Investigation of the in vitro and in vivo effects of some herbal preparations on risk factors for calcium oxalate kidney stone disease

Doctoral Thesis


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University of Cape Town

Several herbal preparations (Folium pyrrosiae , Desmodium styracifolium, Hylocereus trigonus, Phyllanthus niruri, Orthosiphon stamineus and Cystone®) were investigated as potential therapeutic and prophylactic agents for kidney stone disease. These studies were executed in the context of the existence of a virtually stone-free (black) and a stone-prone (white) population group in South Africa, with a view of establishing whether their respective renal responses are different. The independent in vitro effects of six plant extracts were tested on the crystallization characteristics of calcium oxalate (CaOx), the predominant stone-forming salt in urine. These investigations were performed in synthetic urine and real urine collected from healthy black and white South African males and the following parameters were assessed: urine composition; CaOx metastable limit; particle size-volume distribution; 14 [C]-oxalate deposition kinetics; CaOx crystal nucleation, aggregation and growth kinetics; examination of crystalluria by scanning electron microscopy and calculation of various physicochemical risk indices (Bonn Risk Index, Tiselius Risk Index and the relative urinary supersaturation of several stone-forming salts). All plant extracts inhibited one or more of the crystallization processes. Furthermore, crystal-cell binding, another risk factor for stone formation, was investigated in the presence of plant extracts. Madin-Darby canine kidney (MDCK)-I cells were used for this experiment. Crystals (inorganic and urinary) were bound to cells incubated in both aqueous media and real urine. Results showed that plant extracts reduced crystal binding under some but not all conditions. One of the extracts (Folium pyrrosiae) was administered to healthy South African black (n=9) and white (n=9) males in a double-blind placebo-controlled study. No significant effects on urine chemistry were found and there were no significant differences between the race groups post- treatment. Compounds from this herb were isolated and purified by the use of sequential liquid-liquid extractions and gel-permeation chromatography. A novel compound, 5 - (3 -(5,5 -dihydroxy-3- oxopentyl)phenoxy)-2-hydroxy-5H-indene-6-carboxylic acid , was identified using mass spectrometry and nuclear magnetic resonance imaging spectroscopy. The findings in this thesis have contributed to the body of knowledge about kidney stone disease. It has been demonstrated that some herbal preparations may be potentially useful in treating and managing this disease, but further clinical testing is required prior to the implementation of such an approach.

Includes bibliographical references.