全 文 ：
357 Journal of Chinese Pharmaceutical Sciences http://www.jcps.ac.cn
Neuroprotective effects of xanthone extract from Swertia punicea Hemsl
against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced
mouse model of Parkinson’s disease
Yongfei Guo, Chen Wang, Wan Li, Ke Zhang, Hui Lei, Yi Sun, Xiaoping Pu*, Xin Zhao*
Department of Molecular and Cellular Pharmacology; State Key Laboratory of Natural and Biomimetic Drugs, School of
Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
Abstract: As a widely used traditional Chinese medicine (TCM), Swertia punicea Hemsl has exhibited effects on anti-hepatitis
B virus (HBV), liver protection, hypoglycemic activity and cholecystitis. In this study, we confirmed that xanthone extract from
Swertia punicea Hemsl (XSPH) improved the motor deficit, increased the levels of striatal dopamine (DA) and homovanilic acid
(HVA), and alleviated the loss of tyrosine hydroxylase (TH)-positive neurons located in substantia nigra pars compacta
(SNpc) in MPTP-induced mouse model of Parkinson’s disease (PD). In conclusion, the present results indicated that XSPH
offered neuroprotective effects against the neurotoxicity of MPTP and it might be a potential treatment for PD.
Keywords: Xanthone extract from Swertia punicea Hemsl, Parkinson’s disease, MPTP, Dopamine, Homovanilic acid, Tyrosine
hydroxylase
CLC number: R961 Document code: A Article ID: 1003–1057(2016)5–357–09
Received: 2016-02-24, Revised: 2016-03-14, Accepted: 2016-03-29.
Foundation items: National key foundation for exploring scientific
instrument of China (Grant No. 2013YQ030651), National Natural
Science Foundation of China (Grant No. 81202937).
*Corresponding author. Tel.: +86-010-82802431, +86-010-82802648,
E-mail: pxp2020@126.com, zhaoxin2010@bjmu.edu.cn
http://dx.doi.org/10.5246/jcps.2016.05.040
1. Introduction
As a common progressive neurodegenerative disease,
Parkinson’s disease (PD) predominantly affects the
elderly. The incidence of such disease is positively
correlated to age[1]. Clinically, PD leads to a well
known decline of motor functions, including resting
tremor, rigidity, bradykinesia and postural instability
(difficulty with walking and gait)[2,3]. What’s more, some
non-motor-related symptoms, such as olfactory deficits,
depression, cognitive deficits and sleep disorders,
are also included in PD[4,5]. The pathophysiology of
PD results from the progressive and selective loss
of dopaminergic neurons in substantia nigra pars
compacta (SNpc) and striatum[6–8], which leads to
the reduced levels of striatal dopamine (DA) and its
metabolite homovanilic acid (HVA)[9].






As a mitochondrial complex-1 inhibitor, 1-methyl-
4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces
parkinsonian features in various animal models that
closely resemble idiopathic parkinsonism[10,11]. The
C57BL/6 mouse is well known due to its high suscepti-
bility to the neurotoxin. MPTP-induced C57BL/6 mouse
model has been widely used as an in vivo model for
pharmacodynamic study in PD[12–14]. MPTP is converted
to 1-methyl-4-phenylpyridinium (MPP+) by monoamine
oxidase-B (MAO-B), and this oxidative product of
MPTP causes the block of mitochondrial complex I
activity by entering into DA cells via DAT and induces
the loss of dopaminergic neurons[15,16]. Although several
studies have suggested the involvement of oxidative
stress, mitochondrial dysfunction, inflammation and
neuronal loss, the etiologic mechanism of PD is still
obscure[17–20]. The present clinical treatments of PD can
only treat symptoms[21]. None of them can halt or retard
dopaminergic neuron progressive degeneration[22].
Swertia punicea Hemsl (Gentianaceae) is a traditional
Chinese medicine (TCM) with numerous therapeutic
applications. It has satisfactory actions of protecting
liver and anti-HBV in the treatment of chronic hepatitis B,

