Year

2020

Degree Name

Doctor of Philosophy

Department

School of Chemistry and Molecular Bioscience

Abstract

The medicinal plants, Vitellaria paradoxa, Neorautanenia mitis, Hydnora abyssinica and Senna surattensis, are used by Nigerian traditional medical practioners (TMP) to treat the symptoms of diarrhea in animals and humans. This study aims to validate claims of the traditional use of these plants in the treatment of diarrhea and provide a scientific basis for further studies. The crude aqueous extracts of these plants were evaluated for their antidiarrheal activity in a castor oil (CO) induced diarrhea model and in the gastrointestinal transit of charcoal model in albino rats, their acute toxicities were also determined in albino rats. There was no mortality recorded in the rats at the dose 2000 mg/kg, therefore the LD₅₀ in rats was considered higher than 2000 mg/kg for all the extracts. In the CO induced diarrhea model, the highest percentage inhibition of defecation was observed in the test groups treated with the extracts of H. abyssinica (82%) followed by S. surattensis (81%), N. mitis (66%), and V. paradoxa (32%). The H. abyssinica extract also decreased the intestinal transit of charcoal meal significantly compared to the other extracts. The antidiarrheal activities of the crude extracts give credence to their traditional use. Further studies on N. mitis led to the isolation of one new and 19 known natural product compounds, eight of these were isolated for the first time from N. mitis. These compounds were screened for CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) inhibitory activity and four of these compounds inhibited cAMP-induced Cl− secretion across T84 cell monolayers; dolineone (10), neodulin (2), pachyrrhizine (6) and neotenone (7) with IC₅₀ values of 0.81, 2.42, 2.87 and 4.66 µM, respectively. Compound 7 also showed reduction in defecation by 65% in CO induced diarrhea, while compound 2 showed pronounced relaxation of jejunum contraction in a concentration dependent manner, giving a complete relaxation at 194.7 µM in the isolated rabbit jejunum model.

FoR codes (2008)

0301 ANALYTICAL CHEMISTRY, 0304 MEDICINAL AND BIOMOLECULAR CHEMISTRY, 0305 ORGANIC CHEMISTRY, 1104 COMPLEMENTARY AND ALTERNATIVE MEDICINE

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Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.