Transcript PowerPoint **

Modernization of Traditional
Chinese Medicines –
possible synergies between
TCM and western medicine
Clara Bik-San Lau
Associate Director
Institute of Chinese Medicine and State Key Laboratory of
Phytochemistry and Plant Resources in West China
The Chinese University of Hong Kong
Academic Roundtable organized under the auspices of the Czech Ministry of health
23 February 2017
Research Design
Efficacy Driven, Three Prong Approach
Clinical Trial Leading, Biological Tests & Quality Control in Parallel
Biological Tests
Mechanisms
of Action
Difficult
Clinical
Problem
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Possible
solution
with
Chinese
Medicine
Literature
review
Expert
opinion
Herbal
Preparation
(GMP)
Allergic conditions
Viral infection
Degeneration
Derangement
Chronic problems
Cancer
Prevention
Quality Control
and Safety
 Cell line culture
 Bioassays with
animal model
Evidence-based
clinical trials in
compliance with Good
Clinical Practice
(GCP)
 Toxicity screening
 Authentication
(chemical & DNA
fingerprinting)
 Stability, long term
safety
 Quality
refinement
 Optimization
of formula
 Pharmacokinetics
 Pharmacodynamics
 Drug/Product
development
Modernization of Traditional
Chinese Medicines
A Twin Herb Formula
Salviae Miltiorrhizae Radix
(Danshen)
Puerariae Lobatae Radix
(Gegen)
Best known herb in
Chinese medicine
for improving circulation
A soup ingredient for
clearing heat and
high blood pressure
DG decoction
1.
2.
3.
4.
5.
6.
7.
Danshensu
Protocatechuic aldehyde
Puerarin
Daidzein 8-C-apiosyl-glucoside
Daidzin
Salvianolic acid B
Daidzein
DG - A Modern Cardiovascular Tonic
Target: Maintenance of cardiovascular health through protection of
vascular flow via control of intimal thickness
Trials
Patients characteristics
Major findings
1
Patients with coronary
occlusion
Carotid intima-media thickness was improved after DG
treatment
2
Patients with
hypertension
Endothelium-dependent flow-mediated dilation and
carotid intima media thickness improved significantly
during DG treatment
3
Postmenopausal women
with rising cholesterol
DG improved the carotid intima thickness, lowered LDL
and total cholesterol.
4
Patients with peripheral
vascular disease
(Ongoing)
Pre-clinical experiments verified the anti-atherosclerosis,
anti-hypertension and anti-stroke activities of DG
Tam et al. (2009). The Journal of Alternative and Complementary Medicine 15(4):415–421.
Lam et al. (2010). Journal of Ethnopharmacology 132:186-192.
Koon et al. (2011). Journal of Ethnopharmacology 138:175-183.
Woo et al. (2013). Evidence-Based Complementary and Alternative Medicine 2013:132912.
Kwok et al. (2014). Complementary Therapies in Medicine 22(3):473-480.
Beneficial herb-drug interaction
synergies between Chinese and Western medicines
Chemotherapy
Chinese
herbal
medicines
Adjuvant therapy
 Enhance efficacy
 Alleviate sideeffects
Radiotherapy
Lau CBS, Yue GGL, Fung KP, Tan NH, Leung PC. (2015). Science 347, no. 6219, S45-S47.
Modes of action:
• Cytotoxicity
• Immunomodulation
• Anti-angiogenesis
• Anti-metastasis
Study 1: Colorectal cancer chemotherapy
First-line chemotherapeutics:
FOL– Folinic acid (leucovorin)
F – Fluorouracil (5-FU)
OX – Oxaliplatin (Eloxatin)
(Avastin)—a recombinant humanized
monoclonal antibody that blocks
angiogenesis by inhibiting vascular
endothelial growth factor
Curcumin
Bevacizumab
Turmeric extract
Human colon
tumor-bearing mouse
Yue et al. (2010). Food and Chemical Toxicology 48(8-9):2011-20.
