X Use of Angong Niuhuang in Treating Central Nervous System Diseases and Related Research

Abstract

In Chinese medicine-based therapeutics, Angong Niuhuang pill (ANP) is one of the three most effective formulas for febrile diseases, and it is also used to treat other diseases. This paper reviews current knowledge regarding the clinical and pharmacological effects of ANP for treating different central nervous system (CNS) diseases to confirm its validity and efficacy. These diseases are like centric fever, coma, stroke, and viral encephalitis. This review reveals that various diseases could be treated using the same agent, which is one of the most important principles of traditional Chinese medicine (TCM). According to the "Same Treatment for Different Diseases" principle, ANP might be efficacious in other CNS diseases.

Full text

Review Article
Use of Angong Niuhuang in Treating Central Nervous System
Diseases and Related Research
Yu Guo,1,2 Shaohua Yan,1Lipeng Xu,1,2 Gexin Zhu,1Xiaotong Yu,1,2 and Xiaolin Tong1
1Endocrinology Department of Guang An Men Hospital, China Academy of Chinese Medical Science, Beijing 100053, China
2Beijing University of Chinese Medicine, Beijing 100029, China
Correspondence should be addressed to Xiaolin Tong; xiaolintong@sina.com
Received  August ; Revised  October ; Accepted  December ; Published  December 
Academic Editor: Paul Siu-Po Ip
Copyright ©  Yu Guo et al. is is an open access article distributed under the Creative Commons Attribution License, which
permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
In Chinese medicine-based therapeutics, Angong Niuhuang pill (ANP) is one of the three most eective formulas for febrile
diseases, and it is also used to treat other diseases. is paper reviews current knowledge regarding the clinical and pharmacological
eects of ANP for treating dierent central nervous system (CNS) diseases to conrm its validity and ecacy. ese diseases are
like centric fever, coma, stroke, and viral encephalitis. is review reveals that various diseases could be treated using the same
agent, which is one of the most important principles of traditional Chinese medicine (TCM). According to the “Same Treatment
for Dierent Diseases” principle, ANP might be ecacious in other CNS diseases.
1. Introduction
e premier description of Angong Niuhuang pill (ANP) is in
Shang Jiao,VolumeOneoftheTreatise on Dierentiation and
Tre atment o f Epidemic Febrile Diseases,writtenbyWu Jutong
in the Qing Dynasty.
CNS diseases manifest mainly at the neural tube, neural
crest, spinal cord, and brain. Typical clinical manifestations
include high fever, headache, dizziness, unconsciousness,
nausea and vomiting, diculty moving, hemiplegic paralysis,
language disorders, weakness, neck rigidity, and epilepsy. In
ancient times ANP was known as the pill that could rescue
the patient immediately and help revive those who were on
the brink of death. It was named “one of the three treasures,”
and was used to treat high fevers []. Today, ANP has the
potential to provide new breakthroughs for the treatment of
CNS diseases such as stroke, coma, centric fever, and viral
encephalitis, as well as the design of clinical studies of these
diseases.
2. Clinical Applications
2.1. Stroke. Strokes can be categorized as ischemic or hemor-
rhagic. Cerebral hemorrhage is a brain parenchymal nontrau-
matichematomathatisprimarilycausedbyhypertensionand
the subsequent clogging of arteries. It normally causes intrac-
erebral hematoma; however, the blood sometimes penetrates
the brain parenchyma, which results in intraventricular and
subarachnoid hemorrhage. e clinical features of this type
of stroke are dizziness, headache, vomiting, loss of con-
sciousness, hemiplegia, hemidysesthesia, and hemianopsia
[]. On the contrast, hypoxic-ischemic encephalopathy is
caused by circulatory or respiratory diseases, which results in
an insucient oxygen supply to the brain. If the brain arterial
oxygen partial pressure falls below  kPa, a lack of oxygen
diusion will result in collateral damage to the brain [].
