Plants are a biologically and chemically diverse resource ,vith estimates of 250,000 - 500,000 species occurring on our planet (Cox and Balick, 1994; Borris, 1996). To date, less than 10% of the total plant kingdom have been examined
scientifically for their potential in medicine (The Lancet, 1994).
The use of medicinal plants, a major component of Indigenous/traditional med1c1ne, for treating diseases can be traced back to written documents of the early civilizations 1n China and India as far back as 168 BC (Hamburger and Hostettman. 1991 The Lancet-edilorial-1994; Holland, 1994). Although modern medicine has lessened the dependence on medicinal plants as the sole source of
drugs, nonetheless. the use of plants is still the almost exclusive source or drugs for over 80% of the world's population which utilise plant-based medicines for primary health care (Hamburger and Hostettmann, 1991, Phillipson and Wright, 1991, Ph1ll1pson 1994 Borns, 1996) The greater proportion of the world popota11on that still use exlracls from plants to treat wide ranging diseases can
bo found 1n dovclop1ng countries (Cox and Balick, 1994). In lnduslriollsed countnos, �lsnccs derived from higher plants constitute about 25% of
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prescribed medicines (Farnsworth and Bingel, 1977; Principe, 1989; The Lancet
editorial-1994). Furthermore, the use of plants in the form of phytomedicines is increasingly becoming widespread in some developed countries of Europe like Germany, France, The Netherlands, and Sweden (Bohlin, 1993; King, et al.,
1996)
Interest in natural products research particularly that based on medicinal plant has been a cyclical phenomenon over the years. An early scientific approach 10\vards the treasure of traditional medicine In Europe was documented ,n the late 18th century. In 1785, the British physician William Wilhering reported that ingestion of dried leaves of the Foxglove (Digitalis purpurea) eased dropsy, nowadays known to be caused by heart failure (Cox and Balick, 1994) His ong1nal source of information \Vas an old woman knO\vn for her great herbal knowledge. Oig1lalis 1nciud1ng its active glycosides, and the pure compounds d1goxin and dig1loxin Isolated from Iha plant were later made available for many cardiac pahents. This event represents one way by which the medical potential
of the plant kingdom together with its diversity or chemical resources can be used for I.ho benef i t of mank ind. Following the lsolotlon or dlg1talls compounds, many important substances like morphine, quinine, tubocurarine, pllocarpine, codeine, vinblastino, v1nCt1slfne (oil of which have been known for yoars) havo boon
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prescribed medicines (Farnsworth and B1ngel, 1977, Principe, 1989; The Lancet
editorial-1994) Furthermore, the use of plants in the form of phytomedicines is increasingly becoming widespread 1n some developed countries of Europe like Germany, France, The Netherlands, and Sweden (Bohlin, 1993; King, et al.,
1996)
Interest in natural products research particularly that based on medicinal plant has been a cyclical phenomenon over the years. An early scientific approach towards the treasure of traditional medicine in Europe was documented 1n the late 18th century In 1785, the British physician William Withering reported that ingestion or dried leaves of the Foxglove (Dig/la/is purpurea) eased dropsy, nov,adays known to be caused by heart failure (Cox and Ballek, 1994). His original source of information was an old woman known ror her great herbal knowledge Dig1tahs 1nclud1ng its active glycosldes, and the pure compounds
d1gox1n and d1g1toxin isolated rrom the plant were later made available for many cardiac patients This event represents one way by ,vhich the medical potential
of the plant kingdom together with its diversity or chemical resources can be used •
for the benefit of mankind Following the Isolation or digitalis compounds, many irn;,oruint &ubstancos hke morphine, quinine, tubocurarine, pilocarp1ne, codeine,
vinblastino, v1ncns1tno (all of which have been known lor years) have been
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discovered through scientific investigahon of folklore claims. Some of them, for example, digitalis cardiac glycosides, are stlll the drug of choice ,n their
respective areas of therapy (The Lancet, 1994, Cox and Balick, 1994).
Around the 1950s, interest ,n medicinal plant consumption and research
waned after storming advances In synthetic chemistry and molecular biology promised to supply new means for designing drugs in the laboratory
Consequently most pharmaceullcal firms abandoned the search for therapeutic compounds ,n higher plants (Cox and Balick, 1994, Borns, 1996; Turner, 1996)
However, since 1970 there has been a resurgence of interest in medicinal plant research and plant-<lerived products. Ecological a\vareness and an Increased demand for non-classical therapies have been advanced as reasons for the revival of interest (Hamburger and Hostenmann. 1991, Turner, 1996, Borris, 1996) Another maJor reason is the undisputed cllnlcal efficacy of several plant denved drugs An example 1s the use of artemisinlne, derived from a Chinese medicinal plant Artem1s1a annua L(Qinghao) in severe malaria for which chloroqu,ne may not be helpful (UNDP/World Bank/WHO, 1991) Other examples of ciin1cal!y important plant-<lerived drugs are taxtds (from Taxus UNIVERSITY OF IBADAN LIBRARY
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The awareness that compounds with less direct therapeutic potential may offer new molecular templates for the design of more effective drugs has also
contributed lo the renaissance of interest in medicinal plant research (King el al.,
1996: Turner, 1996; Borris, 1996).
