Development of a novel phytopharmaceutical medicine derived from Traditional Chinese Medicine for the treatment of Parkinson's disease.

Abstract

Introduction:
Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the third most common cause of death in industrialized countries. Given the lack of neuroprotective conventional medicines, investigation of Chinese Medicine herbs (CMH) holds a high potential for the development of novel therapeutic concepts.

Materials and Methods:
We established a hypothesis driven screening approach to identify potentially neuroprotective CMH [1]. The initial screening of watery extracts for their neuroprotective effect against oxidative stress induced cellular damages revealed that Coptis chinensis (CC) was the most promising herb.

Results:
Further analysis showed that pre-treatment of neuroblastoma cells with CC or Coptisine has three effects: attenuation of oxidative stress-induced decrease in cell viability, protection of the mitochondrial membrane potential, and reduction of apoptosis. PD related investigations revealed that CC, Coptisine and Berberine protect neuroblastoma cells and mice from MPP+/MPTP induced toxicity, respectively, in a dose dependent manner. These findings suggest that neuroprotective effects of CC might be caused by an improvement of mitochondrial function, stabilization of intracellular ATP concentration, attenuation of mitochondrial permeability transition, reduction of cytochrome C release and prevention of apoptosis.

Conclusions:
These results can be seen as a promising starting point for the development of new treatment concepts for PD and other neurodegenerative diseases. However, multi-factorial diseases like PD require a multi-target approach for affecting different dysregulated pathways. Hence, we aim to combine several herbs (or compounds) which act via different pathways to achieve additive or synergistic effects for an increasement of the therapeutic efficacy.