However, in the theoretical system of traditional Chinese
medicine, stroke that results from impaired function of the
liver,kidney,heart,spleen,andothervisceraproducesa
series of pathological changes including wind (mainly in
liver), internal heat (liver and heart heat), phlegm (wind
and wet phlegm), qi (deciency,reverse ow,andstagna-
tion), and blood (deciency and stasis). Stroke disturbs qi-
movement and leads to a qi-blood imbalance,whichareall
the results of external wind,emotionalchanges,improper
diet, too much physical and mental labor, or excessive sexual
activities []. She and Gao [] ascribed the basic theory
of ANP to wind-yang excess.eyfoundthatwind phlegm
and phlegm re disturbed the upper body, which aroused
mental confusion. e key steps of treatment can bring down
Hindawi Publishing Corporation
Evidence-Based Complementary and Alternative Medicine
Volume 2014, Article ID 346918, 9 pages
http://dx.doi.org/10.1155/2014/346918

 Evidence-Based Complementary and Alternative Medicine
a fever, detoxifying and resolving turbidity and inducing
resuscitation.
Zhan [] randomized  intraventricular hemorrhage
patients into an observation group and a control (C) group.
In addition to conventional treatment, the observation group
was also given with Xing Nao Jing injections, ANP, and
acupuncture. e results showed that intracerebral pressure,
temperature, and the time to recover consciousness were
signicantly better in the observation group than in the C
group (𝑃 < 0.05). Aer  days of treatment, the nerve
function defect grade and the scores of TCM syndrome were
all lower in the observation group than in the C group (𝑃<
0.01).
Moreover, Zhang and Li [] divided  cerebral hemor-
rhage cases in average into two groups, which were treated
with biomedicine or a combination of biomedicine and
Angong and Qingkailing injections. e results revealed
an increased curative eect and treatment ecacy in the
combination group compared with the biomedicine group
(𝑃 < 0.05). e level of disability and death rate in the
combination group were also lower than in the biomedicine
group (𝑃 < 0.05). ese ndings suggest that combining
TCM and biomedicine is eective for reducing the mortality
rates aer cerebral hemorrhage.
In addition, Xing et al. []randomizedpatientswith
cerebral paralysis into a treatment (T) group, which was given
with Angong dissolved in warm water using a nasogastric
tube as well as regular emergency treatment, and a C group,
which received cytidine diphosphate choline, tranquilizers,
and glucocorticoids plus cooling. T group exhibited a cooled
fever (𝑃 < 0.01), coma (𝑃 < 0.05), and convulsions compared
withCgroup.
Wu et al. [ ] conrmed the benets of combining ANP
with biomedicine to treat damaged nerve function in patients
with acute cerebral infarction. Aer treatment, plasma brain
natriuretic peptide (BNP) and C-reactive protein (CRP)
levelsweredecreasedmoremarkedlyinthecombination
treatment group compared with the C group (𝑃 < 0.05).
ese authors stated that use of ANP to reduce plasma BNP
and CRP levels positively aected the neural function of
patients with acute cerebral infarction.
Research regarding the clinical ecacy and safety of ANP
as an adjuvant treatment for moderate or severe neonatal
hypoxic-ischemic encephalopathy (NHIE) revealed that it
aects NHIE. Specically, it could promote patients recovery
anddecreasetheoccurrenceofcomplications[]. Huang
et al. [] reported the clinical eects of ANP during the
treatment of hypoxic-ischemic encephalopathy. Sixty patients
with hypoxic-ischemic encephalopathy were randomized
into a C group given conventional Western medical treatment
and an observation group that also received ANP. Conscious
recovery time, temperature, the occurrence of seizures, the
outcome of the Glasgow Coma Scale (GCS), and clinical e-
cacy were compared between groups. e observation group
had higher GCS scores (𝑃 < 0.02)thantheCgroup.e
observation group also had more stable body temperatures
andshowedfewerconvulsionscomparedwiththeCgroup.
All comparisons were statistically signicant (𝑃 < 0.05). Xiao
[] randomized  patients with ischemic stroke and a
diagnosis of phlegm-heat syndrome into either a comparison
group, which received Western medical treatment, or an
observation group that was administered the basic Western
treatment as well as ANP (one pill orally twice a day). e
TCM syndrome scores that evaluated routine daily living
activities, assessed changes in neurological function, and
analyzed the standards of clinical ecacy revealed that the
basic characteristics of the two groups were not signicantly
dierent. Following treatment, the TCM syndrome scores
of the observation group regarding neurological function,
daily activities, and overall eciency were %, .%, and
.%, respectively, compared with %, .%, and % in
the comparison group. e results revealed that ANP was
highly eective for curing ischemic stroke and phlegm-heat
syndrome.
