Why mechanism of herbs?

1

Lecture 8 Drug Target Identification and
Mechanistic Study of HerbsY.Z ChenDept. of
Comptational ScienceNational University of
Singapore

• Why mechanism of herbs?
• Why computer approach?
• How it works?
• Performance Analysis and future plan

2
Herbal Medicine and Society

• Widely used in Asian (China, India, Japan, Korea,
  Singapore etc. ) and other nations (120 nations
  established relevant organizations and
  facilities, as reported by XinHua news agency in
  24/2/2000).
• Increased popularity in western countries (12 of
  the population in USA used herbal medicine in
  1997, as reported in Journal of American Medical
  Association).
• Important sources for new drug discovery (1/3 of
  top selling drugs in the market derived from
  herbal ingredients, as reported in Drug Discovery
  Today).
• Increased RD investment in North America,
  Europe, Japan, China, Taiwan, and Hong Kong.
  Singapore established a TCM taskforce since 2000.

3
How Western Drugs Work?
Drug Therapeutic Target (Disease
related protein) gt Beneficial effect
Toxicity and side-effect inducing
proteins gt Adverse effects One drug, single
therapeutic target Drug optimized with the best
therapeutic effect
4
How Herbal Products Work?
Synergy of Multiple Herbal Ingredients Aganist
Multiple Targets

• Mixture of multiple herbs
• Actions gt Simple sum
• Synergy
• Mutual enhancement
• Mutual counteraction
• Maintenance and balance
• Multiple targets
• Therapeutics
• Symptom treatment
• Toxicity/side effect modulation
• Drug delivery and clearance
• Boost of immune system
• Energy, PH, temperature balance/restoration
• Harmonization

Pharmacology Therapeutics 2000, 86191-198
5
Why Mechanism of Herbal Products?

• Current and future work necessary to advance
  herbal medicines
• Standardization in herbal composition
• Analytic chemistry
• Scientific proof and optimization
• Need info about the related targets
• Discovery of novel cocktail approaches
• Need understanding of how herbal ingredients work
  in synergy.

6
Why Computer Approach?

• Existing experimental methods costly and
  time-consuming.
• Limited resources
• Limited availability of herbs
• Difficulty in chemical synthesis and bioassay.
• Feasibility of computer approach
• Information availability
• herbal ingredients, disease and toxicity related
  proteins.
• Software technology
• INVDOCK and machine learning.
• Computer capacity
• Higher speed and lower cost

7
How It Works?
 
Computer Match-Making
Therapeutic Target
Therapeutic Target Database ?
Herbal Ingredient
Herbal Formula Database ?
Computer Match-Making Software ?
Toxicity Target
ADME protein
Drug Adverse Reaction Target Database ?
Matched Pairs
Herbal Ingredient Database ?
Drug Absorption Distribution Metabolism Excretion
Database ?
Mutual Enhancement ? Mutual Counteraction
? Maintenance or Balance ? Delivery or Clearance ?

• Collective therapeutic and maintenance effects
• Toxicity / side effects and modulation
• Drug delivery and clearance

Y.Z. Chen and D.G. Zhi Proteins 200143 217
8
Gingko as An Example Ingredients in Its Leaf
Extract
9
Gingko as an Example Query Results from HICD
10
Gingko as an Example Query Results from HICD

Selection criterion
11
Gingko as an Example Query Results from
Database Search

12
Structure of Important Active Ingredients in
Gingko Leaf Extract

13
Identified Therapeutic Targets of Quercetin
Y. Z. Chen, etc. American Journal of Chinese
Medicine, 30, 139-154. (2002).
14
Predicted and Observed Therapeutic Effects of
GingKo
15
Comparison Between Prediction and Experiments