The use of the oral cavity membranes as sites of drug administration has been a topic of increasing interest for the past decade. The buccal route, in particular, offers several advantages over the per oral route and may prove to be a viable alternative to other routes for drug delivery, as it bypasses hepatic first pass metabolism, thereby improving the systemic bioavailability of the administered drug. A controlled drug release formulation may further enhance the therapeutic efficacy of a buccal drug delivery system. Propranolol HCI (PHCI), a non-selective p-blocker, primarily advocated in the treatment of hypertension, has a short half-life (3 - 6 hours) and is also subjected to extensive hepatic first-pass metabolism following oral administration, resulting in a low oral bioavailability, therefore rendering it an ideal candidate for buccal drug delivery. For optimal controlled release and mucoadhesivity of a buccal delivery system containing PHCI, the blending of polymers and drug of opposing solubilities may be required for the formation of monolayered films. The aim of this study was therefore to formulate and characterise multipolymeric monolayered mucoadhesive films containing drug and polymer/s of opposing solubilities for the buccal delivery of PHCI. First, preparation parameters for the formation of monolayered multipolymeric films (MMFs) and homopolymeric PHCI films comprising drug and polymer/s of opposing solubilities, i.e. Chitosan (CHT) and Poly(D,L-lactide-co-glycolide) (PLGA) by an emulsification/casting/solvent evaporation method were investigated. MMFs could be prepared at all homogenisation speeds (6000, 9000, 12000, 15000 rpm) and times (1, 5, 15, 25 minutes). The films showed micromatrices embedded in the film matrix due to the inclusion of the PLGA polymer. Increased homogenisation speed and time resulted in a reduction in the size of the micromatrices. Phase separation occurred at temperatures below 20 °C. Emulsifiers employed in the study (Poly(vinylalcohol) (PVA) and Tween 80®) adversely affected the morphology and appearance of the film and were therefore not considered feasible for inclusion in the formulation. The preparation parameters identified for emulsification without phase separation and the subsequent generation of monolayered films, without phase separation during solvent evaporation and drying, were emulsification at 20 °C and homogenisation at 9500 rpm for 15 minutes. It was discovered through preliminary investigations and a comprehensive literature search that the conventional film casting method of film preparation suffered from poor drug content uniformity. To address this problem of non-uniformity, a specially designed silicone-molded tray (SMT) for film casting was prepared and evaluated in terms of enhancing drug content uniformity. These investigations confirmed that the SMT with teflon-coated perspex inserts provided a reproducible method for the preparation of both homopolymeric and multipolymeric (including drug and polymers of similar and opposing solubilities) films that met drug content uniformity requirements (assay values were within 92-107.5%) and also reduced the variability in mucoadhesivity (p=0.2922), drug release [fi values = 92.76, 90.99 and 86.06) and film thickness for all three trays. The final phase of this study involved the identification of a suitable polymeric blend for the preparation of MMFs comprising hydrophilic and hydrophobic polymers for the controlled buccal delivery of PHCI and subsequent characterisation of these films in terms of their physicochemical/mechanical properties. Initial investigations of different polymers for the formation of homopolymeric films showed that the combination of drug and polymer/s of opposing ionic states was not possible due to complexation. PHCI film formation as homopolymeric films was achievable with hydrophilic polymers, Hydroxypropylmethylcellulose (HPMC) and CHT, and hydrophobic polymers, Ethylcellulose (EC) and Eudragit® RSI00 (EUD100). It was also found that combining PHCI, a hydrophilic drug, with a hydrophilic polymer (CHT or HPMC) failed to retard drug release (> 80% at 1 hour), whilst the release of PHCI from a homopolymeric film comprising a hydrophobic polymer (EC or EUD100) was retarded. A PHCIiEUDlOO (1:10) film provided controlled release but was too retarded (< 67% at 8 hours) for the purposes of this study. Hence, the polymeric content of the formulation was altered by the addition of a hydrophilic polymer CHT, to obtain the desired controlled release profile. A PHCI:EUD100:CHT (1:10:0.5) polymeric blend (MMF) was found to be suitable for the controlled release of PHCI and was reproducible in terms of drug content uniformity (p=0.1964), drug release [h values = 83.18; 82.03 and 71.19) and mucoadhesivity (p=0.9971). Drug release followed Higuchi's square-root model (r2=0.9426). Scanning electron microscopy revealed that the addition of CHT to the PHCI:EUD100 (1:10) film formulation rendered it more textured, which contributed to the faster drug release observed with the PHCI:EUD100:CHT (1:10:0.5) MMF. Swelling and erosion studies indicated that maximal swelling of the films occurred after 1 hour and 28.26% of the film eroded during the 8 hour test period. The system also demonstrated acceptable mucoadhesivity and mechanical properties. The surface pH of the films also remained constant at neutral pH throughout the study. The data obtained in this study confirmed the potential of this multipolymeric monolayered film system as a promising candidate for the controlled buccal delivery of PHCI. Key words: Films; Buccal; Multipolymeric; Mucoadhesive; Controlled drug release; Propranolol HCI / Thesis (M. Med. Sc.) - University of KwaZulu-Natal, 2007.

Practicing clinical veterinarians in large companion animal practices are often faced with the phenomena of epileptic seizures which occur commonly in dogs. The high incidence of non-responsive cases is often frustrating, and the literature offers incomplete, conflicting and often inaccurate information. The concept of therapeutic anti-epileptic drug concentration monitoring, as applied in man as an aid to treatment, appears attractive in order to provide an improved service to the patient and client. An investigation into the pharmacokinetics of phenobarbitone, particularly at steady state, became necessary in order to interpret the application of drug serum concentration monitoring. The trend of veterinarians to extrapolate human kinetics to dogs is common and unsound. This study was an attempt to identify the similarities and dissimilarities between the pharmacokinetics of dogs and humans. No literature was available, both for man or animal, on the effect of food on the absorption of phenobarbitone. As dog owners frequently have to administer oral medication in food, this was an important factor to examine. The kinetics of the drug was determined in a group of epileptic dogs in order to provide a possible base-line therapeutic regime on commencement of treatment, and the practical application of therapeutic drug monitoring in order to individualize and improve response to treatment was explored. / Thesis (M.Sc.)-University of Durban-Westville, 1990.

Schistosomiasis is an important public health issue for rural communities located near,or around slow moving water bodies in the tropical and subtropical areas. Successful control of the disease involves multifaceted approaches, which include snail control, environmental sanitation, health education and chemotherapy. Although snail control might be an effective method of controlling schistosomiasis, there has been a general lack of control initiatives, largely due to the cost of available molluscicides. Plants offer a wide array of compounds which, on extraction, may show molluscicidal activity. If molluscicidal compounds that occur in indigenous plants can be extracted using local labour and simple technology, then there should be culturally acceptable and inexpensive molluscicides. The aim of this study was, therefore, to screen some Zulu medicinal plants for molluscicidal activity. We have also attempted to isolate the active chemical compounds from such plants. Aqueous and methanolic crude extracts of ten (10) Zulu medicinal plants, used for different medicinal and domestic purposes, were screened for molluscicidal activity on Biomphalaria pfeifferi and Bulinus africanas snails reared in the laboratory during the time of bioassay. Bayluscide® (niclosamide) was used as a positive control for comparison, while de-chlorinated tap water was used as the negative control. Six of the plants were not active against the snails. Extracts from four of the plants demonstrated weak to moderate molluscicidal activities. These plants are: (i) Sclerocarya birrea stembark, (ii) Psidium guajava (hybrid) leaves, (iii) Leonotis leonurus aerial parts and (iv) Ekerbegia capensis stem-bark. The LC50 values of the plant extracts were 78 ppm, 100 ppm, 398 ppm and 600 ppm respectively. Of the 4 plants that showed molluscicidal activity, S. birrea aqueous and methanol extracts were the most active against the snails, with LC50 values of 82 ppm and 78 ppm respectively. For the other plant extracts, only the methanolic extracts showed activity. Brine shrimp toxicity assay was performed with all the active extracts. Psidium guajava showed 10% survival of the shrimps at 1000 ppm, whereas no survival was observed for the other plant extracts at this concentration (1000 ppm). The results obtained in this study indicate that further studies have to be conducted, especially with S. birrea extracts, whose both aqueous and methanolic extracts showed significant activity against the snails. / Thesis (M.Med.Sc.)-University of Durban-Westville, 2002.

