WP3 – Toxicology of CHM

WP3 overview

WP3 is led by Prof. Duez Pierre of Université Libre de Bruxelles (ULB), Belgium and Prof. Xinmin Liu of IMPLAD, China. The assessment of the safety and efficacy of Traditional Chinese Herbal Medicines (CHMs), are more complex than those for conventional medicines. Indeed, Traditional Chinese Medicine (TCM) presents a unique set of pharmaceutical theories that include particular methods for processing, combining and decocting CHM, which probably contribute to reduce their eventual toxicity and enhance their efficacy. The evaluation of CHM safety is complicated by multiple factors, such as the geographical origin of plant material, different processing techniques, dosage, route of administration and compatibility with other medicines. WP3 aims to review the application of safety evaluation methods to CHM that combine newly evolved and rapidly developing techniques, especially functional genomics, with essential animal, cell culture and molecular biology experiments. WP3 has defined the meaning of “toxicity” with regard to its activities as follows: ”Possible harmful reaction to the body which is not related to therapeutic effect. Toxicity can then be classified into (i) side effects (covered by pharmacodynamics and often predictable), (ii) reactions occurring as a result of overdose, over-duration, tolerance, dependence-addiction (covered either by pharmacodynamics and pharmacovigilance), (iii) hypersensitivity, allergic and idiosyncratic reaction (covered by pharmacovigilance), (iv) mid-term and long-term toxic effects (liver, renal, genotoxicity, teratogenecity, neurotoxicity, cardiotoxicity,…)”. It has been agreed that point (iv) is certainly the most important field for ‘omics predictive toxicology. Although not directly linked with eventual toxic properties of a given herb per se, the field of herb-drug interaction will also be investigated.

WP3 activities

In order to achieve its intended goals, the WP3 group has started a series of literature searches.

Topic 1: Aims at investigating the current status of functional genomics research on toxicology; this part of the literature search is centred on methods and related to prototype toxicants (“prototoxicants”). For each type of toxicity WP3 will investigate, current regulatory requirements for chemical drugs and herbs; current methods of evaluating this toxicity, and what is done at present regarding CHM; developments of “functional genomics” for this particular toxicity.

Topic 2: Aims at understanding the current status of toxicological knowledge on CHM (adverse effects and safety, including genotoxicity, teratogenicity, neurotoxicity, nephrotoxicity, hepatotoxicity). This part of the literature search (adverse effects and safety) is conducted on a series of “typical” CHM selected after examination of various herbs lists.


Topic 3: Aims at determining what is available in terms of pharmacovigilance and herb-drug interaction data. In addition to collecting clinical reports, experimental and theoretical reports will also be considered as (i) they may be able to spot a potential problem in advance from pre-clinical data; and (ii) they may not always be correct or useful for predicting problems, being sometimes misleading.

Interaction with other WPs

WP3 closely collaborates with WP5 (in vivo pharmacodynamic models); indeed functional genomics techniques used for assessing pharmacological activities and for investigating toxicity issues are closely related, even if endpoints can be different. A relationship with WP7 is developing as consumers and stakeholders will be approached by both groups.

Interaction with external bodies

WP3, in close cooperation with WP7 plans to approach the “consumers” potentially concerned with the problematic of CHMs safety (patient, therapist, importer, pharmacovigilance centers,…) and the stakeholders and regulatory bodies.

Potential WP impact

Guidance and coordination for toxicology studies of CHM will be proposed to ensure safety of the traditional remedies with complicated composition. WP3, in close collaboration with WP1, will focus on the safety issue of CHM, with an emphasis on the utilisation of functional genomics methodology. The approved best practice will be shared in the consortium to coordinate action and to be disseminated through publication on the consortium website and in scientific journals.

Possible contribution to the policy development and standards will be demonstrated through the following actions that will be basis for more thorough inventories:

  1. Compile a list of priority CHMs, in relationship with WP1 and WP2, so to concentrate efforts on important herbs.
  2. Define the meaning of “toxicity” and determine what should be covered by safety policies : (i) common safety issues for all herbs; (ii) side effects; (iii) herbs that are toxic only in overdosage; (iv) herbs toxic upon improper chronic use; (v) herbs incorrectly processed or used in incorrect combination with other herbs or at wrong dosages,….
  3. Compile relevant toxicological information and pharmacovigilance reports about CHMs, including a list of toxic herbal plants, CHM products, with their side effects, interactions with conventional drugs.
  4. Establish an inventory of well-known risk pharmacophores and CHMs possibly containing them.
  5. Compile available ‘omics information which have been used for evaluating the toxicity and safety of chemicals, drugs and herbal products, in view of proposing the development of  new  functional genomics approaches for the overall safety evaluation of CHMs.
WP3 Members:
Beneficiary members

Prof. Pierre Duez (WP3 Co-Coordinator, Université Libre de Bruxelles, Belgium)

Prof. Xinmin Liu (WP3 Co-Coordinator, Chinese Academy of Medical Sciences, China)

Dr. Hani El-Nezami (WP3 Assistant Coordinator, University of Hong Kong, China)

Prof. Alberto Dias (University of Minho, Portugal)

Prof. Yanjiang Qiao (Beijing University of Chinese Medicine, China)

Prof. Peter Hylands (King’s College London, UK)

Prof. Kelvin Chan (University of Sydney & University of Western Sydney, Australia)

Dr. Joëlle Nortier (Université Libre de Bruxelles, Belgium)

Prof. Caroline Stévigny (Université Libre de Bruxelles, Belgium)

Dr. Ling Dong (Beijing University of Chinese Medicine, China)

Prof. Yun Wang (Beijing University of Chinese Medicine, China)

Non-beneficiary members

Prof. Elizabeth Williamson (University of Reading, UK),

Prof. Zuguang Ye (China Academy of Chinese Medical Sciences, China)

Dr. Debbie Shaw (Guy’s & St Thomas’ NHS Foundation Trust, UK)

Prof. Y. James Kang (University of Louisville, USA)

Dr. Ning Wang (Public Research Centre of Health, Luxembourg)

Prof. Jean-Marie Colet (University of Mons, Belgium)

Prof. Ge Lin (The Chinese University of Hong Kong, China)

Prof. Olavi Pelkonen (University of Oulu, Findland)

Dr. Graeme Ladds (Pharsafer Associates Limited, UK)

Prof. Odd Georg Nilsen (Norwegian University of Science and Technology, Norway)

Prof. Thomas Efferth (University of Mainz, Germany)

Prof. Kahumba Byanga (University of Lubumbashi, Democratic Republic Of Congo)

Dr. Moustapha Ouedraogo (University of Ouagadougou, Burkina Faso)

WP3 Contact:

Prof. Pierre Duez

WP3 Co-coordinator

Laboratoire de Pharmacognosie, de Bromatologie et de Nutrition Humaine

Université Libre de Bruxelles

Campus de la Plaine – CP 205/9

Bd du Triomphe 1050 Bruxelles

Belgium

Tel:  +32 2 6505172

Fax: +32 2 6505430

E-mail: pduez@ulb.ac.be

Web page: http://www.ulb.ac.be/rech/inventaire/unites/ULB400.html

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