ETHNOPHARMACOLOGY

1. ETHNOPHARMACOLOGY THE LINK BETWEEN ORTHODOX AND TRADITIONAL MEDICINE Obafemi .O. Johnson

2. Outline • Introduction to ethnopharmacology • Objectives of ethnopharmacology • General strategies/procedures for screening and evaluation of traditional medicines • Drug screening procedures • Pharmacological screening • Toxicity studies • Clinical trials • Conclusion

3. Introduction • Ethnopharmacology constitutes the study of plant, mineral and animal substances used to affect health other than orthodox medicine. • The prefix ‘ethno’ means preventive and therapeutic modalities other than western medicine • It is concerned with seeking rationale for use of traditional medicine handed down from generation to generation.

4. The subject is mainly concerned with the observation, description and experimental investigation of biological activity and the active substance of plants and animals used in traditional medicine of past and present cultures

5. Artemisinin, an antimalarial was obtained from Quinghaoso, (Artemisia annua) a plant used for treatment of malaria in china • NIPRISAN, a drug developed by NIPRID for the management of sickle cell anaemia, was discovered from a herbal preparation in Nigeria.

6. TRADITIONAL MEDICINE Tangible components Non tangible components

7. Tangible components - plants, minerals and animal materials for the prevention and treatment of disease - the practice of some surgical procedures such as circumcision, bone setting, TBA’s e.t.c.

8. non tangible components • Spiritism, incantations and rituals

9. Ethnopharmacology does not evaluate the non- tangible components of traditional medical practice

10. Ethnopharmacology is a multidisciplinary study that encompasses: • Western/botanical and ethnotaxonomic classifications • Assessments of how plants are perceived and used in varied sociocultural contexts • Constituent analyses and investigations of pharmacological activities • Examinations of the physiological or clinical impact of plant use on human health

11. Ethnopharmacology is a multidisciplinary field involving various professionals such as botanists, pharmacologists, pharmacognosists, chemists, physiologists, pathologists, toxicologists, pharmacists, medical doctors.

12. Objectives of Ethnopharmacology • To establish a realistic approach to traditional medicine so as to promote and further contribute to modern medical practice • To explore the resources of traditional medicine in the light of modern science with a view to rationalise the most effective and useful tehniques while discouraging dangerous practices

13. Objectives of Ethnopharmacology cont’d • To promote the integration of sound knowledge and experimentation techniques both in traditional and modern medicine • To encourage collaboration amongst researchers world wide in the determination of the effectiveness of plants and their medical utilization.

14. General strategies for screening and evaluation of traditional medicines • Literature Survey • Plant Selection • Plant collection and processing • Drug screening procedures

15. Literature Survey • A comprehensive literature survey must be carried out prior to any biological testing in screening of traditional medicines • Literature survey is essential to obtaining information on previous works on plants, various uses for the plants in different parts of the world, whether the plants are widespread or found in few areas, whether they are known to be toxic or not

16. Literature survey involves the browsing of scientific journals • Computerised data bases completely or partially devoted to traditional medicine are available and make literature search more effective. e.g. NAPRALERT, AFLORA, PHARMEL

17. Plant Selection • After thorough literature survey, the plant to investigate must be selected • Involves the decision on which material to collect and on what basis

18. Priority should be given to plants that already have evidence of safety and efficacy based on local use or published data

19. Plant selection can be based on the following: • Folkloric Information • Presence of phytochemical Constituents • Combination of folkloric information and presence of phytochemical constituents • Blind random selection

20. Plant collection and processing • After plant selection, botanical identity must be established and site for their procurement located. Voucher specimen must be preserved and the number given • Plant must be collected at the appropriate time and season as chemical constituents of plants vary from season to season or at different times of the day. (must be stated) • Plant collection must be done carefully to minimise adulteration

21. In Processing, drying should not be done under direct sunlight and to avoid photolysis leading degradation of active principles. Shade drying is more effective. • Crude extraction involving the use of solvents is carried out to extract the active principle. Solvents used can be polar e.g. ethanol, water or non-polar e.g. pet. ether • Extract can then be freeze dried or evaporated to dryness, wrapped in aluminium foil and properly stored

22. Drug screening procedures The stages involved in the development of medicinal substances include: • Evaluation of literature data (screening and evaluation procedure) • Animal experiments (preclinical screening) -pharmacological screening -toxicological screening • Formulation studies • Clinical trials (Clinical screening)

23. Evaluation of literature data (screening and evaluation procedure) • To obtain up-to-date information on screening and evaluation methods/procedures • Gives valuable information on possible pharmacological properties (previous synthesis, SARs, previous isolation e.t.c.) • Helps to prevent duplication of previous studies on same materials

24. Pharmacological screening and evaluation procedures • Involves designing animal experiments in a manner that will yield maximum information relevant to human physiology and disease. • Proper experimental model for pharmacological screening should be based on simplicity, rapidity, reproducibility and cheapness

25. Certain factors can modify pharmacological effects in experimental animals viz: • Dose of the agent • Route of administration • Season, environmental temperature and humidity • Day and night cycle • Psychological stress influencing the animals • Health condition of laboratory animals • Age and body weight of lab. Animals • Species differences • Genetic factors • Sex differences

26. Some problems of pharmacological screening include: • Variation from sample to sample • Unexpected dose-response relationships • Variation within samples from the same batch of plant material • Failure to obtain positive results with an extract containing known active principles

27. Pharmacological screening and evaluation procedures Based on physiological responses /techniques, pharmacological screening is generally classified into two viz: -Quantitative techniques -Qualitative techniques