and it also has hypoglycemic activity[23,24]. In addition,
Swertia punicea Hemsl also plays a role in treating
cholecystitis, fever and jaundice[25,26].
In previous studies, our group found that xanthones
extracted from Swertia punicea Hemsl may have
neuroprotective effects[27]. Therefore, we hypothesized
that xanthone extract from Swertia punicea Hemsl (XSPH)
might have potential therapeutic effects against PD. In
the present study, we investigated the neuroprotective
effects of XSPH based on a MPTP-induced mouse
model of PD.
2. Materials and methods
2.1. Animals and treatment
Male C57BL/6 mice (6–8 weeks, 18–22 g) were
purchased from Charles River Laboratories, Inc. (Beijing,
China) with the confirmation number of SCXK (Jing)
2012–0001. All mice were housed under standard
laboratory conditions with food and water ad libitum.
The room was maintained at a constant temperature
and humidity on a 12-h/12-h light/dark cycle.
A total of 120 C57BL/6 mice were randomly and
evenly divided into six groups as follows: (1) control;
(2) model; (3) selegiline (15 mg/kg/day, S); (4) low
dose of XSPH (4.5 mg/kg/day, L); (5) middle dose of
XSPH (9.0 mg/kg/day, M); (6) high dose of XSPH
(18.0 mg/kg/day, H). Mice in groups (3)–(6) received
selegiline or different doses of XSPH daily for 14 d.
The mice from the control and model groups were
administered with equal volume of normal saline. From
the 10th d of the 14-day experiment period, all groups
except for the control group were intraperitoneally given
MPTP (30 mg/kg/day) 1 h before treated with selegiline or
different doses of XSPH for 5 consecutive days[28]. The
control group was administered with equal volume of
normal saline. All procedures were conducted according
to the guidelines of the Experimental Laboratory Animal
Committee of Peking University and were carried out
in accordance with the principles and guidelines of the
National Institutes of Health Guide for the Care and
Use of Laboratory Animals.
2.2. Materials and reagents
Swertia punicea Hemsl was collected in November
2010 from Dali, Yunnan Province, China, and identified
by Guangxue Liu. A voucher specimen (SP-001) was
deposited in the herbarium of the Department of
Pharmacognosy, School of Pharmaceutical Sciences,
Peking University, Beijing. Swertia punicea Hemsl was
dried, and a weight of 8.4 kg was obtained. Medical
material was crashed to coarse powder and extracted in
10 times of 70% EtOH for three times with an interval of
2 h. Then the filtrates were combined and concentrated
under reduced pressure at 60 °C to a relative density of
1.08–1.10. The collective extract was diluted with
water to 20 L, then filtered and chromatographed on
an AB-8 macropore resin column using gradient elution
with different concentrations of EtOH. The collected
fractions included 30 L of water, 30 L of 30% EtOH,
30 L of 60% EtOH and 10 L of 95% EtOH. The second
fractions of 10 L of 30% EtOH and 60% EtOH were
combined and freeze-dried as the total XSPH (Fig. 1).
To guarantee the quality of the XSPH, HPLC was
applied to detect the contents of two marker ingredients:
1,7-dihydroxy-3,4,8-trimethoxyxanthone and swertianolin.
Experimental apparatus and chromatographic conditions
of HPLC were provided in supplementary material.