Full text

World J Tradit Chin Med 2016; 2(2)
www.wjtcm.org 2016 Vol. 2 Issue 2
75
Oral Presentations
O-01
A NEW METHOD FOR QUANTITATIVE THE
GLYCOPROTEIN IN BIOLOGICAL SAMPLES
Yang Gao, Hongyue Li, Duoduo Xu, Mingxing Wang,
Qipin Gao
Changchun University of Chinese Medicine, Key
Laboratory of effective components of TCM, Ministry of
Education, China. Changchun, 130117 China
Jilin Key Laboratory of Macromolecules in Chinese Drug.
Changchun, 130117 China
Correspondence: Qipin Gao, e-mail: gaoqipin@sina.com
Objective: To set up a new method to detect the sugar
complex in biological samples. Methods: The
glycoprotein purified from the mycelium extract of
Tremella fuciformis was marked with iodine through the
iodine substitution reaction and the content of iodine,
which is representative the amount of the marked trmella
glycoprotein (ITG), was detected with ICP-MS. The
methodology was performed and found the method is
stable, sensitive, and accurate at the detecting the content
of iodine substituted glycoprotein by ICP-MS. The
method was used in the quantitative analysis of biological
samples about their content of ITG, including blood and
organs. Different biological samples were collected from
rats after administration ITG orally and were tested their
iodine contents by ICP-MS to calculating the amount of
ITG in the samples. Result: The results suggested that
the iodine glycoprotein in blood or organs is able to be
detected by ICP-MS with sensitive, stable and accurate
characters. Conclusion: Glycoprotein is easy to be labeled
with iodine to form stable derivative in animal body and
the iodine derivative of glycoprotein can be detected with
ICP-M. The methodology studies reveal the method is
sensitive, stable and easy to perform, which could be used
wildly in the study on glycoprotein, speciously in its
pharmacokinetic.
O-02
TRADITIONAL MEDICINE, NATURAL PRODUCTS,
MMPS AND THE MOLECULAR BASIS OF
THERAPEUTICS
Bipin G. Nair
Amrita School of Biotechnology, Amrita Vishwa
Vidyapeetham, Amrita University, Kollam, Kerala 690525,
India
Correspondence: Bipin Nair, e-mail:
bipinnair03@gmail.com
Objective: To decipher the molecular mechanisms
involved in the regulation of MMP-2 and MMP-9 by
anacardic acid, isolated from cashew nut shell liquid and
a natural product-like flavonoid analog, (I-3,
II-3)-biacacetin and implications for cancer therapy.
Methods: Anacardic acid from cashew shells and (I-3,
II-3)-biacacetin synthesized through oxidative
dimerization of poly-substituted diaryl-1,3-diketones
with cerium ammonium nitrate followed by double
cyclodehydration were characterized using IR, UV, HPLC,
Mass Spectrometry and NMR. Human fibrosarcoma cells
were treated with the compounds and the effect on
gelatinase activity was studied using gelatin zymography,
gelatin degradation and a fluorescence-based assay. qPCR
analysis and Western blotting was used for expression
studies. Results: Anacardic acid and (I-3, II-3)-biacacetin
inhibits MMP-2 and MMP-9 gelatinolytic activity (1, 2).
Furthermore, fluorescence-based studies with catalytic
domain revealed that anacardic acid inhibits MMP-2
catalytic activity in a dose-dependent manner. The
carboxylate group, hydroxyl group binds and the
lipophilic C15 of anacardic acid were found to be essential
for the inhibitory activity. Unlike the zinc dependent
inhibition of gelatinases by anacardic acid, the inhibition
by biacacetin is independent of zinc. Further, a
combination of anacardic acid with biacacetin at
concentrations that are 10 fold lower than that of either
compound alone, resulted in significant enhancement of
inhibitory activity. Conclusions: Anacardic acid and (I-3,
II-3)-biacacetin act as potent inhibitors of gelatinase
activity which in turn gives a strong impetus for the
natural products drug discovery paradigm by providing
a new template for MMP-2/MMP-9 drug discovery.
O-03
DEVELOPMENT OF A NOVEL
PHYTOPHARMACEUTICAL MEDICINE DERIVED
FROM TRADITIONAL CHINESE MEDICINE FOR
THE TREATMENT OF PARKINSON'S DISEASE
Friedemann T a, Li M b, Fei Jc, Ying Y c, Wang WG c, Song
Jb, Kramer ER d, Schumacher U e, Leung AKM b,
Schroeder S a
aHanseMerkur Center for Traditional Chinese Medicine
at the University Medical Center Eppendorf, Hamburg
bHong Kong Baptist-University, Hong Kong
cTongji University, Shanghai
dCentre for Molecular Neurobiology Hamburg (ZMNH),
Hamburg
eUniversity Medical Center Hamburg-Eppendorf,
Department of Anatomy 2, Hamburg
Correspondence: Sven Schroeder, e-mail:
Schroeder@tcm-am-uke.de
Introduction: Alzheimer’s disease (AD) and Parkinson’s
disease (PD) are the third most common cause of death in
industrialized countries. Given the lack of
neuroprotective conventional medicines, investigation of
Chinese Medicine herbs (CMH) holds a high potential for
the development of novel therapeutic concepts. Materials
and Methods: We established a hypothesis driven
screening approach to identify potentially
neuroprotective CMH [1]. The initial screening of watery
extracts for their neuroprotective effect against oxidative
stress induced cellular damages revealed that Coptis
chinensis (CC) was the most promising herb. Results:
Further analysis showed that pre-treatment of
neuroblastoma cells with CC or Coptisine has three