Bearing in mind the rene,ved interest in medicinal plant research, it has been reported that the alarmingly rapid rate or species extinction which is currently occurring, due in part to habitat destruction calls for certain urgency to the quest for plant-derived drugs (King et al., 1996, Boris, 1996, Turner, 1996).
Moreover since the system of Indigenous medicine are based on a vast amount of empincal knowledge about the treatment or diseases, it 1s recognised that the
gradual ·ext1nclion· or the trad1t1onal medicine prachlloners. together with their wealth of knowledge about folk medicine ,vould mean a big loss or valuable and
vital e1hnomed1cal 1nrormation
The studies carried out 1n this thesis are in recognition or the resurgence of interest 1n med1c1nal plant research II is behaved that a concerted effort using the approach of elhnobotany/ethnopharmacognosy and elhnopharmacology may lead to the d,scovery of yet more novel compounds which may be used directly as tno(Bpeot1c agent, oc offer medicinal chemists leads In lhe design of more
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effective therapeutic agents This prompted investigation of some of the ethnomedical uses of Alston,a boonei de wild (Apocynaceae)in this study
A boonei de wild (Apocynaceae), the medicinal plant inveshgaled 1n this thesis, ,s used 1n indigenous medicine ,n the continents of Alrica and Asia to treat a number of diseases including malaria, fever, rheumatoid arthritis, dysentery, insomnia. abdominal discomfort, hypertension, and painlul m1cturihon (Burkhil, 1935 Perry and Metzger, 1980, Ojewole, 1984, Asuzu and Anaga, 1991) The plant extract has also been given after child birth lo help the delivery or the placenta (Dalziel, 1937, Irvine, 1961). The plant 1s widely grown in West Africa In Nigeria 11 1s mainly used 1n trad11ional medicine to treat malana, raver and
rheumatic pa,ns (Ojewole, 1984), In Ghana, 1t Is used primarily to lreat rheumatoid arthritis (Kwe1fio-Oka1 1 1991(a); 1991(b)
The use or the plant to treat malaria by far outweighs other uses and 11 is not surpr1s1ng that sc1ent1f1c investigation of the ethnopharmacology or lhe plant have IOOJssed more on the antimalarial properly than on other biolog,cal effects Howe,er the many studies that have so far been earned out have failed to identify a prom1s1ng anhmatonal compound which can e1lher be used directly as a thefapeut c �nt or as a template ror the synthesis or a more etfecllve 00fflP(UlCI Fur1hermore there exists considerable controversies on the efficacy
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of extracts of Alston,a species or their constituents 1n malaria (Wright, et al, 1993) Studies ,n v,tro using several compounds isolated from the plant have not proven it to be a prom1s1ng ethnomedlcine from which an effective antimalarial drug can be developed However, the results lend some support to the use of Alstonia species 1n trad1honal medicine (Phillipson et al, 1993) It must be pointed out however that many of the chemical constituents from the plant have not been isolated following activity-guided isolation procedure. Therefore ll Is probable that the most active antimalarial conshtuent(s) of the plant has not been isolated (might have been missed). Furthermore, it has been reported thal nothing appears to be kno\vn about the ,n vivo achv1hes of Alstonia species (Ph1lhpson el al, 1993) This underscores a need for ,n vivo st udies. This is more
pertinent 1f 11 1s assumed that pro-drugs are the active constituents of Als/onia species
In this thesis, two elhnomed1cal uses of the plant, antimalarial and ,mmuoomodulatory (antunOammatory) were investigated The choice of these
diseases 1s based on the prevalent use of the plant extract 1n the two conditions
1t1 Nra Ant,matarial acllv1ty was 1nves11gated in 111vo using drug-sensitive end resistonl-<odont malaria poros,tos AntlinOammotoryllmmunomodulotory activity wa, 1nvoi'.Jgo'ed 1n VI ,o using zymosan-,nduced footpad Inflammatory modal In
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resistant-rodent malaria parasites Ant1innammatory/immunomodulatory activity was invesltgated 1n vivo using zymosan-1nduced footpad innammatory model in
mice and 1n vitro on complement system and polymorphonuclear (PMN) leukocytes The choice of the two immunological parameters is based on their close assoc1allon with acute inflammatory responses and the impllcalion of
complement 1n the pathogenesis of a variety of rheumatic disorders (Benencia et
al, 1994, Morgan 1990; Pamham et al, 1984).
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Abstract Algebra: Theory and Applications
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