The development of a new class of antihistamines, the H2-receptor antagonists, introduced a new era in the treatment of peptic ulcer diseases. Cimetidine, the first clinically effective H2-blocker, was introduced in 1976. Recently ranitidine, a second member approved for clinical use, has been found to be as effective as cimetidine in the management of peptic ulcer diseases. Soon after the introduction of cimetidine several reports of loss of libido, impotence and gynaecomastia were described in male patients who were on normal or high therapeutic doses of cimetidine. A few unsubstantiated reports of loss of libido and gynaecomastia attributed to ranitidine therapy have also appeared in literature. This study was undertaken to examine in detail the effects of acute and subchronic treatment with cimetidine and ranitidine on mating behaviour in sexually active male rats. Motor activity counts were recorded immediately before sexual behaviour observations. The animals were tested on every third day and observations were terminated after the first intromission of the next series of copulations. In the single dose study, mating behaviour tests were commenced 2 hours after treatment; mating tests during the subchronic dose studies were done 4 to 7 hours after the 6hOO dose. The following measures were used in the analysis of data: mount latency, intromission latency, mount frequency, intromission frequency, ejaculation latency, and the postejaculatory intromission latency. At the termination of the subchronic dose studies blood samples were collected by cardiac puncture and the animals were subsequently autopsied. Cauda epididymal sperm counts and motility were determined, testes and accessory sex organs were weighed, and one testis was processed for histological examination. Cimetidine in the low dose, 128.6 mg/kg, significantly shortened the ejaculatory latency and to a lesser extent the postejaculatory intromission latency. At the higher dose, 257.1 mg/kg, cimetidine markedly prolonged the postejaculatory intromission latency and to a lesser extent increased the ejaculation latency. The inhibitory effect of cimetidine on copulatory behaviour at the higher dose level was accompanied by significant depression in motor activity. At the conclusion of the subchronic dose studies marked reductions in serum testosterone levels and decreased testes and accessory organ weights were observed in the cimetidine group. No significant changes in sperm counts were observed, although the sperm counts in the cimetidine group were lower than the control values. Histological examination of testes showed apparently normal spermatogenesis in all three treatment groups. However, in spite of the reduced testosterone levels and decreased testes and accessory sex organ weights in the cimetidine group, no impairment in mating behaviour was observed. In both the acute and the subchronic dose studies, similar to placebo, treatment with ranitidine showed no effect on mating behaviour. On final analysis of the results it is concluded that cimetidine, and not ranitidine, disrupts sexual behaviour in male rats. Furthermore, it is concluded that the effect of cimetidine on sexual behaviour is not related to H2-receptor blockade as equipotent doses of ranitidine did not produce similar effects. The mechanism of cimetidine-induced impairment of sexual performance in the male rat may possibly be attributed to some non-specific, direct or indirect action of cimetidine on some neurotransmitter system responsible for the control of sexual behaviour. It is further suggested that the effect may possibly be mediated by a blockade of central dopamine receptors. However, it must be stressed that further experimentation is necessary to elucidate the mechanism of action of cimetidine on sexual behaviour. / Thesis (M.Sc.)-University of Durban-Westville, 1985.