358 Guo, Y.F. et al. / J. Chin. Pharm. Sci. 2016, 25 (5), 357–365
Figure 1. The extraction process of XSPH.
Swertia punicea Hemsl (8.4 kg)
Coarse powder
Filtrates
Extract
AB-8 macropore resin column
Each 10 L, including 30-1,2,3 Each 10 L, including 60-1,2,3
Xanthone extract from Swertia punicea Hemsl
Crush
Extracted in 10 times 70% EtOH for
three times with an interval of 2 h.
Filtered and merged
Concentrated under reduced pressure
to a relative density of 1.08–1.10
(60 °C )
Diluted with water to 20 L
Water,
30 L 30% EtOH,
30 L
95% EtOH,
10 L 60% EtOH,
30 L
30-2 60-2

359 Guo, Y.F. et al. / J. Chin. Pharm. Sci. 2016, 25 (5), 357–365
MPTP was purchased from Sigma-Aldrich (Sigma-
Aldrich, St. Louis, USA), and selegiline was purchased
from Orion Corporation (Finland). Primary antibody for
tyrosine hydroxylase (TH, sc-14007) was obtained from
Santa Cruz, Biotechnology (Santa Cruz, CA, USA).
PowervisionTM two-step histostaining reagent (PV-6001)
and DAB Detection Kit (ZIL-9018) were supplied from
Beijing ZhongShan Biotechnology Company.
2.3. General behaviors
General behaviors of the mice were assessed at 20 min
after MPTP administration, including the movement,
breathing, muscle, the response to the external stimula-
tion and other actions[29].
2.4. Locomotor activity
To perform the locomotor activity, mice were placed
in the center of an automated activity chamber (25 cm
in diameter, 13 cm in height) connected to an infrared
tracking analyzer that transmitted the activity data of
mice to a computer on 2nd d after the last dose of
MPTP administration (XZ-4, Institute of Materia
Medica, Chinese Academy of Medical Sciences and
Peking Union Medical College). Mice were allowed
to habituate to the environment for 2 min before
the test, and the numbers of horizontal and vertical
movements were recorded for 5 min by the computer
analyzer[30].
2.5. Rota-rod test
In the rota-rod test, mice were placed on the rota-rod
apparatus for 30 s to adapt (YLS-4C; Ji’nan Yiyan
Science and Technology Development Co., Ltd.). If
dropped, the mice would be put back. Mice were trained
for 2 consecutive days at a fixed speed (12 r/min) before
starting the test. In addition, the rota-rod speed was up
to 35 r/min during the test session. The time spent on
the rota-rod was recorded as the latent period, and the
times that the mice fell down was recorded as falling
times. The test lasted for 180 s. Performance was recorded
as 180 s if the latent period exceeded 180 s. Three tests
per mouse were done with an interval of 30 min, and
the average time was used in further analyses[31].
2.6. Vertical grid test
The vertical grid apparatus was a vertically placed
open box (55 cm×8 cm×5 cm). The back side of box
was a wire mesh (0.6 cm×0.6 cm), and the front side
was open. During the test, mice were placed facing
upward inside the apparatus at 3 cm from the top. Then
the mice turned around and climbed down. The test
was repeated if the mice failed to climb down within
60 s. Three tests per mouse were performed with an
interval of 10 min. Before the test, all the mice were
trained three times a day for 2 consecutive days. Video
was used to record the full test, and then following
parameters were analyzed: time taken to turn (T-turn/s),
time taken to climb down alone (T-A/s) and the average
strides when climbing down (average strides/cm)[32].
2.7. Measurement of striatal DA and HVA levels
using electrochemical HPLC
Six mice of each group were sacrificed, and striatums
were collected to determine the levels of DA and its
metabolite HVA by HPLC[33]. Before the measurement,
the striatum of each mouse was frozen at –80 °C.
Briefly, 1 mg striatum was homogenized in a buffer
containing 0.4 M ice-cold perchloric acid (HClO4), and
the homogenate was centrifuged at 20 000 ×g (4 °C)
for 20 min to precipitate proteins. Its supernatant was
homogenized with 20 mM potassium citrate, 300 mM
dipotassium hydrogen phosphate and 2 mM ethylene-
diamine teraacetic acid disodium salt (EDTA-2Na) in
half volume of the supernatant. Then the homogenate was
centrifuged at 20 000 ×g (4 °C) for 20 min for twice. Its
supernatant was filtrated, and 10–20 μL samples were
injected into a C18 column. The mobile phase consisted
of 85 mM citric acid, 100 mM anhydrous acetic sodium,
0.2 mM ethylenediamine teraacetic acid disodium salt
(EDTA-2Na) and 15% (v/v) methanol (pH 3.68 ) at
a flow rate of 1.2 mL/min. Concentrations of DA and its
metabolites were expressed as μg/g tissue weight.