2.2. Coma. During a coma the depression of cortical and
subcortical mesh structures and functions results in severely
disturbed consciousness. Patients might become semicon-
scious or unconscious, which is apparently a lack of reaction
to pain stimuli and of voluntary movement. Because of
the suppression of higher nerve activity, various external
stimuli are unable to trigger actions including motor reexes,
swallowing, and reaction to light []. ere are two etiologies
of coma. One results from a primary injury to the cerebral
cortex, diencephalon, midbrain, and the top of the pons,
whereas the other might result from brain injury, secondary
systemic toxicity, metabolic blocks, or an endocrine imbal-
ance [].
2.2.1. Coma Caused by Brain Trauma. Skull damage results in
intracranial hemorrhage, intracranial hematoma, increased
intracranial pressure, ischemia caused by decreased cere-
bral blood ow, hypoxia, cerebral edema, the inammatory
response, and apoptosis, which together give rise to brain
damage and coma. A delay in treating a skull damage-induced
comamightleadtotheformationofacerebralhernia,
which has the highest mortality and disability rate among
all bodily injuries []. Chen and Wang []randomized
comatose traumatic brain injury patients to either treatment
(𝑛 = 133)orcontrol(𝑛 = 1790) groups. Patients in both
groups received the same standard care, but patients in T
group were also given ANP twice daily (g each) for a week.
e outcomes of Glasgow Coma Scale (GCS) and Acute
Physiology and Chronic Health Evaluation II (APACHE II)
showed that T group had signicantly lower level of high-
sensitivity CRP and less severe epilepsy. erefore, it was con-
cluded that ANP had a signicant eect on the treatment of
comatose traumatic brain injury patients. Wang []divided
 comatose traumatic brain injury patients with GCS scores
< into treatment and control groups of  patients. Both
groups received treatment to prevent dehydration, maintain
hemostasis, reduce intracranial pressure, and prevent infec-
tion. Patients in the treatment group were given additional
treatments including ANP and head electroacupuncture
combined with hyperbaric oxygen therapy. Aer  weeks the
T group had a better sober rate (𝑃 < 0.001)andGCSscores
(𝑃 = 0.002) than the control group. Furthermore, the T group
had signicantly lower rates of gastrointestinal bleeding

Evidence-Based Complementary and Alternative Medicine 
(𝑃 = 0.005) and pulmonary infection (𝑃 = 0.015)thanthe
control group, which suggests that the addition of ANP and
head electroacupuncture plus hyperbaric oxygen therapy to
the normal treatment increased the therapeutic eectiveness
anddecreasedtherateofcomplications.
Lin et al. [] treated comatose traumatic brain injury
patients by using naloxone only in the control group and
naloxone together with ANP in the treatment group. ey
reported signicant dierences in sobriety and intense coma
(mortal) rates between the two groups (𝑃 < 0.05). ere
was also a big dierence in GCS between the treatment
(35.6 ± 1.8)andcontrol(19.3 ± 1.2,𝑃 < 0.01)groups.
Data revealed that the combined use of ANP and naloxone
was more eective for the treatment of comatose traumatic
brain injury patients than use of naloxone alone. Wang et
al. [] evaluated the eect of combining ANP with conven-
tional therapy on brain trauma-induced diuse axonal injury.
Compared with the control group that received conventional
therapy alone, the combined therapy improved conscious-
ness disorder, body temperature, and decerebrate tetanus in
patients to yield favorable prognosis. Li et al. []found
that the recovery time and disease course in patients treated
using ANP combined with biomedicine were shorter than
in patients only treated with biomedicine. In a prospective
randomized clinical trial of  craniopathy patients with
unconsciousness, the addition of ANP to routine treatment
signicantly increased the eciency (𝑃 < 0.005)ofprocesses
used to enhance the excitation processes within the cerebral
cortex of unconsciousness patients [].
