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Keywords: Applied Sciences
Medicine & health
Pharmaceutical sciences
Issue Date: 2011
Publisher: University of Peshawar
Abstract: This PhD thesis envisages the phytochemical and pharmacological studies of an important member of Rhamnaceae family, Zizyphus oxyphylla Edgew. The main objective behind this investigation was to authenticate the folkloric history of this plant. Some of the folkloric uses of genus Zizyphus from the available literature include antidiabetic, hepatic protective, antioxidant, and antiulcerinic, antibacterial and anticancer while specifically Zizyphus oxyphylla is famous for its analgesic, antipyretic and hepatic protective uses. Fractions of stem, leaves and roots of Z. oxyphylla were screened for phytochemical constituents while fractions of stem and leaves were screened for pharmacological activities. This scientific pursuit resulted in some significant findings. The phytochemical studies on Z. oxyphylla resulted in isolation and structural elucidation of three new compounds. Two of the new compounds were cyclopeptide alkaloids named Oxyphylline B (1) and Oxyphylline C (2) while the third new compound was a flavone i.e. (+)-R, S Maackiain (3). Apart from these new compounds four other compounds Oxyphylline D (4), Nummularine-C (5), Nummularine-R (6), -Sitosterol (7) and Stigmasterol 3- O- -glucosides (8) were also isolated. Amongst these known compounds only Nummularine-R (6) was previously isolated from Z. oxyphylla while other known compounds were isolated for the first time from this plant and thus new source. Oxyphylline B (1), Oxyphylline C (2) and Nummularine-R (6) were isolated from the chloroform fraction of stem of Z. oxyphylla. From the dichloromethane fraction of roots Oxyphylline D (4) and Nummularine-C (5) were isolated while (+)-R, S Maackiain (3), -Sitosterol (7) and Stigmasterol 3- O- -glucoside (8) were isolated from the ethyl acetate fraction of leaves of Z. oxyphylla. Stem and leaves oils sub fractions, when analyzed by GC-MS, yielded fatty acids, lipids, long chain hydrocarbons and long chain ketones. Some major compounds which were yielded in high percentage were Heptacosane (10.0782 % in sample WO3), Tetracosane acid, methyl ester (9.2234 % in sample WO2), Dotriacontane, 1-Hexacosene and 1-Eicosene (6.4403, 6.6830 and 6.1095 respectively in sample WO5), 11decyl Tetracosane, (4.2749 % in sample WO1), Azafirin (4.4609 % in sample WO1) and 9-octyl Hexacosane, (3.7489 % in sample WO1). While other known compounds below were 3 % concentrations. Few of the peaks in gas chromatogram and their respective mass spectral data remained unidentified. As regards to pharmacological studies, some interesting and significant findings were obtained. Crude extracts, fraction and some of the isolated compounds were investigated for antibacterial, antifungal, toxicity tests (Brine shrimp bioassay, lemna bioassay, insecticidal), in vitro anti-inflammatory activity and enzyme inhibition bioassays including urease and carbonic anhydrase inhibition bioassays. Only ethyl acetate fraction of leaves showed moderate antibacterial activity. Crude extract and n-hexane fraction of leaves and only n- hexane fraction of stem exhibited 35 % inhibition of fungal growth. Maximum phytotoxic activity was revealed by both stem and leaves at the highest concentration used. Crude extract of leaves gave the highest inhibition (90 %) while chloroform was the most active fraction of stem of Z. oxyphylla. Neither of the extracts and subsequent fractions from stem or leaves were able to produce an impression as active cytotoxic agent. n-hexane and ethyl acetate fraction of leaves exhibited 40 % mortality against Callosobruchus analis. Two fractions of leaves (chloroform and n-hexane) gave excellent anti inflammatory activity when screened for in vitro anti- inflammatory activity. Polar fractions of stem showed the maximum urease inhibitory activity. Ethyl acetate fraction of the stem gave maximum reading of 86.7 % ± 0.03, while leaves showed low urease inhibitory activity. Stem and leaves of Z. oxyphylla exhibited low to moderate carbonic anhydrase activity. Oxyphylline B (1) showed comparatively better antibacterial activities against Escherichia coli and Pseudomonas aeruginosa (MIC: 0.1 mg/mL). Oxyphylline C (2) showed a lower antibacterial activity as compared to Oxyphylline B. Oxyphylline D (3) showed its highest antibacterial activity against E. coli and it lowest antibacterial activity against Shigella flexenari. Nummularine-C (5) and Nummularine-R (6) when compared we found that Nummularine-C was more active than Nummularine-R in many cases. Oxyphylline B (1) showed low activity against Candida albicans. While in the case of Oxyphylline C (2) it was found that it was moderately active against three fungal strains i.e. C. albicans, Micropspoum canis and Fusarium solani. Nummularine-R (6) and Oxyphylline B (1) showed low inhibition of Jake bean urease. Both of them gave readings of 35.73 and 34.24 % inhibition. Maximum urease inhibitory activity was shown by Oxyphylline D (3). It inhibited the urease enzyme by 58.21 %. When IC50 ± SEM value was calculated it came out to be 420.11 ± 1.22 μM. New compounds
Appears in Collections:PhD Thesis of All Public / Private Sector Universities / DAIs.

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