28. Quantitative techniques • Mainly dose-response relationships • Mostly determined by using the increasing physiological response of an organism induced by increasing doses of a test substance • Sometimes however, it is impossible to obtain a dose-dependent response • Dose response curves give valuable information about the specificity of an effect, mechanism of action, efficacy determination • Also useful for ED50 determination

29. Qualitative techniques • Generally used for preliminary pharmacological screening • The aim is generally limited to understanding whether the agent under investigation has effect on a certain physiological system or not • Easier and less expensive than quantitative techniques

30. Phases of pharmacological screening • Primary screening • Secondary screening • Tertiary screening

31. Primary pharmacological screening Pharmacological screening procedures are categorised into 4 depending on the objectives of the project: • Simple screen/single goal screen • Blind screen/broad based • Programmed screening • Mechanism based screens

32. Simple screen/single goal screen • Here, a pharmacological model or test are used to screen plants for a particular pharmacological activity. E.g. tests for analgesia, hypoglycemic activity • The objective here is to use suitable sufficently accurate methods rather than a battery of tests • Sometimes involves running multiple plants through the same pharmacological model • It is a useful way to screen natural products with long traditional use in a particular disease

33. Blind screen/broad based • Employs a battery of tests to cover a broad area of biological activity i.e. the extract/natural product is being investigated for various pharmacological activities • Is a technique that can be used for detecting pharmacological activity in a group of substances with no history of use • Feng & associates in 1962 utilized 7 different isolated organ preparations to screen aqeous extracts of about 55 west indian plants • Obsolete

34. Programmed screening • Programmed screen is midway between the simple screen and blind screen • Here, a programme of testing using a battery of tests is employed but with the aim of screening is more limited than for blind screening • Greater precision in the results is expected

35. Mechanism based screens • Utilises the knowledge of molecular and biochemical basis for pathogenesis of disease • Involves choosing molecular targets for the inhibition of disease progression and natural products are screened based on these • They are becoming important bioassays for natural products due to their specificity, ability to handle very large number of samples, use of in-vitro systems

36. Secondary pharmacological screening • If promising activity has been found in primary screening, then a sizeable quantity of authenticated material is acquired and secondary screening conducted • Seeks to confirm in another specie of laboratory animals the activity noted in the primary screen • Should be standardised so as to allow comparisons with clinically useful library drugs

37. Should be conducted using either solvent free extractives or semi pure/pure chemical • This screening is carried out to support a major decision which must be given at the end of this phase {whether the plant is worth more investigating & development}

38. Tertiary pharmacological screening Consists of : • Chemical structure determination • Classical pharmacological research • Toxicological research

39. Involves many expert (and expensive) scientists who will have to work together in a team effort • Therefoer must be carried out using only chemically pure material hence larger ammounts of authenticated crude material will be required on a regular basis until a synthetic or semi synthetic procedure can be developed • Never really ceases even after the drug is released for sale because there always remains some facet left unexplained and open for f • Expensive and time consuming

40. Follow up studies • Usually undertaken once a standardised extract or pure compound shows promising activity (i.e. after pri, sec & tert screen). • They include studies on: -Specific pharmacological action -General pharmacology -pharmacokinetics

41. Toxicity Studies Tests for the possible harmful effects of the compound. • Acute toxicity (LD50) • Sub acute toxicity {behavioural, biochemical and histological studies} • Chronic toxicity {same as above} • Teratogenicity • Mutagenicity • Carcinogenicity • Reproductive studies

42. Formulation • After discovery and pharmacological and toxicological studies, the new drug must be presented in a form that will be most acceptable for consumption • This is the role of the pharmacist • The pharmacokinetics of the drug must be given due consideration in the formulation

43. Clinical trials • This involves the testing of the new herbal drug in humans • Permission must be obtained from regulatory authorities i.e. the national regulatory agency such as NAFDAC, FDA and the appropriate ethics committee • An informed consent must be obtained from all participants

44. Clinical trials involve several phases viz: • Phase I (Clinical pharmacology trial) • Phase II (Exploratory clinical trial) • Phase III (Multicentric clinical trial) • Phase IV (Post marketing surveillance)

45. Clinical trials Phase 1 • This is clinical pharmacology phase • Performed in healthy male volunteers • Intended to establish preliminary evaluation of safety data on pharmacodynamic effects including ADRs and initial pharmacokinetic data • Clinical, physiological, biochemical and haematological parameters are monitored by trained investigators • Double blind studies

46. Clinical trials Phase 2 • Called the exploratory phase • Aimed to demonstrate activity and assess short-term safety in patients suffering from disease for which the product is intended • Makes use of limited number of patients to establish therapeutic utility, dosage schedule and possible side effects • Additional pharmacokinetic data is also generated • Study usually limited to one or two centers and 20-50 patients depending on the drug

47. Clinical trials Phase 3 • Called multicentric clinical trial/confirmtory trial • Should generate sufficient data about the safety and efficacy in comparison with a standard drug • Spread over several centers and covers larger and varied patient groups (about 500 patients) • Additional studies may be required in special cases such as elderly patients, hepatic, renal or cardiac complications

48. Phase 4 • Called post-marketing surveillance • Performed after marketing the new product and based on the product characteristics on which market authorisation was obtained • The same scientific and ethical guidelines are used as in pre-marketing

49. Conclusion • World is going for naturals; herbal medicines/ remedies in health care to fight diseases • There are millions of plants yet unscreened • Research in ethnopharmacology by young pharmacists in the making like YOU is encouraged