2.2.2. Coma Caused by Blocked Cerebral Blood Circulation.
Li et al. [] assessed the eects of ANP on severe cerebral
vascular disease in elderly individuals. e research team
divided  patients into a control group that received regular
treatment and the second group that were administered
regular treatment plus ANP. e total rate of eectiveness,
which was dependent on the clinical neural function, was
higherinthetreatmentgroup(.%)thaninthecontrol
group (.%, 𝑃 < 0.05). e GCS scores were increased
signicantly from baseline in both groups (𝑃 < 0.05), but
the score in the treatment group was higher than that in the
control group (𝑃 < 0.05). In addition, the reduced neurolog-
ical decit scores were higher in the treatment group than in
the control group. Statistics revealed that ANP could promote
the recovery of awareness in patients with severe cerebral
vascular diseases. Shi [] evaluated the eect of the com-
bination of TCM and biomedicine in  patients with coma
caused by brainstem hemorrhage, which shows the benets of
combining Chinese and biomedicine are obvious. Zhang and
Qu [] learnt the eect of ANP combined with biomedicine
for treating hypertensive cerebral hemorrhage. e time of
coma in the treatment group (ANP plus biomedicine) was
shorter than that in the control group (biomedicine only; 𝑃<
0.05). Consistent with this, the neural disorder scores were
lower in the treatment group than in the control group (𝑃<
0.05). However, there were no signicant dierences in blood
pressure uctuation or mortality rate between the two groups.
erefore, ANP promoted recovery from coma and improved
patient prognosis. Qiu and Wu [] studied  rst-episode
patients with an altered mental status following acute cerebral
infarction. All patients received conventional treatment, but
 patients were also administered ANP nasally. e GCS
scores of all  patients improved greatly. However, there
were statistically signicant dierences in the improvement
between the therapy and control groups regarding hemat-
ocrit, brinogen, and blood viscosity (𝑃 < 0.01). erefore,
ANP signicantly inhibited platelet aggregation, prevented
blood clots, and lowered blood viscosity to facilitate the
reversal of narcosis.
2.2.3. Infantile Coma. Li treated  children with infantile
coma by using ANP combined with biomedicine []. Aer
the treatment all but two of the children became fully
conscious. ese results suggest that ANP plus biomedicine
has a huge curative eect on infantile coma and that ANP
could counteract adverse reactions to sedative drugs such as
diazepam and phenobarbital sodium.
2.2.4. Coma Caused by Infectious Diseases. Wang and Zhang
[] evaluated the eect of combining ANP with biomedicine
on infectious disease-induced coma. Based on TCM syn-
drome dierentiation, patients in the treatment group were
given dierent decoctions in addition to ANP. Patients in the
treatment group had signicantly higher GCS scores than the
control group (𝑃 < 0.05), which conrms the applicability of
the ANP toward promoting the heat-clearing and detoxifying
functions, brain activity, and regaining consciousness.
2.3. Centric Fever. Centric fever is a nonpyrogenic fever
resulting from centric damage and an increased temperature
inthecentrum.emainclinicalfeatureisaconstantfever
that is caused by the eects of cerebrovascular disease, cranial
trauma,andMalinsyndrome[]. Shi and Tang [] explored
the antipyretic eects of ANP on centric high fever in 
patients with dierent TCM syndromes including qi system
heat excess syndrome inthechannelsandcollaterals(cases)
and heat excess syndrome and fu organ constipation in the
internal organs ( cases). e data revealed that ANP exerted
denite antipyretic eects on a centric high fever because
the % eectiveness rate was observed. Zhang et al. []
randomized  cranial trauma patients into groups that
received ANP combined with biomedicine (CW; 𝑛 = 126)or
biomedicine only (W; 𝑛=80). ANP was administered nasally
by tube or orally depending on the TCM syndrome. e CW
group had a signicantly greater improvement than the W
group (𝑃 < 0.01). In an additional study, Feng []randomly
assigned conrmed centric fever patients into treatment (T;
𝑛=33) and comparison (C; 𝑛=32) groups, and using
basic physical cooling methods treated both groups, and the T
group also received ANP (orally/lavage/enema). e T group
had an eectiveness rate of .%, which was signicantly
higher than the C group (.%; 𝑃 < 0.01). Li and Bao []
assigned  patients with cranial trauma, centric fever, and
similar baseline characteristics into groups that received a
regular Western treatment for centric fever (group C; 𝑛=50)
or Western treatment plus ANP (group T; 𝑛=50). e T
group had a mean cooling time of  h, compared with  h
in the C group. A follow-up survey revealed that the T group

 Evidence-Based Complementary and Alternative Medicine
survivors had a better quality of life. Zhang and Wang []
assessed the eect of ANP in patients with centric fever that
was caused by cerebral hemorrhage. e overall eectiveness
of treating centric fever by using traditional and biomedicine
(treatment group; 𝑛=36) was higher than using biomedicine
alone (control group, 𝑛=36;𝑃 < 0.01). Jiang []combined
ANP via nasal feeding with biomedicine to treat  patients
with fever that was caused by massive cerebral infarction and
treated without mild hypothermia and hibernation therapy.
