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Abstract
The contributions of natural products research to the quality of life are continually reinforced with the discovery of new and more effective drugs from natural origin. The broad aim of this thesis was to conduct a chemical and biological investigation of the plant Achillea fragrantissima, family Asteraceae.
The choice of the plant was based on its folkloric use among Egyptian Bedouins for the management of diabetes mellitus. Since there were no pharmacological studies linking A fragrantissima to diabetes, this thesis was warranted. Additional aims include subjecting the extracts, chromatographic fractions and pure compounds to other available bioassays to evaluate the potential use of this plant (or its constituents) in the treatment and/or prevention of regional diseases.
The initial phases of this work focused on evaluation of both the invivo and invitro antidiabetic activity of different Achillea fragrantissima extracts. The invivo assay revealed that both the chloroform extract and the crude polysaccharide fraction possess significant activity (reduce blood glucose level by 40%). Hexane extract, ethanol extract and water infusion reduced blood glucose levels by 36%, 34% and 22% respectively. A water extract prepared as a decoction reduced blood glucose by approximately 10% indicating the possible presences of antidiabetic compounds which may have decomposed or denaturated in the boiling process. In the invitro antidiabetic assay, only chloroformic extract and alcoholic extract showed α-amylase inhibition activity. The second phase in the work focused on large scale extraction of the plant with different solvents, followed by phytochemical screening to determine the chemical nature of its constituents. Investigation of the lipid content of the plant was performed through gas chromatography carried of the saponified and unsaponified matters of the hexane extract. The major terpenoidal compound was 2, 6 dimethyl 3, 7 octadiene 3, 6 diol (linalool derivative) with a percentage of 14.38% and the major hydrocarbon detected was docosane (4%). Arachidonic acid was the major unsaturated fatty acid with a percentage of 43%. This poly unsaturated fatty acid is known to stimulate insulin secretion from the pancreatic β cells, and this may explain the antidiabetic activity of the hexane extract. Palmetic acid was the major saturated fatty acid (6.3%).
The third phase of the work focused on the isolation and purification of seven compounds using different chromatographic methods.
The first compound (1) is a diacyl glycerol derivative of palmetic and linoleic acid. This is the first report of this compound in genus Achillea. The second compound (2) is a new sesquiterpene lactone of pseudoguaianolide type: 1 α, 4 α endoperoxy pseudo guaia -7(11), 10(14) diene 6 β, 12-olide. Compound (3) is eupatilin 7-methyl ether and was isolated for the first time from this species. Compound (4) is cirsimaritin flavone which was reported before from this plant. Compound (5) is β-sitosterol glucoside, beside two glycosyl flavones compounds (6) and (7). Identification of the isolated compounds was carried out by a variety spectroscopic methods including 1and 2 D NMR, UV, and Mass spectroscopy. Identification of the sugar monomers resulted from acid hydrolysis of the crude polysaccharide was also performed.
The last target of this thesis was to study other biological activities of the isolated compounds. The bioassays proved that compound 3 had antimalarial and antilieshmanial activities. The results of the antioxidant assay revealed that, compounds 2 and 4 possess significant antioxidant activity and compounds 1 and 3 showed moderate activity, while β-sitosterol glucoside is inactive.
This thesis has resulted in the isolation and structure elucidation of seven compounds, one of which has never been reported before. It also confirmed and further enhanced our understanding of the antidiabetic activity of Achillea and indicated promise for new biological activities and medicinal potential for this plant in treating malaria, lieshmania and for protection against tissue damage caused by oxidants.
Key Words: Achillea fragrantissima- antidiabetic-sesquiterpene lactone-flavones-, antimalarial and antilieshmanial activities- antioxidant activity.