malaria nairobi 2006 creation and applicability of aamps [association for african medicinal plant...

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Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University of Pretoria, EU- CDE/EU-CTA and Ben-Erik van Wyk, Ameenah Gurib-Fakeem, Thomas Brendler, Denzil Phillips

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Page 1: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Creation and applicability of AAMPS [Association for African Medicinal Plant

Standards]

Kobus EloffPhytomedicine Programme, University of Pretoria, EU-CDE/EU-CTA

and

Ben-Erik van Wyk, Ameenah Gurib-Fakeem, Thomas Brendler, Denzil Phillips

Page 2: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Background• Sub-Saharan Africa contains c 60 000 plant species,

roughly 1/4 of world’s species• Trade of African medicinal plants in Europe very low

compared to species from India and China • Probably because no trading standards available• EU-Centre for the Development of Enterprise provided

funding to develop trade standards in order to create jobs in Africa

• Invited 9 leaders in African medicinal plant research to tender for project

Page 3: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Contract with CDE• Consortium JN Eloff, B-E van Wyk, GE Swan, R van

Brummelen• Get co-operation from scientists from rest of Africa and

from leading role players Europe• Identify most important African Medicinal Plants• Subcontract scientists to write profiles• Establish executive committee to oversee project Ben-

Erik van Wyk, Ameenah Gurib-Fakeem, Thomas Brendler, Denzil Phillips

Page 4: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Selection of priority species• List of more than 500 species selected from lists

of Herbal Products Association, Iwu, Brendler and publications by van Wyk, Iwu, Oliver-Bever, Hutchings, Gurib-Fakeem.

• Parameters used for selection: safety, efficacy, already widely used or good potential, possibility of cultivation, sustainable use, not threatened, different areas of Africa, not used as a narcotic.

Page 5: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

22 species selected round 1• Agathosma betulina A• Aloe ferox SA• Antidesma madagascariensis EA• Aphloia theiformis EA• Aspalathus linearis SA• Balanites aegyptica WA• Boswellia sacra NA• Cola nitida WA• Cyclopia genistoides SA• Danais fragrans EA• Harpagophytum procumbens SA

Page 6: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

23 species selected round 1 continued• Harungana madagascariensis EA• Hypoxis hemerocallidea SA • Kigelia africana EA• Moringa oleifera WA• Pelargonium sidoides SA• Prunus africana EA• Sceletium tortuosum SA• Siphonochilus aethiopicus SA• Sutherlandia frutescens SA• Warburgia salutaris SA• Xysmalobium undulatum SA

Page 7: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Validation and selection of rest • Additional funding received [CTA] workshop c

30 scientists, producers, exporters/importers from 17 countries

• To evaluate profiles developed• Select another c 27 species with the highest

priorities from list of c 73• Advise on further work

Page 8: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Outcome of workshop

• review and refine AMPS methodology • critically review the first 22 profiles prepared by the AMPS team• select a further 28 species for phase two of the AMPS project• select appropriate forms of international validation• recommend appropriate methods of dissemination• learn more about related research activities in Africa• develop long term linkages between workshop delegates• consider if AMPS can lead to an African Herbal Pharmacopoeia • started Association for African Medicinal Plant Standards

Page 9: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Living database• Information will be presented on website with

open access• Additional information evaluated & added• Closer cooperation academia industry• Will identify gaps---research projects• Will provide standards and lead to larger share

of market for African species• Provide more jobs, improve primary health care.

Page 10: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Managing Project

Executive Committee• Mr Denzil Phillips, Consultant CDE/CTA• Prof J N Eloff, University Pretoria• Prof A Gurib Fakeem, University Mauritius• Mr T Brendler, Germany• Prof B-E van Wyk, University Johannesburg

Page 11: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Profiles description General aspectsExample Siphonochiles aethiopicum

• 1. General description• Botanical name: • Siphonochilus aethiopicus (Schweinf.) B.L.Burtt • Main synonyms: Siphonochilus natalensis (Schltr. & K. Schum.) J.M.

Wood & Franks• Family: Zingiberaceae• Vernacular names: African ginger, wild ginger (English); isiphephetho,

indungulo (Zulu); gingembre Africaine (French); Afrikanischer Ingwer (German); zenzero Africano (Italian)

• Geographical distribution: Widely distributed in tropical Africa, from South Africa (Limpopo Province) northwards to Zambia, Malawi, Ethiopia, West Africa and Gambia.

• Conservation status: Said to be rare or extinct in KwaZulu-Natal and other parts of South Africa. Conservation status in other countries is not clear.]

Page 12: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Photographs B-E van Wyk

Rhizome and rootsPlant with flowers

Page 13: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Origin and preparation of plant material

• Origin: South Africa• Plant parts used: Rhizomes and fleshy roots.• Cultivated/wildcrafted: Product is available from

commercial plantations and rapid scale-up is possible. No wildcrafting should be allowed.

• Preparation/processing: The rhizomes and roots and simply sliced and dried.

• Flowering/harvesting time:• Rhizomes and roots are harvested at the end of the

growing season when the plants start to go dormant.

Page 14: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Identification and Quality Control

See introduction for methods used.• Plant material investigated:• dried, and powdered rhizome and roots• Extractability of dried material in mg/ml from 1 g

of plant material• Water 68• Ethanol 26• Acetone 17

Page 15: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Identification

TLC fingerprints western herbal medicines

Page 16: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Fingerprint Siphonochilis

• Solvent systems from left to right EMW, CEF, BEA. This separates polar compounds, intermediate polarity compounds and non-polar compounds

• Detection reagent vanillin-sulphuric acid.