e results showed that the eective rate of cooling and
recovered consciousness was .%. erefore, ANP is highly
eective at increasing the recovery of consciousness and
cooling body temperature in patients with massive cerebral
infarction and a high fever.
2.4. Viral Encephalitis. Viral encephalitis is an acute intracra-
nial inammation that is caused by a variety of viruses and is
characterized by fever, headache, vomiting, unconsciousness,
or mental abnormalities. In mild cases full recovery is
possible without medical treatment, whereas severe cases can
result in death or complications. Meningitis is caused by
several dierent viruses and has dierent seasonal incidence
and typical clinical features.
In terms of TCM, viral encephalitis is caused by exposure
to exogenous pathogenic heat, including wind heat,summer
heat,anddryness heat.elung and stomach are the foci of
the lesions involving the heart and liver.Duringtherecovery
stage the lesion organs are the spleen,liver,andkidneys.e
disease results from the conversion of exogenous pathogenic
heat into dryness aer the heat-re attack to the human body.
Viral encephalitis is a common acute disease with a high
prevalence and complicated course; the extreme heat causes
wind and re.epathogenicconditionspreadsandchanges
according to the system of the Defense-qi-Nutrient-Blood, as
well as heat,phlegm,andwind [].
Yu [] randomly assigned  children with viral
encephalitis into treatment (T; 𝑛=13)andcomparison
(C; 𝑛=17) groups. Both groups were given conventional
Western treatments such as antiviral agents, treatment for
dehydration, procedures to decrease the intracranial pres-
sure, and anticonvulsants. e T group was also given ANP
via the mouth or nasal feeding. e clinical evaluation and
clinical course were better in the T compared with the C
group (𝑃 < 0.05). A retrospective clinical analysis by Yao et
al. [] was performed on the clinical data of  patients with
viral encephalitis. e recovery rate and CT or MRI images
indicated that the outcome of the group treated with ANP,
acyclovir, mannitol, and adrenocortical hormone was better
than that of the biomedicine group.
Wang a n d D on g [ ] measured cerebrospinal uid NO
and TNF-𝛼levels in three children groups suering from viral
encephalitis, febrile seizures, and ordinary trauma, respec-
tively. e concentrations were higher in the viral encephalitis
group than in the febrile seizures group and ordinary trauma
group, which shows NO and TNF-𝛼participate in inamma-
tion of the CNS. Zhang et al. [] evaluated the treatment of
 children with viral encephalitis using oral or nasal ANP
combined with basic Western treatment. e total rate of
eectiveness was signicantly higher (.%) in the group
11.30%
17.88%
27.94%
42.88%
Stroke
Coma
Centric fever
Viral encephalitis
F : e distribution of severe nerve disease cases treated with
ANP.
given ANP than in the comparison group (.%; 𝑃 < 0.05).
e levels of TNF-𝛼in the cerebrospinal uid, a standard
marker used to assess the eectiveness of treatment, declined
sharply in both groups. erefore, ANP could decrease TNF-
𝛼levels, improve recovery rates, and reduce the treatment
periods. Liang [] reported the clinical eect of combining
Chinese and biomedicinal therapy to treat viral encephalitis
in children. TNF-𝛼levels in the treatment group, which were
treated using ANP plus biomedicine, declined more steeply
than did those in the control group, which were treated
usingonlyWesternmedicine(𝑃 < 0.05). erefore, the
data reveal signicant advantages of combining Chinese and
biomedicine to treat viral encephalitis.
A total of  cases of severe nerve disease that were
treated using ANP were analyzed in the clinical studies
described above. Among these,  coma cases comprised
.% of the total cases, which was the highest percentage
of the conditions. Analysis of the distribution of the severe
nerve disease cases revealed that coma and viral encephalitis
were the most and least prevalent, respectively (Figure ).
3. Pharmacological Studies
3.1. Cerebral Protection
3.1.1. Reducing Brain Edema. Cephaledema oen follows
intracerebral hemorrhage. Its causes are complex and lead
to pathological changes in physiology and function such as
the formation of intracerebral hematomas, decreased cerebral
blood ow, ischemic anoxia of brain tissue, and metabolic
disorders []. Matrix metalloproteinases, particularly matrix
metalloproteinase- (MMP-), are closely related to the
formation of cephaledema and destruction of the blood-
brain barrier because they can degrade all components of

Evidence-Based Complementary and Alternative Medicine 
the extracellular matrix []. Jiang et al. []foundthat
changes in serum MMP- levels were correlated with the
evolution and volume of brain edema, and that they had a
direct eect on the condition. ANP can reduce brain edema
aer cerebral hemorrhage by regulating the expression of
MMP-.Yinetal.[,] performed two animal experiments
to demonstrate that ANP can modulate the expression of
MMP- and eectively reduce brain edema in rats with
experimental cerebral hemorrhage. Zhu []usedtheFeeney
assayinaratmodelofclosedbraininjurytodemonstrate
that the administration of ANP resulted in a greater decrease
in brain water content and cerebral cortex Evans Blue dye
content compared with the model control and Nimotop
treatment groups. In the ANP-added group, an increase in
synaptic density in the lateral ventricle was observable using
electron microscopy. erefore, ANP could reduce brain
edema by decreasing capillary permeability and improving
the tolerance to ischemia or hypoxia, thereby protecting the
organization of the brain. In a rat model of middle cerebral
arterial occlusion, Zhao [] found that ANP, both with
and without the coadministration of cinnabar and realgar,
could dramatically reduce the cerebral infarction area and
brain water content, increase the levels of catalase (CAT) and
glutathione peroxidase (GPX), and lower the levels of lipid
peroxide (LPO) and lactic acid (LD). is suggests that ANP
couldprotecttheanimalsfromcerebralischemiainawaythat
might be related to its antioxidant eects.
3.1.2. Anti-Inammatory Eects. Yin []developedarat
intracerebral hemorrhage (ICH) model by injecting anti-
coagulated arterial blood into the caudate nucleus. e
inammatory cells around the hematomas were then counted
using H&E staining. In addition, RT-PCR was used to assess
the expression of TNF-𝛼mRNA, and an ELISA was used
to measure TNF-𝛼protein. ANP reduced the number of
inammatory cells around the hematomas, inhibited the
expression of TNF-𝛼mRNA and protein, and inhibited the
inammatory reaction in rats with ICH.
3.1.3. Neuroprotective Eects. Zhang et al. []usedprimary
rat midbrain neuronal-glia cultures as an in vitro model
to measure the neuroprotective eects of dierent agents.
Compared with the normal control group, the number of
dopamine (DA) neurons in the lipopolysaccharide (LPS)
model group was decreased by % (𝑃 < 0.05). LPS also
activated the microglia. e expression of TNF-𝛼and iNOS
mRNA was increased in the microglia in LPS control group
(𝑃 < 0.05). Compared with the LPS control group, LPS-
mediated DA neuronal loss was attenuated signicantly by
% and % by the administration of ANP and realgar,
respectively (𝑃 < 0.05), whereas the activation of microglia
and the expression of TNF-𝛼mRNA were decreased by
% and % (𝑃 < 0.05). ese results demonstrate that
ANP protects against LPS-induced neurotoxicity via anti-
inammatory properties and suggest that realgar might play
a key role in the neuroprotective eects of ANP. In contrast,
cinnabar did not exert any neuroprotective eects. Li et al.
[] studied heat shock protein  (HSP) expression in
rats with cerebral ischemia injury. e infarct volume was
signicantly smaller in the ANP group compared with that
in the ischemia group (𝑃 < 0.05). HSP expression was
signicantly higher in the ANP group than in the ischemia
group. ANP increased HSP expression and protected brain
cells from cerebral ischemia beginning on day .
Zhong et al. [] found that ANP could promote angio-
genesis in the cerebral cortex and striatum of ischemic rats
andalsoincreasetheamountofbloodvesselsintheinjured
area. It also increased neurogenesis in the subgranular zone
(SGZ), subventricular zone (SVZ), cortex, and striatum.
Experimental results assessing the protective eects of ANP
in a model of experimental cerebral ischemia in rats showed
that it could not only decrease the cerebral water content,
but also increase the serum levels of interleukin- (IL-)
[]. is inhibits the expression of the inammatory cell
factors IL-, IL-, and IL- and their receptors, thereby reduc-
ing inammatory reactions and tissue injury []. During
cerebral ischemia and cerebral infarction, IL- facilitates
recovery and the survival of injured neurons by alleviating
inammation and inhibiting neuronal apoptosis in areas of
cerebral hemorrhage [,]. A recent review discussed the
role of ANP in inhibiting nerve cell apoptosis by upregulating
the phosphorylation of Akt, which is the key molecule for the
survival of motor neurons following cerebral ischemia [].
3.1.4. Eects on Nitric Oxide (NO) and Nitric Oxide Synthase
(NOS). NOS participates in the release of free oxygen rad-
icals during brain ischemia-reperfusion. eNOS in vascular
endothelial cells catalyzes the release of NO via L-arginine.
In turn, NO maintains normal vascular function []. Xing
and Zhang [] randomized  patients with cerebral hemor-
rhageintogroupsthatreceivedcytidinediphosphatecholine
(observation group; 𝑛=33) or ANP (comparison group,
𝑛=35
). One week later serum asymmetric dimethylarginine
(ADMA) levels were reduced signicantly in the observation
group compared with those in the comparison group (𝑃<
0.01). However, there was a signicant increase in NO in
the serum of the observation group (𝑃 < 0.01). Liu et
al. [] used a hypertensive (hypervolemic) rat model to
demonstrate that the serum NO content was lower in animals
treated using integrated Chinese and biomedicine compared
with the other three groups (TCM group, biomedicine group,
and control group) (𝑃 < 0.05). Data revealed that ANP
combined with biomedicine could alleviate acute brain tissue
injury during the acute stage of spontaneous hypertensive
cerebral hemorrhage in rats. Yang et al. []veriedthe
protective eects of ANP in acute cerebral hemorrhage by
demonstrating that it could decrease NO levels, NOS activity,
and the cerebral monoamine neurotransmitter content.
3.2. Resuscitation and Sedation Eects. When studying the
sedative eects of ANP and its simplied prescription, Ye et al.
[] found that the administration of ., ., and .g kg−1
ANP once daily with  mg kg−1 pentobarbital sodium
(below the hypnotic threshold) had more pronounced
synergisticsedationeectsthandidthemodelcontrolgroup
(𝑃 < 0.005).

 Evidence-Based Complementary and Alternative Medicine
T : Main pharmacological ingredients and the pharmacological eects of the main constituent herbs.
Herbs [] Main pharmacological ingredients [] Pharmacological eects []
Bezoar
Bilirubin
Bile acid
Deoxycholic acid
Taurine
Cholesterol
Sedation
Anticonvulsion
Antipyretic
Anti-inammatory
Antiviral
Cardiotonic
Antiplatelet
Aggregation
Rhinoceros horn
Keratin
Cholesterol
Calcium phosphate
Calcium carbonate
Sedation
Anticonvulsion
Antipyretic
Anti-inammatory
Antiviral
Cardiotonic
Antiplatelet
Aggregation
Radix scutellariae
Baicalin
Baicalein
Wogonoside
Wogonin
Neobaicalein
Anti-pathogeny microorganism
Anti-inammatory
Antiallergy
Antipyretic
Sedation
Hepatoprotective
Cholagogue
Coptidis rhizome Berberine
Anti-pathogeny microorganism
Antipyretic
Anti-inammatory
Antiallergy
Cholagogue
Sedation
Hepatoprotective
Cape jasmine
Gardenoside
Geniposide
Genipin
Anti-pathogeny microorganism
Anti-inammatory
Anti-allergy
Antipyretic
Sedation
Hepatoprotective
Cholagogue
Musk Muscone
Double-acting role in regulating the CNS,
anti-inammatory
Antiplatelet aggregation
Cardiotonic
Borneol Borneol
Double-acting role in regulating the CNS,
anti-inammatory
Postoperative analgesia
Antimicrobial
Antimyocardial ischemia
Antifertility
Curcuma
Curcumene
Curcumine
Turm e r o n e
Ar-turmerone
Anticancer
Hepatoprotective
Cholagogue
Exciting gastrointestinal smooth muscle
Immunosuppressive
3.3. Antipyretic Eects. Experiments performed by Ye con-
rmed that ANP and its simplied prescription (without
Zhusha and Xionghuang) exerted clear antipyretic and seda-
tive eects in models including rabbits with high fevers
caused by typhoid vaccine, sleeping rats caused by pento-
barbital sodium, oxygen-decient rats killed using NaNO2,
and rats with eclampsia was caused by strychnine nitrate
and PTZ []. Jin and Pan [] administered . g/kg

Evidence-Based Complementary and Alternative Medicine 
ANP by intraperitoneal injection to rabbits, and the rise
in body temperature of the rabbits caused by the triple
vaccine was clearly lower than the control group aer
.–. h.
