Ethnopharmacology, phytochemistry and biological activities of malian medicinal plants

Abstract

This thesis presents the results of ethnopharmacological, phytochemical and biological activities investigations on Opilia celtidifolia (Guill. & Perr.) Endl. ex Walp (Opiliaceae), Cola cordifolia(Cav.) R. Br. (Sterculiaceae), and Erythrina senegalensis DC (Fabaceae), three plants used in traditional medicine in Mali to cure various types of diseases. The first part of this thesis deals with the results of ethnopharmacological surveys performed to identify the traditional uses of these plants. These studies covered different areas of Mali (Siby Dioila, Kolokani, Dogonland, and Koutiala) and their results showed extended uses of the plants. O. celtidifolia was mostly identified by traditional healers as an anti malaria, appetizer, and anti dermatitis plant and C. cordifolia was reported to cure gastritis, skin inflammation, wounds, malaria, high blood pressure, overweight and other diseases as well. The ethnopharmacological information of E. senegalensis was related mostly to amenorrhoea, bilharzias and other types of infections, malaria and jaundice. The fidelity level among traditional healers from the same area about the most reported diseases was calculated. A high healer agreement (75%) was found about the use of O. celtidifolia against dermatitis in Siby, against malaria in Dioila (61%), and abdominal pain (54%) in the same area. The use of E. senegalensis against amenorrhoea meets 21% of agreement between Dioila and Kolokani.The second part of this thesis presents the results of structural and immunological properties investigations of pectic polysaccharide fractions isolated from the water 50 ˚C extract of O.celtidifolia and C. cordifolia. These plants were previously reported to be used to treat internal and external chronic wounds. It is known from the literature that the plants which are used against wounds and other immune related diseases in traditional medicine are likely to contain immunomodulatory compounds, and polysaccharides are largely reported to be responsible of these activities. Two acidic polysaccharide fractions were isolated from the leaves extract of O. celtidifolia,Oc50A1 and Oc50A2. They showed, strong complement fixing ability, the ICH50 values were 0.5 and 0.9 g/ml respectively; nitric oxide release ability from activated macrophages, a concentration of 100 g/ml induced the release of about 7.3 M of NO. The fractions induced 14 and 24% respectively of proliferation of T cells at 50 g/ml and moderate B cell activation property at 100 g/ml as well. Analysis of the monosaccharide composition of Oc50A1 and Oc50A2 showed the presence of arabinose (26.7 and 13.2%), galactose (31.5 and 28%) and galacturonic acid (5.3 and 7.8%) respectively. The Yariv test confirmed the presence of arabinogalactan type II in both fractions. Structural analyses did also show the presence of terminal and 1-4 linked galacturonic acid and terminal and 1-2 linked rhamnose. Endo-polygalacturonanase treatment was performed to isolate the heavily substituted parts of the polysaccharides. These parts contained the same monosaccharides in similar proportion, and showed stronger dose dependent complement fixing activity and also stimulated macrophages to release nitrite oxide. A pectic polysaccharide Cc50-1 with a molecular weight between 1000 and 2000 kDa was isolated from C. cordifolia. Monosaccharide composition and linkages analysis showed the presence of unusual type of monomers. 20% of terminally and 3-linked 2-O-methyl galactose, 18% of terminally linked 4-O-methyl glucuronic acid and 2% of 2-O-methyl fucose were identified. These monomers seem to be linked to a RGI like backbone composed of 20% of 2,3- and 2,4-linked rhamnose almost equal amount, which alternate with 24% of 4-linked galacturonic acid some of which also carry side chains. This polysaccharide showed low complement fixing ability with an ICH50 value of 480 g/ml. Viscosity measurement gave a Huggins constant value of K´=1.2 which indicated the presence of aggregated particles when Cc50-1 is dissolved in water based solvents.In the last part of the thesis, results of phytochemical and biological investigations on low molecular weight compounds isolated from E. senegalensis are presented. A new pterocarpan named Erybraedin F and six known ones, erybraedin A, C, D, eryvarin K, phaseollin and shinpterocarpin and a flavone, carpachromene were isolated from the dichloromethane extracts of the root and stem bark. The pterocarpans showed 15-lipoxygenase enzyme inhibition activity. The IC50 values ranged between 32 and 82 M. Erybraedin D (IC50 < 32) was stronger enzyme inhibitor than quercetin (IC50 = 42 M). Erybraedin A, D, C and eryvarin K also showed positive inhibition results on Staphylococcus aureus. The antimicrobial activity of the compounds is in good agreement with literature data. These compounds although reported before in the genus Erythrina are for the first time here reported in the species E. senegalensis and the first time reported to have 15-LO inhibition activity.