Page 17: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Infra red scan of powder

Page 18: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Specialized TLC or HPLC if available

Standards methods of TLC can be used (similar to those for commercial ginger, Zingiber officinalis – see Van Beeck 1991). The essential oil fraction, containing the main furanoterpenoid, can be studied by GC using a published method (Viljoen et al. 2002).

Page 19: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Concentration active principle if known • The essential oil contains very high

concentrations (up to 0.2% of dry weight) of a single compound loosely referred to as Siphonochilus sesquiterpenoid or siphonochilone (Van Wyk et al. 1997, Holtzapfel et al. 2002, Viljoen et al. 2002). It is not clear if this compound is the active principle but it is a useful and unique marker substance for quality control.

OH

a-Terpineol

O

O

Siphonochilus sesquiterpenoid

Page 20: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Possible adulteration and mistaken identity

• Rare (unlikely). It may possibly be confused or adulterated with other members of the Zingiberaceae such as Zingiber or Hedychium but the difference is easily detected by TLC.

Page 21: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Standard specifications applied to most herbal medicines

• e.g. pesticide content, microbial load, ash and heavy metal content

• Acid-insoluble ash: Not more than 1%

• Water-soluble extractive: Not less than 15%

• Foreign matter: Not more than 1%

• Pesticide residues: national requirements

Page 22: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Stability of product

• Unstable in solution. Possibly stable in dry form. Stafford et al. (2005) reported that the antibacterial activity remained more or less unchanged while antiinflammatory activity decreased over time.

Page 23: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Formulation and dosage/Chemical constituents according to literature

• About 200 mg of dry rhizome is taken three or more times per day. In traditional medicine, a small piece of the fresh rhizome is chewed.

• The product is rich in essential oil (0.1-0.3% of fresh weight) and contains more than 70 monoterpenoids and sesquiterpenoids, including 1,8-cineole, cis-alloocimene, alpha-terpineol and germacrene B (to name only a few) (Viljoen et al. 2002). The main furanoterpenoid, siphonochilone, was reported to represent at least 20% of total composition of the oil (Van Wyk et al. 1997, Holzapfel et al. 2002, Viljoen et al. 2002).

Page 24: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Medicinal uses [traditional uses and uses described in pharmacopoeias]

• Fresh roots or rhizomes are chewed for coughs, colds and asthma.

• Tablets made from dried rhizomes or extracts are highly effective against tension headache, and also against influenza, sore throat, mild asthma, sinusitis, PMS and menstrual cramps.

• The main traditional uses in the Zulu culture were against malaria and Candida (Watt & Breyer-Brandwijk 1962, Cunningham 1988,

• Hutchings A et al. 1996, Van Wyk et al. 1997, Van Wyk & Gericke 2000, Crouch et al. 2000, Van Wyk & Wink 2004)

Page 25: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Known biological activities [pharmacological information]

• In vitro anti-inflammatory and uterine relaxing activities were reported (McGaw et

• al. 1997, Lindsay et al. 1999, Light et al. 2002). Extracts showed antibacterial

• activity, especially against Gram-positive bacteria, but no anti-viral effects (Light

• et al. 2002).

Page 26: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Toxicity • Literature No information• Brine shrimp toxicity assay LD50 =>

2000μg/ml.• Vero cell line LD50 0.409 μg/ml

Warnings, contraindications and side effects and interactions with other drugs

• None known. As a precaution, pregnancy and lactation are contraindicated but no published information exists.

Page 27: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Evaluation probable safety

• criteria based on Goldberg et al. Botanical Safety Handbook

• 1 Can be safely consumed when used appropriately.

• 2b Not to be used during pregnancy.[?]

• 2c Not to be used while nursing.[?]

Page 28: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Probable efficacy scale used

• ++! efficacy clinically proven, plant material with toxic potential

• + efficacy pharmacologically proven• +! efficacy pharmacologically proven, plant material

with toxic potential• +/- efficacy traditionally proven• +/-! efficacy traditionally proven, plant material with

toxic potential• - usage cannot be recommended because of risks

related• ? insufficient information for classification

Page 29: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Evaluaion probably efficacy• Anti-inflammatory + (McGaw et al. 1997, Light et al. 2002)• Anti-bacterial + (Light et al. 2002). • Uterine relaxing effects + (Lindsay et al. 1999)• Coughs, colds +/-• Tension headaches +/-• Influenza +/-• Sore throat +/-• Mild asthma +/-• Sinusitis +/-• PMS, menstrual cramps +/-• Malaria +/-• Candida +/-

Page 30: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Editorial Committee• Prof Arnold Vlietinck, Belgium• Prof P Houghton, UK• Members of Executive Committee

Page 31: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

AAMPS• Two delegates Ulrich Feiter and Tom Watson volunteered c €5000 to

start AAMPS. • AAMPS registered in Mauritius. The Centurion Lake declaration and a

press release was advertised widely and the information is available on two websites www.aamps.org and www.aamps.net.

• Published in the quarterly newsletter of WHO• Constitution written• Interim directors Prof Kobus Eloff [South Africa], Prof. Ameenah Gurib-

Fakeem [Mauritius], Prof Ermias Dagne [Ethiopia], Prof Ben-Erik van Wijk, [South Africa] Thomas Brendler,

• Main aim develop African Herbal Pharmacopoeia

Page 32: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Conclusion• This project has the potential of stimulating interest in

African medicinal plants.• Closer liaison between African Scientist and other role

players, win-win situation• Proper validation and evaluation critical for wide

acceptance and success of this project• Continued upgrading and correction of information is

one of major strengths of this approach

Page 33: Malaria Nairobi 2006 Creation and applicability of AAMPS [Association for African Medicinal Plant Standards] Kobus Eloff Phytomedicine Programme, University

Malaria Nairobi 2006

Thanks to sponsors, participants