With the development of pharmacological research, the
main drugs in Angong Niuhuang prescriptions and their
pharmacological eects have been identied, which revealed
that Angong Niuhuang is eective for the treatment of
diseases of the nervous system (Tab l e  ).
4. STDDP Applied in CNS Diseases
RegardlessofthecauseandpathogenesisofthefourCNSdis-
eases described above, their symptoms overlap. For example,
stroke patients and children with viral encephalitis can also be
in a coma or have a high fever. erefore, Chinese clinicians
consider these dierent diseases from a TCM perspective
and nd the common features that represent the same TCM
pathogenesis and then make a decision to use the same
medicine or treatment according to the “Same Treatment
for Dierent Diseases” principle (STDDP), which is a crucial
principle of TCM.
STDDP has been widely applied in TCM. In addition
to the diseases described above, ANP can also be used to
treat pulmonary cerebral disease, insolation, and eclampsia,
which can have common symptoms such as coma and high
fever [–]. As a result, the use of ANP for centuries has
suggested that it could be used to treat CNS diseases by both
Chinese and Western clinicians.
5. Conclusion
Although the mechanism by which ANP cures these dis-
easesandtheactiveingredientswithinANPareyettobe
elucidated, Chinese clinicians have used ANP to treat CNS
diseases for hundreds of years, which suggested that ANP is
both eective and safe.
We realize that clinical research is not an end but a way to
solve clinical problems. With the development of evidence-
based medicine, clinical research has developed from the
case level to the population level, and best evidence has
become the main principle of prescriptions. Findings have
been reported and scrutinized, and TCM research should
continue to be performed in real-world studies to ensure the
reliability of the results.
e results of the literature are persuasive; however, there
are some problems with the way the clinical conditions have
been analyzed. () e clinical observations and research
areofpoorquality.Forexample,mostofthestudieson
stroke patients, including cases of cerebral hemorrhage and
cerebral ischemia, do not report the symptoms fully. Even the
“blockage syndrome”and“prostration syndrome”deviatefrom
the principle of combining disease, syndrome, and symptom.
is could be attributable to a lack of response to treatment.
() Few trials have studied the mechanism of central heat-
ing, which could be attributed to a lack of mature animal
models. () ere is small number of single case reports,
which is consistent with the development of evidence-based
medicine.
Research Highlights
() Because of its fever-reducing, detoxication, and
decongestive actions, ANP has long been used to treat
conditions such as coma, fever, and cephaledema in
China.
() Modern pharmacological studies reveal that ANP
aects the central nervous system by relieving cere-
bral edema, exerting antipyretic and anti-inamma-
tory eects, and allowing resuscitation and sedation,
as well as other related actions.
() e indication for ANP in treating CNS diseases
highlights the “Same Treatment for Dierent Diseases”
principle.
Disclosure
e paper is original, has not been submitted to and is not
under consideration by another publication, has not been
previously published in any other language or form, including
electronic version, and contains no disclosure of condential
information or authorship/patent application/funding source
disputations.
Conflict of Interests
e authors declare no conict of interests.
Authors’ Contribution
Yu Guo and Shaohua Yan collected data and wrote the paper.
LipengXu,GexinZhu,andXiaotongYuprovideddataforthe
paper. Xiaolin Tong reviewed the paper. All authors approved
the nal version of the paper.
Acknowledgment
is work is supported by the National Basic Research
Program  (no. CB).
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