World J Tradit Chin Med 2016; 2(2)
www.wjtcm.org 2016 Vol. 2 Issue 2
76
effects: attenuation of oxidative stress-induced decrease in
cell viability, protection of the mitochondrial membrane
potential, and reduction of apoptosis. PD related
investigations revealed that CC, Coptisine and Berberine
protect neuroblastoma cells and mice from MPP+/MPTP
induced toxicity, respectively, in a dose dependent
manner. These findings suggest that neuroprotective
effects of CC might be caused by an improvement of
mitochondrial function, stabilization of intracellular ATP
concentration, attenuation of mitochondrial permeability
transition, reduction of cytochrome C release and
prevention of apoptosis. Conclusions: These results can
be seen as a promising starting point for the development
of new treatment concepts for PD and other
neurodegenerative diseases. However, multi-factorial
diseases like PD require a multi-target approach for
affecting different dysregulated pathways. Hence, we aim
to combine several herbs (or compounds) which act via
different pathways to achieve additive or synergistic
effects for an increasement of the therapeutic efficacy.
O-04
INDIRECT GENOTOXICITY OF HERBAL
MEDICINES
Amandine Nachtergael, Mélanie Poivre, Pierre Duez
Unit of Therapeutic Chemistry and Pharmacognosy,
Faculty of Medicine and Pharmacy, Research Institute for
Health Sciences and Technology, University of Mons
(UMONS), 20 Place du Parc, 7000 Mons (Belgium)
Correspondence: Pierre Duez, e-mail:
pierre.duez@umons.ac.be
Herbal medicines are widely used worldwide, either as
primary health care or complementary medicines. The
toxicology of most herbs has however not been
thoroughly investigated and their safety is generally
assumed from long-standing use. For mid- to long-term
toxicities, such as genotoxicity, that are generally not
detected through traditional use, the situation is more
complex and requires more scientific evidence for their
putative harmlessness. To this end, a plethora of methods
[1] exist, more or less satisfying; structural alerts, in silico
and classical in vitro and in vivo predictive methods are
often used on a herb-by-herb basis. These tools are still a
cornerstone for toxicological evaluation but appear
ill-suited to study multicomponent and variable herbal
mixtures [2]. The European Committee on Herbal
Medicinal Products (HMPC) has proposed a genotoxicity
testing guideline based on the Ames test; this strategy is
however heavily debated as some ubiquitous compounds,
Ames-positive but not genotoxic to eukaryotes, could
mask hazardous genotoxins.
Also many factors can compromise the safety of herbal
treatments, ranging from intrinsic factors of quality to
external contaminations or various
pharmacological/pharmacokinetic interactions. Of note,
we recently provided evidence for indirect genotoxicity,
i.e. induction or potentiation of a herb genotoxicity by a
co-administered herb (Aristolochia-Magnolia) [3]. Given the
various mechanisms for genome maintenance, the
possibilities of such interactions are not negligible and
should be considered in developing further guidelines to
test the actual preparations/mixtures delivered to
patients.
O-05
ON A NOMENCLATURE APPROPRIATE TO
ORIENTATION FOR CHINESE MEDICINES
Bo-Ying Ma, Alicia Grant
Xinglin Postgraduate College of TCM
Correspondence: Bo-Ying Ma, e-mail:
collegexpct@yahoo.co.uk
Chinese medicine is a great treasure house, which
safeguarded and has continually been safeguarding the
health and well-being, prevention and treatment of
diseases of people in China and worldwide. When
western medicine transferred into China ca. 200 years ago,
there were not many arguments on the orientation of
Chinese medicine but during the recent 20 years this
question has arisen and it is creating many obscurities
and puzzles for western people since Chinese medicine
became popular and widely used. What is an appropriate
nomenclature to the orientation of Chinese medicines? In
the west, for the taking or oral ingestion there are only
two categories: FOOD or MEDICINES in which the
orientation of Chinese medicines was omitted. In the
tradition of Chinese culture medicines and food come
from the same source and they could be used for both
food and medicine according to their purpose and who
gave them. However, western administrative
management does not agree to mix up sale and use in the
market. There are two different systems of medicine in
the world: western medicine and Chinese medicine that,
in this case, cannot get along with each other. Chinese
medicines cannot accept the standard of western
medicine because they do not belong to the western scope
of medicine. The orientation of Chinese medicines should
be placed between food and medicines in the western
categories. We believe that this objective fact should now
be acknowledged and respected. This paper would give
reasonable evidence from history, traditional theory and
clinical practice of Chinese medicine for the suggestion.
O-07
COMPARISON OF ENRICH-BLOOD BIOACTIVITY
AMONG VARIOUS SPECIES AND GRADE OF
DANGGUI HERBS
Bowen Yang a, Xi Li b, Xiaoxiao Wang c, Qinwen Yang a,
Zuyuan Rong b, Lihong Zhang b, Shuang He b, Hongping
Wei b, Guanghua Lu a
aSchool of Pharmacy, Chengdu University of Traditional
Chinese Medicine, Chengdu 611137, China;
bSichuan Institute for Food and Drug Control, Chengdu
611730, China
cDeyang Institute for Food and Drug Control, Deyang
618000, China;
Correspondence: Guanghua Lu, e-mail: