BASELINE CHEMICAL STUDIES THAT AID IN THE DEVELOPMENT OF ESSENTIAL OIL AND MEDICINAL PLANT INDUSTRY IN AFRICA
Ermaia Dagne
Department of Chemistry, Addis Ababa University, P.O. Box 30270, Addis Ababa, Ethiopia, Fax 2511 551244.
INTRODUCTION
Africa's diverse topography provides habitats with a wealth of genetic and species diversity, among them a rich endemic flora with diverse therapeutic and other uses. The use of medicinal plants for traditional health care in communities of developing countries goes back a long way and can be considered a living tradition. Medicinal plants have always been of interest to communities in such countries since these plants are used by them on a daily basis. Modern medicine is also showing growing interest in medicinal plants resulting in a rise of demand for such products in the developed world. However, much of the ethnomedical heritage of Africa is yet to be documented and studied. Access to ethnomedical information is generally obtained from herbalists or from open markets where medicines are customarily sold side by side with spices and other food items. As part of this heritage is shrouded in mystery, the challenge of the day is to intensify systematic studies on the botany, chemistry and pharmacology of medicinal plants in order to develop the useful aspects of traditional medicine and promote its gradual integration into the modern public health care system. Such studies will also contribute to reducing quackery and introducing concepts of formulation of drugs, standardized dosages, and adherence to hygienic practices.
The main aim of this paper is to suggest strategies for enhancing the role of research towards the accelerated development of a medicinal and aromatic plants industry in Africa.
Current Status of Phytochemical Research on African plants
It is estimated that about 85% of the population in Africa rely on traditional medicine for their health care. The African pharmacopoeia (OAU/STRC, 1985) which deals mainly with medicinal plants has identified and described over 100 such plants. This admirable work is part of an attempt to establish a scientific basis for the development of an African pharmaceutical industry based mainly on medicinal plants.
An overview of the current status from our database
At the present time, much effort is directed by the scientific community from Africa and else towards the study of the botany, chemistry and pharmacology of African plants and considerable amount of information is now available in the literature. It is important to keep abreast of these developments in order to draw lessons of relevance to the establishment of medicinal plant industry.
The database that we are building on results of phytochemical studies on plants originating from Africa and appearing in leading natural products journals clearly shows the rise in the number of scientific reports on the chemistry of African plants. Nearly 1500 papers were published on African plants in he well known international journal Phytochemistry in the period 1963-97. In the same period nearly 1000 papers appeared on African Plants in the other two natural products journals namely J. Nat. Prod. And Planta Medica. Large numbers of reports were on plants from South Africa (370), Egypt (360), Ethiopia (300), Nigeria (250), Kenya (200) and Cameroon (150).
Our database has now nearly 6000 entries on the phtochemical, botanical and pharmacological aspects of African medicinal and other plants, enabling us to offer limited literature service to requesting parties. Typically most of the chemistry oriented papers report on isolation and characterization of novel compounds from the African flora. Others deal with the biological and pharmacological activities of crude extracts or isolated compounds. The choice of plants is sometimes based on folk medicine, use in commerce, chemotaxonomic significance and biological activities. In the biologically inclined studies workers undertake their research either as part of drug discovery program or simply to find out if there is a scientific basis in the traditional claims for the use of the plants as medicines.
Finding scientific rationale for use of common medicinal plants: The case of Taverniera abyssinica
The roots of medicinal plant popularly known in Amharic as dingetegna, "medicine for sudden illness" are sold in the markets of Ethiopia. It was not straight forward to link the roots sold in the market to the living plant, without which it is not possible to establish its botanical identity. Indeed this is a typical scenario that one faces when dealing with plants purchased in markets. It was possible to get proper specimens needed for the establishment of the botanical identity of the plant only with the aid of an ethnobotanist and only then could it be identified as the endemic Taverniera abyssinica (Leguminosae). Pharmacological studies on the extract of the roots showed that it antagonizes the contractile responses of the guinea-pig ileum to acetylcholinea and histamine (Noamesi et al., 1990). The crude extracts as well as pterocarpan constituents (Duddeck et al., 1987) of the roots of this plant wwere also shown to exhibit significant analgesic and antipyretic properties (Dagne et al., 1990). These studies offer physiological basis for the widespread ethnomedical uses of the plant to treat stomachache and reduce fever.
Smoked and inhaled medicines
Contemporary specialists in botanical medicines emphasize the burning of plants in order to use smoke as a therapeutic vehicle. Smoke may be inhaled or used to fumigate the whole house to get rid of insects and parasites. Fumigating part of the body by burning plants is also common in
Africa.
Among smoking plants available in many medicinal plant markets of Ethiopia, the most common is the root of Echinops kebericho (Compositae) which is used usually to fumigate the body as a general medicinal and also to rid a house of pests and insects. Abegaz et al. (1991) isolated fromteh roots of this plant, dehydrocostus lactone (2). The above compounds was recently reported as the active constituents of a Japanese herbal medicine mokko by Taniguchi et al. (1995).
We have shown by GC analysis that when this plant is burned, dehydrocostus lactone is the major component of the smoke. It is clear that during fumigation the smoke is a good vehicle for the bioactive compound.
Other fumigants commonly available in markets and used for various purposes include: bark of Croton macrostachyus (Euphorbiaceae), aerial parts of Otostegia intefrigolia (labiataea), roots of Silene macrosilene (Caryophyllaceae) and stem of Olea europaea subsp. Africana (Oleaceae).
A very popular household inhaled medicine against spontaneous rash and fever is a plant locally known as damakese or Ocimum lamifolium (Labitaeae), a plant widely grown in home gardens. The leaves are squeezed between the hands and the essence inhaled for a long time, or mixed with water of coffee and taken orally as medicine against rash and allergy. GC analysis of the essential oil of the leaves shows it to be quite rich in secondary metabolites. However, much chemical and biological work remains to be done on this interesting plant.
Chemical Study of African Plants: A rewarding experience
It is important for African scientists to identify the most important plants of Africa and to undertake chemical research on them. A fitting example for this is the genus Aloes, of which there are 450 species in Africa. A. vera is now cosmopolitan and is cultivated in many parts of the world, while A. ferox occurs abundantly in he wild in South Africa. A review of the literature on the chemistry of Aloe (Dagne, 1996) shows that there are many research groups actively working on he chemistry of members of this genus. Our studies of a number of species from Ethiopia and South Africa (Dagne et al., 1996) has resulted in the isolation and characterization of a number of novel substances. Among many such compounds we characterized, the structure of a representative compound which we named littoraloin (1)
The above example illustrates that chemical works on African plants is not only challenging but also quite rewarding when one takes into account the frequency at which novel compounds are isolated.
Challenges in R & D on African Medicinal Plants
African medicinal plants resources may be doomed to extinction by overexploitation resulting from excessive commercialization, habitat destruction and other natural and man made destructive influences unless energetic conservation measures are taken that ensure their continued availability. This can be done through the establishment of medicinal plant gardens and farms. Such projects should also focus on processing of medicinal plants so that they are not limited to delivery in only raw form to local and international markets.
Value adding to raw materials: An urgent agenda
Many plants originating from Africa have become sources of important drugs. Many international companies important African plants cultivated or collected form the wild and process drugs from them. Madagascar is among the African countries that export significant amounts of medicinal and aromatic plants. In the 1976-1988 period 84,2339.9 tons of six major medicinal plants were exported from Madagascar for a total sales of US$ 3,472,500, which is about $40 per ton or 4 cents per kg (Rajaonarivony, 1996). It is obvious how incredibly low the return is compared to what would have been gained had some efforts been geared towards enhancing the value of the products by some form of processing.
Palmora oil is obtained by steam distillation of Cymbogon maritinii. In Ethiopia the oil is produced mainly for local consumption by the Essential Oil.
Research centre of the Ministry of Trade and Industry, which sells it for ca. $10/kg. GC analysis of the essential oil (See Fig. 1) shows geraniol to be the main component, and it may be present in the oil to the extent of 50-80%. It is possible to get commercial grade geraniol with a purity of he order of 95 - 98% by fractional distillation of he essential oil. In that case the return may be as high as $250/kg. Geranyl acetate which is even more valuable is another desired product that can be obtained in pure form during the fractional distillation or by acetylating the geraniol.
Equally interesting is the xase of the natural oleo-gum resin, franckincense and myrrh, which are obtained from Boswellia and Commiphora species respectively. These plants are mainly found in the Horn of Africa with a few species scattered in Arabia and India. The principal frankincense producing series are: B papryfera, B. neglecta and B. rivae occurring in Ethiopia, B. sacra (syn B. carteri) and B. frereanan in Somalia and B. serrata in India. The major frankincense suppliers of the world today are Ethiopia, Somalia and Kenya. France, Germany and China are the major buyers, for using the resin in cosmetics and in the case of China for the preparation of traditional medicines. Myrrh has been employed as incense and for embalming purposes since ancient times. It is employed in formulations of perfumes since it blends well with geranium, musk and patchouli. It is also known to impart pleasant aromatic flavour to mouthwashes and toothpaste. However, hardly any effort has been made towards adding value to these natural products in particular in those countries where the resin-producing trees are found in abundance. By value-added processing, communities in these countries would have earned more income from the resins and thereby become more aware of the value of conserving the trees.
Each medicinal and aromatic plant that is used in abundance in local and export markets should be thoroughly studied and continually monitored for composition of its constituents. It is therefore of paramount importance to enhance Africa's capacity to do this. Only then would it be possible to seek ways and means of adding value to these resources.
Increasing local support for R & D.
Governments in Africa should be made to realize that the future well being of the people depends very much on how well we invest in research and education. Just as a company that does not invest in R & D will not remain competitive, a society that does not invest in research and education will also have very little chance of prospering. Little input is at the moment forthcoming from local sources for research and development of medicinal and aromatic plants. Much of the meager support is obtained from external resources and it is therefore important that there should be matching fund from within.
Networking as a strategy for promoting R & D activities.
The majority of natural products chemists in Africa are, in the main, limited to work without access to expertise for identification of the constituents of medicinal and other plants of interest. They are often forced to work in the absence of or with inadequate facilities, particularly modern equipment as well as the manpower and technical resources of maintaining the. Under such circumstances the researchers are forced to seek the assistance of laboratories in developed countries. This situation coupled with inadequate financial resource's is a serious stumbling block to the development of natural products research in the continent. Furthermore, existing establishments lack efficient administrative set ups that are so essential for the smooth running or research programs. In short the required fund is most of the time not available, and when it is there, the mechanism is not in place to effectively utilize it
An important means of enhancing capability is to share resources and facilities through networking at local, regional and international levels. Our experience (Dagne, 1996b) with the organization and coordination or the Natural Products Research Network for Eastern and Central Africa (NAPRECA), showed that much of the problems of isolation, lack of facilities, lack of forum for disseminating results etc could be alleviated through networking. Exchange schemes and short tem training programs organized by networks also go far in developing the capability of research staff. Network of the future should not only be made up of researchers but should also include entrepreneurs and businessmen as well as NGOs, traditional healers and members of the community.
CONCLUSIONS
If a medicinal plant industry is to thrive in the future in Africa, much emphasis should be given now to research that focuses on the generation of baseline information on medicinal and aromatic plants. Only then will it be possible to develop products that will satisfy consumers who usually shop around form country to country because they seek products of high quality and efficacy. In this regard tomorrow's winners will be those who invest today in natural products research by allocating resources for research capacity building and manpower development. Furthermore, networks in developing countries could also play a pivotal role in acclereting development of medicinal and aromatic plants industry in Africa.
REFERENCES
Abegaz, B.M., Tadesse, M. and Majinda, R. (1991). Distribution of swsquiterpene lactones and polycetaylenic thiophenes in Echinop. Biochemical systematics & Ecology 19: 323-328.
Dagne, E., Yesnesew, A., Capasso, F., Macolo, N. and Pinto, A. (1990).. Preliminary studies on antipyretic and analgesic properties of Taverniera abyssinica. Ethiopian Medical Journal. 28: 1551-161
Dagne, E., Van Wyk, b.-E, Stephenson, D. and Steglich, W. (1996). Three axanthrones from Aloe littoralis. Phytochemistry, 42: 1683-1687.
Dagne, E., (1996a). Review of the chemistry of Aloes of Africa. Bulletin of the Chemical of Ethiopia, 10: 89-103
Dagne, E., (1996b). NAPRECA and its Role in the Dissemination of Information on Natural Products Research in Africa. In "Bridge Builders". National Academy Press, Washington D.C.. pp. 217-231
Duddeck, H., Yenesew, A. and Dagne, E. (1987). Isoflavonoids from Taverniera abyssinica. Bulletin of the Chemical Society of Ethiopia 1:36-41
Noamesi, B.K., Bogale, M. and Dagne, E. (1990). Intestinal smooth muscle spasmolytic actions of the aqueous extract of the roots of Taverniera abyssinica. Journal of Ethnopharmacology.
OAU-STRC (1985). African Pharmacopoeia. OAU - STRC, Lagos.
Rajaonarivony, J.I.M. (1996). The Implementation of a Governmental Policy in Natural Products Research and Development in Madagascar. In "Science and Africa: Utilizing Africa's Genetic Affluence through Natural Products Research and Development." AAAS Symposium, Washington D.C. pp83-98.
Taniguchi, M., Kataoka, T. Suzuki, H., Uramoto, M. Ando, M., Arao, K.. Magae, J., Nishmura, T., Otake, N. and Nagai, K. (1995). Costunolide and dehydrocostus lactone as inhibitors of killing function of cytotoxic Tlymphocytes. Bioscience, Biotechnology and Biochemistry. 59:2064-2067.
Ermaia Dagne
Department of Chemistry, Addis Ababa University, P.O. Box 30270, Addis Ababa, Ethiopia, Fax 2511 551244.
INTRODUCTION
Africa's diverse topography provides habitats with a wealth of genetic and species diversity, among them a rich endemic flora with diverse therapeutic and other uses. The use of medicinal plants for traditional health care in communities of developing countries goes back a long way and can be considered a living tradition. Medicinal plants have always been of interest to communities in such countries since these plants are used by them on a daily basis. Modern medicine is also showing growing interest in medicinal plants resulting in a rise of demand for such products in the developed world. However, much of the ethnomedical heritage of Africa is yet to be documented and studied. Access to ethnomedical information is generally obtained from herbalists or from open markets where medicines are customarily sold side by side with spices and other food items. As part of this heritage is shrouded in mystery, the challenge of the day is to intensify systematic studies on the botany, chemistry and pharmacology of medicinal plants in order to develop the useful aspects of traditional medicine and promote its gradual integration into the modern public health care system. Such studies will also contribute to reducing quackery and introducing concepts of formulation of drugs, standardized dosages, and adherence to hygienic practices.
The main aim of this paper is to suggest strategies for enhancing the role of research towards the accelerated development of a medicinal and aromatic plants industry in Africa.
Current Status of Phytochemical Research on African plants
It is estimated that about 85% of the population in Africa rely on traditional medicine for their health care. The African pharmacopoeia (OAU/STRC, 1985) which deals mainly with medicinal plants has identified and described over 100 such plants. This admirable work is part of an attempt to establish a scientific basis for the development of an African pharmaceutical industry based mainly on medicinal plants.
An overview of the current status from our database
At the present time, much effort is directed by the scientific community from Africa and else towards the study of the botany, chemistry and pharmacology of African plants and considerable amount of information is now available in the literature. It is important to keep abreast of these developments in order to draw lessons of relevance to the establishment of medicinal plant industry.
The database that we are building on results of phytochemical studies on plants originating from Africa and appearing in leading natural products journals clearly shows the rise in the number of scientific reports on the chemistry of African plants. Nearly 1500 papers were published on African plants in he well known international journal Phytochemistry in the period 1963-97. In the same period nearly 1000 papers appeared on African Plants in the other two natural products journals namely J. Nat. Prod. And Planta Medica. Large numbers of reports were on plants from South Africa (370), Egypt (360), Ethiopia (300), Nigeria (250), Kenya (200) and Cameroon (150).
Our database has now nearly 6000 entries on the phtochemical, botanical and pharmacological aspects of African medicinal and other plants, enabling us to offer limited literature service to requesting parties. Typically most of the chemistry oriented papers report on isolation and characterization of novel compounds from the African flora. Others deal with the biological and pharmacological activities of crude extracts or isolated compounds. The choice of plants is sometimes based on folk medicine, use in commerce, chemotaxonomic significance and biological activities. In the biologically inclined studies workers undertake their research either as part of drug discovery program or simply to find out if there is a scientific basis in the traditional claims for the use of the plants as medicines.
Finding scientific rationale for use of common medicinal plants: The case of Taverniera abyssinica
The roots of medicinal plant popularly known in Amharic as dingetegna, "medicine for sudden illness" are sold in the markets of Ethiopia. It was not straight forward to link the roots sold in the market to the living plant, without which it is not possible to establish its botanical identity. Indeed this is a typical scenario that one faces when dealing with plants purchased in markets. It was possible to get proper specimens needed for the establishment of the botanical identity of the plant only with the aid of an ethnobotanist and only then could it be identified as the endemic Taverniera abyssinica (Leguminosae). Pharmacological studies on the extract of the roots showed that it antagonizes the contractile responses of the guinea-pig ileum to acetylcholinea and histamine (Noamesi et al., 1990). The crude extracts as well as pterocarpan constituents (Duddeck et al., 1987) of the roots of this plant wwere also shown to exhibit significant analgesic and antipyretic properties (Dagne et al., 1990). These studies offer physiological basis for the widespread ethnomedical uses of the plant to treat stomachache and reduce fever.
Smoked and inhaled medicines
Contemporary specialists in botanical medicines emphasize the burning of plants in order to use smoke as a therapeutic vehicle. Smoke may be inhaled or used to fumigate the whole house to get rid of insects and parasites. Fumigating part of the body by burning plants is also common in
Africa.
Among smoking plants available in many medicinal plant markets of Ethiopia, the most common is the root of Echinops kebericho (Compositae) which is used usually to fumigate the body as a general medicinal and also to rid a house of pests and insects. Abegaz et al. (1991) isolated fromteh roots of this plant, dehydrocostus lactone (2). The above compounds was recently reported as the active constituents of a Japanese herbal medicine mokko by Taniguchi et al. (1995).
We have shown by GC analysis that when this plant is burned, dehydrocostus lactone is the major component of the smoke. It is clear that during fumigation the smoke is a good vehicle for the bioactive compound.
Other fumigants commonly available in markets and used for various purposes include: bark of Croton macrostachyus (Euphorbiaceae), aerial parts of Otostegia intefrigolia (labiataea), roots of Silene macrosilene (Caryophyllaceae) and stem of Olea europaea subsp. Africana (Oleaceae).
A very popular household inhaled medicine against spontaneous rash and fever is a plant locally known as damakese or Ocimum lamifolium (Labitaeae), a plant widely grown in home gardens. The leaves are squeezed between the hands and the essence inhaled for a long time, or mixed with water of coffee and taken orally as medicine against rash and allergy. GC analysis of the essential oil of the leaves shows it to be quite rich in secondary metabolites. However, much chemical and biological work remains to be done on this interesting plant.
Chemical Study of African Plants: A rewarding experience
It is important for African scientists to identify the most important plants of Africa and to undertake chemical research on them. A fitting example for this is the genus Aloes, of which there are 450 species in Africa. A. vera is now cosmopolitan and is cultivated in many parts of the world, while A. ferox occurs abundantly in he wild in South Africa. A review of the literature on the chemistry of Aloe (Dagne, 1996) shows that there are many research groups actively working on he chemistry of members of this genus. Our studies of a number of species from Ethiopia and South Africa (Dagne et al., 1996) has resulted in the isolation and characterization of a number of novel substances. Among many such compounds we characterized, the structure of a representative compound which we named littoraloin (1)
The above example illustrates that chemical works on African plants is not only challenging but also quite rewarding when one takes into account the frequency at which novel compounds are isolated.
Challenges in R & D on African Medicinal Plants
African medicinal plants resources may be doomed to extinction by overexploitation resulting from excessive commercialization, habitat destruction and other natural and man made destructive influences unless energetic conservation measures are taken that ensure their continued availability. This can be done through the establishment of medicinal plant gardens and farms. Such projects should also focus on processing of medicinal plants so that they are not limited to delivery in only raw form to local and international markets.
Value adding to raw materials: An urgent agenda
Many plants originating from Africa have become sources of important drugs. Many international companies important African plants cultivated or collected form the wild and process drugs from them. Madagascar is among the African countries that export significant amounts of medicinal and aromatic plants. In the 1976-1988 period 84,2339.9 tons of six major medicinal plants were exported from Madagascar for a total sales of US$ 3,472,500, which is about $40 per ton or 4 cents per kg (Rajaonarivony, 1996). It is obvious how incredibly low the return is compared to what would have been gained had some efforts been geared towards enhancing the value of the products by some form of processing.
Palmora oil is obtained by steam distillation of Cymbogon maritinii. In Ethiopia the oil is produced mainly for local consumption by the Essential Oil.
Research centre of the Ministry of Trade and Industry, which sells it for ca. $10/kg. GC analysis of the essential oil (See Fig. 1) shows geraniol to be the main component, and it may be present in the oil to the extent of 50-80%. It is possible to get commercial grade geraniol with a purity of he order of 95 - 98% by fractional distillation of he essential oil. In that case the return may be as high as $250/kg. Geranyl acetate which is even more valuable is another desired product that can be obtained in pure form during the fractional distillation or by acetylating the geraniol.
Equally interesting is the xase of the natural oleo-gum resin, franckincense and myrrh, which are obtained from Boswellia and Commiphora species respectively. These plants are mainly found in the Horn of Africa with a few species scattered in Arabia and India. The principal frankincense producing series are: B papryfera, B. neglecta and B. rivae occurring in Ethiopia, B. sacra (syn B. carteri) and B. frereanan in Somalia and B. serrata in India. The major frankincense suppliers of the world today are Ethiopia, Somalia and Kenya. France, Germany and China are the major buyers, for using the resin in cosmetics and in the case of China for the preparation of traditional medicines. Myrrh has been employed as incense and for embalming purposes since ancient times. It is employed in formulations of perfumes since it blends well with geranium, musk and patchouli. It is also known to impart pleasant aromatic flavour to mouthwashes and toothpaste. However, hardly any effort has been made towards adding value to these natural products in particular in those countries where the resin-producing trees are found in abundance. By value-added processing, communities in these countries would have earned more income from the resins and thereby become more aware of the value of conserving the trees.
Each medicinal and aromatic plant that is used in abundance in local and export markets should be thoroughly studied and continually monitored for composition of its constituents. It is therefore of paramount importance to enhance Africa's capacity to do this. Only then would it be possible to seek ways and means of adding value to these resources.
Increasing local support for R & D.
Governments in Africa should be made to realize that the future well being of the people depends very much on how well we invest in research and education. Just as a company that does not invest in R & D will not remain competitive, a society that does not invest in research and education will also have very little chance of prospering. Little input is at the moment forthcoming from local sources for research and development of medicinal and aromatic plants. Much of the meager support is obtained from external resources and it is therefore important that there should be matching fund from within.
Networking as a strategy for promoting R & D activities.
The majority of natural products chemists in Africa are, in the main, limited to work without access to expertise for identification of the constituents of medicinal and other plants of interest. They are often forced to work in the absence of or with inadequate facilities, particularly modern equipment as well as the manpower and technical resources of maintaining the. Under such circumstances the researchers are forced to seek the assistance of laboratories in developed countries. This situation coupled with inadequate financial resource's is a serious stumbling block to the development of natural products research in the continent. Furthermore, existing establishments lack efficient administrative set ups that are so essential for the smooth running or research programs. In short the required fund is most of the time not available, and when it is there, the mechanism is not in place to effectively utilize it
An important means of enhancing capability is to share resources and facilities through networking at local, regional and international levels. Our experience (Dagne, 1996b) with the organization and coordination or the Natural Products Research Network for Eastern and Central Africa (NAPRECA), showed that much of the problems of isolation, lack of facilities, lack of forum for disseminating results etc could be alleviated through networking. Exchange schemes and short tem training programs organized by networks also go far in developing the capability of research staff. Network of the future should not only be made up of researchers but should also include entrepreneurs and businessmen as well as NGOs, traditional healers and members of the community.
CONCLUSIONS
If a medicinal plant industry is to thrive in the future in Africa, much emphasis should be given now to research that focuses on the generation of baseline information on medicinal and aromatic plants. Only then will it be possible to develop products that will satisfy consumers who usually shop around form country to country because they seek products of high quality and efficacy. In this regard tomorrow's winners will be those who invest today in natural products research by allocating resources for research capacity building and manpower development. Furthermore, networks in developing countries could also play a pivotal role in acclereting development of medicinal and aromatic plants industry in Africa.
REFERENCES
Abegaz, B.M., Tadesse, M. and Majinda, R. (1991). Distribution of swsquiterpene lactones and polycetaylenic thiophenes in Echinop. Biochemical systematics & Ecology 19: 323-328.
Dagne, E., Yesnesew, A., Capasso, F., Macolo, N. and Pinto, A. (1990).. Preliminary studies on antipyretic and analgesic properties of Taverniera abyssinica. Ethiopian Medical Journal. 28: 1551-161
Dagne, E., Van Wyk, b.-E, Stephenson, D. and Steglich, W. (1996). Three axanthrones from Aloe littoralis. Phytochemistry, 42: 1683-1687.
Dagne, E., (1996a). Review of the chemistry of Aloes of Africa. Bulletin of the Chemical of Ethiopia, 10: 89-103
Dagne, E., (1996b). NAPRECA and its Role in the Dissemination of Information on Natural Products Research in Africa. In "Bridge Builders". National Academy Press, Washington D.C.. pp. 217-231
Duddeck, H., Yenesew, A. and Dagne, E. (1987). Isoflavonoids from Taverniera abyssinica. Bulletin of the Chemical Society of Ethiopia 1:36-41
Noamesi, B.K., Bogale, M. and Dagne, E. (1990). Intestinal smooth muscle spasmolytic actions of the aqueous extract of the roots of Taverniera abyssinica. Journal of Ethnopharmacology.
OAU-STRC (1985). African Pharmacopoeia. OAU - STRC, Lagos.
Rajaonarivony, J.I.M. (1996). The Implementation of a Governmental Policy in Natural Products Research and Development in Madagascar. In "Science and Africa: Utilizing Africa's Genetic Affluence through Natural Products Research and Development." AAAS Symposium, Washington D.C. pp83-98.
Taniguchi, M., Kataoka, T. Suzuki, H., Uramoto, M. Ando, M., Arao, K.. Magae, J., Nishmura, T., Otake, N. and Nagai, K. (1995). Costunolide and dehydrocostus lactone as inhibitors of killing function of cytotoxic Tlymphocytes. Bioscience, Biotechnology and Biochemistry. 59:2064-2067.
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