosphorylation of JNK and p38. Thus, 7 might trigger HepG2 cells
apoptosis via JNK/p38 related MAPK signaling pathway. And 7 might be considered as
a potential lead for the development of anticancer drugs.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by grants from the Natural Science Foundation of China (NSFC) (Nos.
81773866, 81771377 and U1705285), Fundamental Research Funds for the Central Universities
(No.20720190079) and Natural Science Foundation of Fujian Province of China (No.2019J007).
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