Escherichia coli, one of the most common pathogens causing urinary tract infections, has shown increased resistance to commonly used antibiotics. In this study we analyzed the β-lactamase profiles of 38 inhibitor-resistant E. coli isolates obtained from public hospitals at three different levels of healthcare in KwaZulu-Natal, selected on the basis of their resistance profiles to the three antibiotic/inhibitor combinations, viz., amoxicillin/clavulanate, ampicillin/ sulbactam and piperacillin/ tazobactam. The isolates were subjected to MIC determinations, IEF analysis, plasmid profile analysis, PCR of the different β-lactamase genes and sequencing thereof to detect the possible mechanism/s of resistance. A range of β-lactamases including two novel inhibitor-resistant TEM β-lactamases, TEM-145 and TEM-146 were detected in two isolates whilst a novel plasmid-mediated AmpC-type β-lactamase, CMY-20 was detected in three isolates. Other β-lactamases included OXA-1, TEM-55, SHV-2, CTX-M-l and TEM-1. Changes were detected in the chromosomal AmpC promoter/attenuator regions in one isolate. Diverse β-lactamase genes and plasmid profiles inferred extensive mobilization of β-lactamase genes causing the concern of limited therapeutic options in the face of increasing resistance. / Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2008.

The AIDS epidemic in Africa has reached dramatic proportions. Of the 42 million people infected with HIV worldwide, 30 million are in Africa. Current available therapies have begun to transform this fatal disease into a chronic condition but there are still major obstacles that have resulted in a great demand for new and better drugs. The aim of this study was to synthesize novel and effective HIV protease inhibitors. This work describes the first account of pentacycloundecane (PCU)-peptide and peptoid based protease inhibitors. These inhibitors are proposed to bind the wild type C-South African HIV protease (C-SA) catalytic site via the norstatine or dihydroxylethelene type functional group of the PCU. The desired compounds were synthesized by the coupling of the peptides and peptoids to the PCU cage which resulted in a series of promising and structurally diverse HIV-1 protease inhibitors. The inhibitors were characterized by Nuclear Magnetic Resonance (NMR) and evaluated against the wild type C-SA enzyme for its ability to inhibit 50 % of the enzyme’s activity (IC50). Two of the compounds reported herein, inhibited the enzyme activity at concentrations less than 80 nM. NMR investigations indicated that the activity was related to the chirality of the PCU moiety and its ability to induce conformations of the coupled peptide side chain. Employing the new Efficient Adiabatic Symmetrized Rotating Overhauser Effect Spectroscopy (EASY-ROESY) technique enabled us to obtain vital information about the 3D structure of these small linear peptides and peptoids in solution. This technique is the first example describing the successful through space correlations of such small peptides. Furthermore, docking and a combined quantum mechanics/molecular mechanics (QM/MM) molecular dynamics MD simulation at the AM1 semi empirical level mirrored the observed NMR results and the experimental IC50 activity profile of the considered inhibitors. The combination of these experimental and theoretical methods provided a powerful insight into the interaction mode of these cage peptide and peptoid inhibitors with the enzyme. / Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2011.

Plants have formed the foundation of traditional medicine systems throughout the world for thousands of years and continue to provide mankind with new remedies for various ailments. A large portion of the black South African population still depends on medicinal plants as primary health care due to its affordability, accessibility and cultural importance. These medicinal plants need to be investigated since new lead compounds are often found in nature. Homoisoflavanones isolated from South African and Indian plants were found to exhibit anti inflammatory activities although the mechanism of action has not yet been determined. A few reports on the anti fungal activities of these compounds were also found. Four new and three known homoisoflavanones of the 3-benzylidene-4-chromanone type were synthesized and tested for anti-inflammatory and antifungal activities. Two novel intermediates were also synthesised. Enantiomers of a homoisoflavanone of the 3-benzyl-4- chromanone types were also synthesized from the corresponding 3,5-dimethoxy phenol via 4- chromanone in six steps. This is the first report of the synthesis of an enantiomerically pure homoisoflavanone compound together with its opposite isomer. The enantiomers and racemate were tested for anti-inflammatory activity. All the synthesized homoisoflavanones were screened for cytotoxicity. The structures of these homoisoflavanones were elucidated by NMR spectroscopy along with HRMS data. The crystal structure of a homoisoflavanone with anti-inflammatory and antifungal activity is reported. The anti-inflammatory activity of the homoisoflavanones was determined in an acute croton oil-induced auricular dermatitis mouse model. The antifungal activity was performed in vitro against a Candida albicans strain. Compounds were tested for cytotoxicity against a Chinese Hamster Ovarian (CHO) cell line using the 3-(4,5-dimethylthiazol-2-yl)-3,5- diphenyltetrazoliumbromide (MTT) assay. In conclusion, the synthetic homoisoflavanones showed anti-inflammatory as well as antifungal activity. Some of the compounds showed anti-inflammatory activity comparable to that of the commercially available diclofenac. / Thesis (Ph.D.)-University of KwaZulu-Natal, Westville, 2011.

This research study undertook to investigate and evaluate for efficacy and safety, the herbal remedies used for treating Diabetes mellitus in northern KwaZulu-Natal. In addition, it sought to gain knowledge and better understanding of traditional healing systems and the medicinal use of the natural flora. During the process of assimilating the desired information, the epidemiological and socio-economic factors which determine the form of medicine chosen by rural people in the region, were quantified. Both aspects of explanatory studies i.e. experimental and observational were used. Firstly, to evaluate the safety of the two herbal remedies, laboratory animals were given an oral dose of the herbal medicine and observed for a period of 14 days. Efficacy was assessed by treating Streptozotocin-induced diabetic rats with the herbal remedies and comparing their effect on blood glucose with that of a conventional sulphonylurea. The second part of the study was observational and it involved monitoring human subjects (patients) for twelve months, who were already taking the herbal preparations (n=56) and comparing their prognoses with that of a group taking conventional medicine (n=97). A third group using both types of medicine (n=42) was included as control measure for a possible confounding factor. Main outcome measures; Both subjective and objective measures of the perceived health of the diabetic patients were measured, as well as the determinants of using traditional medicine versus conventional medicine. The battery of toxicity tests which utilises behavioural and functional observations of the laboratory animals, yielded no signs of toxicity or abnormal behaviour. The histopathological examination results of the sample organs from the treated rats also revealed no signs of abnormality that could be attributed to the herbal remedies tested. There was no sex variation recorded in the response. The first HP tested (HP-1) demonstrated minimal hypoglycaemic effect whereas HP-2 significantly lowered the blood glucose of the streptozotocin-induced diabetic rats by an average of 59%. This was comparable to the conventional medicine (Glibenclamide) used in the experiment. After 12 months of follow-up, 93 % of traditional medicine users (n=56) were convinced that their blood sugar was controlled because of the traditional remedy they were using. The proportion of diabetic cases who used conventional medicine were no better off than those who used traditional medicine or vice versa. Health status and the financial situation (income) of the respondents greatly influenced their choice for diabetic treatment. The herbal remedies that were investigated were non-toxic and safe for use and internal consumption. One preparation demonstrated a significant hypoglycaemic effect, which was comparable to the conventional allopathic medicine used in treating Diabetes mellitus. This study should serve as a springboard to encourage more pharmacological evaluation of herbal medicines. / Thesis (Ph.D.)-University of Durban-Westville, 1998.

The stereo-chemistry, structure activity relationships and the metabolism of the anorectic drug, diethylpropion hydrochloride, have been reviewed briefly, together with the analytical methods for the determination of this drug and its metabolites in biological fluids. In addition, the physico-chemical properties, mode of action, pharmacology and uses of the metabolites have been presented. A comprehensive review on general principles of salivary excretion of drugs and their therapeutic drug monitoring in saliva with relevant published data on saliva/plasma drug concentration relationships has been outlined. Sensitive and specific assay procedures, based on gas-liquid chromatography for the identification, separation and determination of diethylpropion and its two major metabolites i.e. ethylaminopropiophenone (11) and diethylnorpseudoephedrine (IV) in aqueous and biological fluids, have been developed. These methods were used to study the urinary excreUon as well as saliva and plasma levels of the two major metabolites and, where possible, the unchanged drug, in man. Sustained release pellets with diffusion rate-controlled membranes were employed to control the rate of input into the body by oral or rectal route of administration. Urinary excretion data and plasma levels of metabolites 11 and IV in volunteers, where the urine was controlled at an acidic pH, were used for the evaluation of the bioavailabilities of different dosage forms of diethylpropion hydrochloride. The concentrations of metabolites 11 and IV were also measured in saliva and in plasma after administration of the drug in different doses and dosage forms: relationships between saliva and plasma concentrations (S/P) and between urinary excretion rates and plasma concentrations (U/P) were developed for each of the two metabolites during plateau levels after oral administration of the sustained release pellets (Lot R 7773). The potential use of salivary excretion of the metabolites as an index to monitor their plasma levels and bioavailabilities, was examined. The distinct advantage of using a subdivided controlled release system (i. .e. sustained release pellets) to a single unit sustained release tablet (erosion-core type) in relation to influence of the physical presence of food on the rate and extent of absorption has been demons t rated . It was found that the route of administration (oral or rectal) did not significantly affect the bioavailability of the sustained release pellets. The study also involved the investigation of the release of the drug from the pellets. Because the release control step was diffusion, no significant influences on dissolution rates were observed with the use of different dissolution test models and agitation intensities. The influence of the concentration and composition (presence of cations viz. Na+ and K+ i~r anions viz . phosphate and borate) of the dissolution medium on the release of the drug from sustained release pellets, was also studied. Any potential changes in the dissolution pattern on storage of the pellets under different conditions (4°C, room temperature and 37°C) ovrr, a period of at least one year, were investigated. The in vitro and in vivo correlations of two lots of sustained release pellets, each exhibiting different dissolution profiles, and administered rectally and orally, were developed: the in vitro data on the free drug were related to the sum of the urinary excretion data of metabolites II and IV. An attempt to use an empirical approach to predict urinary excretion rate profiles of metabolite II after oral administration of the sustained release pellets, was promising; the calculated profiles were reasonably comparable with those of in vivo studies. However, the complete validity of such equations needs further investigations. / Thesis (Ph.D.)-University of Durban-Westville, 1984.

Background: Evidence from our laboratories indicates that triterpene constituents of Syzygium cordatum (Hochst.) [Myrtaceae] crude leaf extracts can be used to treat diabetes mellitus. For the plant derived triterpenes to have further potential in diabetes management, they should, however, additionally alleviate or prevent some of the complications of diabetes mellitus such as impaired kidney function and cardiovascular disorders. Accordingly, this study was designed to isolate the triterpene, oleanolic acid (OA) from S. cordatum leaves and evaluate its effects on blood glucose, renal function and blood pressure in streptozotocin (STZ)-induced diabetic rats. OA was studied because it is the major constituent of many African plant species used in traditional medicine. Materials and Methods S. cordatum crude leaf ethyl acetate solubles (EAS) were obtained after defatting the leaves with hexane followed by dichloromethane before maceration with ethyl acetate. Preliminary experiments indicated that EAS contained triterpenes with hypoglycaemic properties. Solvent extraction and fractionation of EAS yielded mixtures of oleanolic acid/ursolic acid (OA/UA) and methyl maslinate/methyl corosolate. Recrystallisation of the OA/UA mixture using ethanol yielded OA, the structure of which was confirmed by NMR spectroscopy ('H & 13C). Oral glucose tolerance test (OGTT) responses to various doses of OA (40, 80 and 120 mg/kg) were monitored in separate groups of non-diabetic and STZ-induced diabetic rats given a glucose load (0.86 g/kg, p.o.) after an 18-h fast. Rats treated with deionized water (3 ml/kg p.o.), or standard drugs, (insulin, 200 Hg/kg, s.c; metformin, 500 mg/kg, p.o. and glibenclamide, 500 f^g/kg, p.o.) acted as untreated and treated positive controls, respectively. To investigate the possible interaction between OA and standard drugs in lowering blood glucose, OGTT responses were studied in separate groups of animals simultaneously treated with OA at either 40 or 80 mg/kg and insulin (100 or 200 ug/kg, s.c), metformin, (250 or 500 mg/kg, p.o.) or glibenclamide (250 or 500 mg/kg, p.o.). Blood glucose was monitored at 15-min intervals for the first hour, and hourly thereafter for 3 h. Plasma insulin concentrations were measured in separate parallel groups of rats prepared as for OGTT studies to examine whether there was an association between OA treatment and pancreatic insulin secretion. Acute effects of OA on kidney function and mean arterial blood pressure (MAP) were investigated in anaesthetized rats challenged with hypotonic saline after a 3'/2-h equilibration for 4 h consisting of 1 h control, 1XA h treatment and 1 Vi h recovery periods. OA was added to the infusate during the treatment period. Short-term effects of OA were studied in individually-caged rats treated twice daily with OA (80 mg/kg, p.o.) for 5 weeks. Results OA decreased blood glucose concentrations of both non-diabetic and diabetic rats, as did some standard drugs except glibenclamide which did not exhibit any effects in STZ-induced diabetic animals. The blood glucose lowering effects were most potent in STZ-induced rats treated with combined OA and insulin by comparison with all other treatments. Short-term treatment of non-diabetic and STZ-induced diabetic rats with OA alone for 5 weeks decreased blood glucose concentrations, but the reduction in non-diabetic rats was to values that did not achieve statistical significance. Except for non-diabetic rats treated with insulin alone or in combination with OA, plasma insulin concentrations were not altered by treatment in non-diabetic and STZ-induced diabetic animals. Hepatic glycogen concentrations of non-diabetic and STZ-induced diabetic rats were significantly increased by all treatments at the end of 5 weeks. Acute intravenous infusion of OA in anaesthetized rats significantly increased Na+ excretion outputs of non-diabetic and STZ-induced diabetic rats without affecting urine flow, K+ or CI" excretion rates. Similarly, daily OA treatment (80 mg/kg, p.o.) significantly increased Na+ excretion rates of non-diabetic and STZ-induced diabetic rats throughout the 5 week experimental period without affecting urine flow, K+ or CI" excretion rates. By comparison with respective control animals, Short-term administrations of OA significantly (p<0.05) increased GFR of non-diabetic (2.88±0.14 vs 3.71±0.30 ml/min) and STZ-diabetic rats (1.81± 0.32 vs 3.07±0.16 ml/min, n=6 in all groups) with concomitant reduction of plasma creatinine concentrations. Acute and Short-term administrations of OA non-diabetic and STZinduced diabetic rats reduced mean arterial blood pressure by comparison with respective control animals. Discussion The results suggest that S. cordatum leaf derived OA not only has the potential to lower blood glucose in diabetes, but also has beneficial effects on kidney function and blood pressure. We suggest that the hypoglycaemic effects of OA mimic those of metformin as evidenced by the fact that neither of these treatments altered plasma insulin concentration of non-diabetic rats. OA-evoked increases in urinary Na+ outputs of STZ-diabetic rats and elevation of GFR suggest up-regulation of renal function by the triterpene. The findings are of considerable importance because they suggest the hypoglycaemic, renal and hypotensive effects of OA in the management of diabetes mellitus. Conclusion The results demonstrated that the oleanolic acid extracted from S. cordatum leaf has blood glucose-lowering effects comparable to standard anti-diabetic drugs in STZ-induced diabetic rats. Furthermore, OA augmented the hypoglycaemic effects of insulin in STZ-induced diabetic rats. These findings suggest that OA may have beneficial effects on some of the processes that are associated with renal derangement in STZ-induced diabetic rats. The results introduce the first in vivo evidence that OA ameliorates kidney function in STZinduced diabetic rats. Keywords: Renal function; diabetes mellitus; triterpenoids; oleanolic acid, hypoglycaemia / Thesis (M.Med.Sc.)-University of KwaZulu-Natal, 2008.