2.8. TH immunohistochemistry
After the behavioral tests, three mice from each
group were perfused through the aorta with 0.9% saline
followed by cold 4% paraformaldehyde (PFA) under
deep anesthesia. After perfusion, the brain was quickly
removed and post-fixed with 4% PFA for 24 h and
then sequentially incubated in 20% and 30% sucrose
solutions in PBS at 4 °C for 24 h. Then the brain was
cut into 20 µm thick coronal sections through the ventral
mesencephalon with the aid of the mouse brain atlas[34].
Six sections were selected, and all the sections were
matched as closely as possible.
Briefly, the sections were first permeabilized with
0.3% Triton X-100 in PBS at 37 °C for 30 min and
then incubated with 3% hydrogen peroxide (H2O2)
for 1 h at 37 °C to inactivate endogenous peroxidase
activity. Nonspecific adsorption was minimized by
incubating the sections in 10% (v/v) normal goat
serum in PBS at 37 °C for 1 h. After that, sections
were incubated with rabbit anti-TH (1:200, Sigma) at
4 °C overnight. TH-positive neurons were then incubated
with a biotin-labeled secondary antibody at 37 °C for
1 h, and TH immunohistochemistry was performed
using previously published 3,3’-diaminobenzidine (DAB)
protocols[35]. After sealing the slides, images were
obtained on an Olympus microscope (Olympus IX71,
Japan) under the light microscopy, and the number
of TH-immunopositive neurons in the SNpc was calcu-
lated at 400-fold magnification using Image-ProPlus
software. Then the data were expressed as a percentage
of the corresponding area from the intact side (% of
control).
2.9. Statistical analysis
Behavioral and biochemical data were analyzed by
one-way ANOVA followed by Tukey’s test. All data
were expressed as the mean±S.E.M. The results of
immunohistochemical staining were indicated as a ratio
compared with the control group by statistical analysis.
P<0.05 was considered as statistically significant.
3. Results
3.1. Effects of XSPH on behavioral analyses in
MPTP-induced mouse model of PD
3.1.1. General behaviors
Twenty minutes after MPTP administration, the general
behaviors of the mice were observed as tail raised,
piloerection, accelerated breathing and muscle hypotonia
in all groups except for the control group. However,
the reactions of mice from three groups with different
doses of XSPH were slightly different compared with
the model group.
3.1.2. Locomotor activity
In this study, we evaluated motor deficit in the
MPTP-induced PD mice by locomotor activity test.
Compared with the control group, we observed a
significantly decreased number of locomotor movement
in the model group (P<0.001). In addition, compared
with the model group, XSPH treatment (L, M, H)
significantly increased the number of locomotor
movement (P<0.001). The mice treated with selegiline also
demonstrated significant improvements compared with
the model group in terms of the number of locomotor
movement (P<0.001, Fig. 2).
3.1.3. Rota-rod test
After 2 weeks of XSPH treatment, mice from all
groups were assessed for rota-rod behavior. Mice from
the model group showed significant reduction in terms
of latent period and increased falling times compared
360 Guo, Y.F. et al. / J. Chin. Pharm. Sci. 2016, 25 (5), 357–365
Figure 2. Effect on locomotor activity. Data are expressed as
mean±S.E.M (n = 16 each). Vs. control P<0.001###, P<0.01##, P<0.05#;
Vs. Model P<0.001***, P<0.01**, P<0.05*.
180
160
140
120
100
80
60
40
20
0
N
u
m
b
er
s
o
f
m
o
v
e
m
en
ts
/5
m
in

Control Model Sele L M H
###
***
***
***
***

361 Guo, Y.F. et al. / J. Chin. Pharm. Sci. 2016, 25 (5), 357–365
with the control group (P<0.001). Treatment with XSPH
(L, M, H) significantly increased the latent period
(P<0.001, P<0.01) (Fig. 3A) and decreased the falling
times compared with the model group (P<0.001)
(Fig. 3B).
3.1.4. Vertical grid test
The vertical grid test showed that MPTP caused a
pronounced increase in time taken to turn (T-turn/s),
time taken to climb down alone (T-A/s) and a decrease
in the average strides when climbing down (average
strides/cm, P<0.001). In T-turn part, XSPH treatments
in L (P<0.05), M (P<0.01) and H (P<0.01) doses
significantly decreased the T-turn (Fig. 4A). In T-A part,
mice in L (P<0.01), M (P<0.01) and H groups (P<0.05)
showed the significantly decreased T-A (Fig. 4B).
Mice treated with XSPH also showed the significantly
increased average strides in L (P<0.001), M (P<0.001)
and H groups (P<0.01) (Fig. 4C).
3.2. Effects of XSPH on striatal DA and HVA levels
in MPTP-induced mouse model of PD
Mice from the model group showed a substantial









diminution of DA (P<0.01) and HVA (P<0.001) in striatal
tissue compared with the control group. The reductions of
DA and HVA were attenuated when the mice were treated
with XSPH. Mice treated with XSPH in L (P<0.05),
M (P<0.05) and H groups (P<0.01) showed significantly
enhanced levels of striatal DA compared with the model
group. Mice treated with XSPH in L (P<0.05) and H groups
(P<0.01) showed significantly enhanced levels of striatal
HVA compared with the model group (Fig. 5).
3.3. Effects of XSPH on TH-positive neurons in the
SNpc in MPTP-induced mouse model of PD.
Immunohistochemical staining was used to measure
Figure 3. (A) Latent period of mice on rota-rod test; (B) Falling
numbers of mice on rota-rod test. Data are expressed as mean±S.E.M
(n = 10 each). Vs. control P<0.001###, P<0.01##, P<0.05#; Vs. Model
P<0.001***, P<0.01**, P<0.05*.
140
120
100
80
60
40
20
0
L
at
en
t
p
er
io
d
(
s)

Control Model Sele L M H
###
***
*** *** **
(A)
10
9
8
7
6
5
4
3
2
1
0
F
al
li
n
g
n
u
m
b
er
s
Control Model Sele L M H
###
***
***
***
***
(B)
Figure 4. (A) Time taken to make the turn (T-turn/s) of mice on
vertical grid test. (B) Time taken to climb down alone (T-A/s) of
mice on vertical grid test. (C) Average strides of mice on vertical grid
test. Data are expressed as mean±S.E.M (n = 10 each). Vs. control
P<0.001###, P<0.01##, P<0.05#; Vs. Model P<0.001***, P<0.01**,
P<0.05*.
4.5
4.0
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
T
-t
u
rn
(
s)

Control Model Sele L M H
###
**
*
**
**
(A)
10
9
8
7
6
5
4
3
2
1
0
T
-A
(
s)

Control Model Sele L M H
### (B)
** ** **
*
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0
A
v
er
ag
e
st
ri
d
es
(
cm
)
Control Model Sele L M H
###
(C)
***
***
***
**











































the level of TH-positive neurons in the SNpc. Compared
with the control group, the TH-immunoreactive neurons
were significantly reduced by MPTP exposure in
the model group. Treatment with XSPH significantly
halted the reductions of TH-positive neurons (Fig. 6A).
Quantitative analysis indicated that the number of
TH-positive neurons in the model group was signifi-
cantly lower than that of the control group (P<0.001).
Mice treated with XSPH in L (P<0.01), M (P<0.001)
and H groups (P<0.001) showed significantly inhibited loss
of TH-positive neurons compared with the model group
(Fig. 6B). This result suggested that XSPH significantly
protected against MPTP-induced reduction in TH-positive
neurons in the SNpc.
4. Discussion
PD is a multi-factorial disease triggered by multiple
pathogenic factors[19]. Repeated exposure to environ-
mental toxic reagents, such as MPTP, may be a reason for
PD[36]. The complicated pathogenetic mechanisms lead to
the difficulties on the drug development of PD treatment.
In this study, we investigated the neuroprotective effects
of XSPH in MPTP-induced mouse model of PD.
C57BL/6 mice intoxicated with parkinsonian neuro-
toxin MPTP show deficiencies in behavioral activities[37].
In our present study, we evaluated the motor deficit of
PD mice by observation of general behaviors, locomotor
activity test, rota-rod test and vertical grid test. The
general behaviors of the mice included tail raised,
piloerection, accelerated breathing and muscle hypotonia
after MPTP administration, while treatment with XSPH
alleviated this motor deficit. Locomotor activity test is
a commonly used method in neuropharmacology drug
research[38]. Our finding indicated that different doses
of XSPH (L, M, H) effectively increased the number of
locomotor movement. The rota-rod test is also widely
applied to evaluate MPTP-induced PD models[39].
Compared with the control group, the latent period was
reduced, and the falling number was significantly
increased in the model group. However, these indexes
were obviously improved in mice treated with different
362 Guo, Y.F. et al. / J. Chin. Pharm. Sci. 2016, 25 (5), 357–365
Figure 5. Striatal contents in μg/g tissue of DA and HVA measured by
HPLC with ECD system. Data are expressed as mean±S.E.M (n = 6 each).
Vs. control P<0.001###, P<0.01##, P<0.05#; Vs. Model P<0.001***,
P<0.01**, P<0.05*.
Figure 6. (A) TH-positive neurons in the SNpc. Representative
photographs showing the appearance of the dopaminergic neurons
at a magnification of 400×. (B) Quantitative analysis of TH positive
neurons in the SNpc at a magnification of 400×. Data are expressed as
mean±S.E.M (n = 3 and 6 sections per mice). Vs. control P<0.001###,
P<0.01##, P<0.05#; Vs. Model P<0.001***, P<0.01**, P<0.05*.
20.00


15.00


10.00


5.00


0.00
μ
g
/g
o
f
ti
ss
u
e
Control Model Sele L M H
###
***
*
* **
##
*** * **
DA
HVA
120

100

80

60

40

20

0
T
H
p
o
si
ti
v
e
n
eu
ro
n
s

(%
o
f
th
e
co
n
tr
o
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Control Model Sele L M H
###
***
**
***
***
(B)
Control Model




S L




M H
(A)

363 Guo, Y.F. et al. / J. Chin. Pharm. Sci. 2016, 25 (5), 357–365
doses of XSPH (L, M, H). The vertical grid test can
provide a sensitive measure of motor deficit in mice
following MPTP administration[40]. The results of T-turn,
T-A and average strides indicated that the deficiencies
in behavioral activities were significantly ameliorated
in mice treated with XSPH (L, M, H).
TH is the rate-limiting enzyme in the biosynthesis of DA
and TH protein, which is decreased in the nigrostriatal DA
neurons of PD patients[41]. MPTP administration to
C57BL mice leads to a decline of striatal DA and TH
levels in the SNpc[42]. DA is metabolized HVA, and the
contents of DA and its metabolite HVA in the striatum
are decreased with MPTP administration[43,44]. In order
to further verify the neuroprotective effects of XSPH,
we measured the levels of striatal DA and its metabolite
HVA by HPLC and TH-positive neurons in the SNpc by
immunohistochemistry. In the present study, we found
that the MPTP-induced PD mice showed a significant
decrease in the contents of DA and HVA. Mice treated
with XSPH showed significantly increased contents of
DA (L, M, H) and HVA (L, H). In addition, our results
from immunohistochemistry confirmed that MPTP-induced
PD mice had reduced TH-positive neurons in the SNpc,
which was in accordance with the previous record[42].
We also established that XSPH treatment significantly
prevented the loss of TH-positive neurons in the SNpc
induced by MPTP, which was visually reflected by
the photographs. The data also demonstrated that the
number of TH-positive neurons in the SNpc was decreased
in MPTP-induced PD mice, but such a reduction was
significantly elevated by XSPH treatment (L, M, H).
The result of TH-positive neurons by immunohisto-
chemistry showed that XSPH treatment (M) was more
effective than other treatments, and similar findings
were observed in behavioral tests. These were different
from the data of striatal DA and its metabolite HVA by
HPLC, which showed that XSPH treatment (H) was
more effective. Because of the individual differences
among all mice, different mice treated with different
doses of XSPH (L, M, H) might have different drug
reactions. What’s more, the pathologic changes of PD
include the degeneration of DA neurons in the SNpc,
the depletion of striatal DA and the occurrence of
Lewy body (LB) in the SNpc. However, the two most
characteristic pathologic hallmarks of PD are the
degeneration of DA neurons and the occurrence of LB
in the SNpc[45]. The recorded experiments showed that
PD develops when the content of DA neurons in the
SNpc is decreased by 60%–80% and the striatal DA
drops to 30% of normal[46,47]. It also confirmed the
degeneration of DA neurons in the SNpc was even
more remarkable in the process of PD. The results of
TH-positive neurons by immunohistochemistry and
behavioral tests verified the consistency. Furthermore,
different doses of XSPH treatment (L, M, H) might
have different pharmacodynamic actions aimed at
different parts of the brain.
According to the above-mentioned results, we found
that XSPH significantly improved the abnormal motor
deficit caused by MPTP, increased the contents of
DA and HVA in the striatum and also inhibited the
reduction of TH-positive neurons in the SNpc. All
these results suggested that treatment with XSPH had
neuroprotective effects against MPTP-induced mouse
model of PD. Even though the neuroprotective mechanism
of XSPH remains unclear, it is likely that XSPH may
be used as potential neuroprotective agent to halt the
progression of PD. However, further research and
clinical studies are still needed.
Acknowledgements
This work was supported by grants from the National
key foundation for exploring scientific instrument of
China (Grant No. 2013YQ030651) and National Natural
Science Foundation of China (Grant No. 81202937).
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365 Guo, Y.F. et al. / J. Chin. Pharm. Sci. 2016, 25 (5), 357–365
紫红獐牙菜 酮提取物对MPTP所致的帕金森小鼠的神经保护作用
郭涌斐, 王辰, 李婉, 张珂, 雷慧, 孙懿, 蒲小平*, 赵欣*
北京大学医学部 药学院 分子与细胞药理学系; 天然药物及仿生药物国家重点实验室, 北京 100191
摘要: 紫红獐牙菜提取物是一种应用广泛的中国传统中药, 其抗乙型肝炎病毒, 保肝, 降低血糖等作用已经被报道。
在本研究中, 我们发现紫红獐牙菜 酮提取物可以改善1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森(PD)小鼠的
运动功能障碍。此外, 我们还发现该提取物能够提高纹状体中多巴胺(DA)和高香草酸(HVA)的含量, 缓解由于MPTP导致
的黑质致密区的酪氨酸羟化酶(TH)阳性神经元的缺失。这些结果表明, 紫红獐牙菜 酮提取物具有对抗MPTP神经毒素
的神经保护作用, 有望成为一个潜在的治疗帕金森病的药物。
关键词: 紫红獐牙菜 酮提取物; 帕金森病; 1-甲基-4-苯基-1,2,3,6-四氢吡啶; 多巴胺; 高香草酸; 酪氨酸羟化酶
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