Yue et al. (2010). International Journal of Biological Macromolecules 47(3):342-347.
Yue et al. (2015). Journal of Functional Foods 15:243-53.
Inhibitory effects on tumor growth:
Turmeric
extract
+ Avastin possessed
FOLFOX + Avastin
extract
with
Avastin
potent
 Combination of turmeric
Effects on weight
loss:effects
anti-tumor effects without observable
side
Turmeric extract + Avastin << FOLFOX + Avastin
 Adjuvant use of turmeric extract in colorectal cancer therapy
• Turmeric extract and Avastin treatment
significantly extended survival of tumorbearing mice.
• No observable side effect induced by
turmeric extract treatment while significant
side effects were found in FOLFOX-treated
mice.
Study 2: Metastatic breast cancer chemotherapy
X
Conventional
dose
Anti-resorptive treatments
reduce bone destruction in
patients with breast cancerinduced bone metastases
Metronomic
dose
(0.0125 mg/kg twice
a week for 4 weeks)
More metastasis
Hypothesis of preclinical studies
Herbal medicines (e.g. Coriolus versicolor)
could synergistically enhance the action of
metronomic zoledronate in inhibiting the
breast cancer cells growth and metastasis.
Luo et al. (2013) Cancer Letters 339:42-48.
Less bone protection
Coriolus versicolor
Intratibial breast cancer-induced osteolysis mouse model
Zoledronate (ZOL)
Coriolus versicolor (CV)
 Combination of Coriolus versicolor could enhance the action
of metronomic zoledronate in inhibiting the breast cancer cells
growth and metastasis
 Adjuvant use of the herbal extract in metastatic breast cancer
therapy
Inhibitory effects on
 tumor growth: ZOL + CV >> ZOL alone
 metastasis to lungs and livers: ZOL + CV > ZOL alone
 decrease in bone volume: ZOL + CV > ZOL alone
Ko CH, et al. (2014). European Journal of Integrative Medicine 6:730.
Ko CH, et al. Submitted to Journal of Ethnopharmacology (under review)
Study 3: Esophageal cancer chemotherapy
Aqueous extract of Andrographis paniculata (APW)
enhanced
anti-migratory
activities
of
chemotherapeutics cisplatin plus 5-fluorouracil in
esophageal cancer cells
APW
Mice bearing intraperitoneal
human esophageal tumors
cisplatin +
5-fluorouracil
Intraperitoneal xenograft-bearing mouse model
 APW + high-dose chemotherapeutics
 tumor weights
 APW alone or chemotherapeutics or
in combination  tumor nodules
numbers
Combination of Andrographis paniculata extract with cisplatin
and 5-FU:
enhance anti-tumor efficacies of chemotherapeutics
 Additive effect between APW
reduce cancer metastasis
and high dose chemotherapeutics
on tumor inhibition
reduce side effects of chemotherapeutics
 Survival could be prolonged by
Adjuvant value of Andrographis
paniculata
extract in
high-dose
chemotherapeutics
and combined treatments
metastatic esophageal canceralone
management
 Combined treatments  the
elevated LDH and CK levels
Li L, et al. Submitted to Scientific Reports (under revision)
The role of Chinese herbal medicines
Drug
development
Chinese
herbal
medicines
Active
compounds
Extracts/
active
fractions
Health
supplements
development
Adjuvant
therapy
International collaborators
Prof. Keith Harding
Prof. Wen Jiang
Prof. Ingrid Herr
Prof. Han-Dong Sun
Prof. Ning-Hua Tan
Prof. Ming-Hua Qiu
Prof. Jian-Xin Pu
Prof. Xiao-Dong Luo
Prof. Wei-Lie Xiao
Prof. Hiromichi Itoh
Prof. Claude Jolivalt
Prof. Valerie Schini-Kerth
Prof. Edward Kennelly
Dr. Barrie Cassileth
Dr. Gary Deng
Prof. Daniel Sze
Prof. Simon Poon
Prof. Andreas Evdokiou