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MSc (Med) (Pharmaceutical Affairs), Faculty of Health Sciences, University of the Witwatersrand / Fifteen traditional medicinal plants, indigenous to southern Africa, that are used to treat various respiratory ailments were screened for their antimicrobial activity and their chemical profiles were documented. Acetone:methanol (1:1) extracts were prepared from the leaves, stems, roots, barks and thorns of the investigated plant species. The antimicrobial activity was determined against pathogens associated with respiratory conditions i.e. Moraxella catarrhalis, Bacillus cereus, Enterococcus faecalis, Klebsiella pneumoniae, Staphylococcus aureus, Candida albicans and Cryptococcus neoformans. The MIC values ranged from 0.08 mg/ml to 12 mg/ml. The two pathogens against which the most number of extracts obtained MIC values that were ≤ 1 mg/ml were Moraxella catarrhalis (68% of the extracts) and Bacillus cereus (56% of the extracts). The plant extracts that obtained the five lowest average MIC values against the respiratory pathogens were the root extracts of Terminalia sericea (0.69 mg/ml), leaf and stem extract of Chenopodium ambrosioides (1.04 mg/ml), leaf, stem and flower extract of Leucas martinicensis (1.10 mg/ml), leaf extract of Zanthoxylum davyi (1.29 mg/ml) and the leaf and stem extracts of Lantana rugosa (1.32 mg/ml). For the bioautographic assays, clear zones of inhibition were recorded for Lantana rugosa (leaves and stems) and Vitex rehmannii (leaves) against Staphylococcus aureus and Moraxella catarrhalis. The root extract of Ziziphus mucronata had a clear zone of inhibition against Staphylococcus aureus. The leaf and stem extracts of Chenopodium ambrosioides had a clear zone of inhibition against Moraxella catarrhalis. The chemical profiles that were recorded for the plant extracts comprised of HPLC and TLC chromatograms. The HPLC and TLC profiles resulted in the separation of the chemical constituents thus providing a chemical fingerprint for the plant extracts. Flavonoids were tentatively identified for Acacia sieberiana (leaves), Alepidea amatymbica (roots), Clematis oweniae (leaves), Clerodendrum glabrum (leaves), Heteromorpha arborescens (bark), Peucedanum caffrum (roots B), Vitex rehmannii (leaves) and Ziziphus mucronata (leaves). The TLC chromatograms qualitatively displayed good separation of the compounds present in the plant extracts. The antimicrobial activity recorded for the plant extracts validates their traditional uses to treat various respiratory infections and the chemical profiles provide a reference of the chemical profiles of the plant extracts that can be used in future investigations

Thesis (MSc (Biochemistry))--University of Limpopo (Medunsa Campus), 2009. / Background and Purpose The stem bark, roots and leaves of Sclerocarya birrea (S. birrea), {(A. Rich) Hochst}, subspecies caffra (Sond) Kokwaro are widely used in South Africa and some African countries as folk medicine in the treatment and management of a variety of human ailments, including diabetes mellitus. Although the blood glucose lowering effect of the stem bark extract of S. birrea have been confirmed using experimental animal models of diabetes, there is no clear understanding of the mechanism(s) whereby S. birrea stem bark extracts and/or their components exert their blood glucose lowering effects. The primary aim of the current study was to study the in vitro inhibitory effects of S. birrea stem bark extracts on the activities of selected diabetic related carbohydrate metabolizing enzymes (α-amylase, α-glucosidase and glucose 6-phosphatase). The current study also investigated the acute in vivo effect of S. birrea stem bark acetone extract on postprandial blood glucose levels after oral sucrose loading as well as the effect of S. birrea stem bark aqueous extract on hepatic glucose 6-phosphatase activity. In addition, the long term (21 days) effects of S. birrea stem bark acetone extract on fasting blood glucose levels, plasma insulin levels, plasma triglyceride and body weight in normal and alloxan induced diabetic rats were also investigated. Methods For in vitro studies: Crude hexane, acetone, methanolic and aqueous extracts of the stem bark extract of S. birrea were prepared by means of a sequential solvent extraction procedure and screened for inhibitory activities against human urinary α-amylase, rat pancreatic α-amylase, Bacillus stearothermophilus α-glucosidase and rabbit liver glucose 6-phosphatase using standard procedures for assaying the activities of these enzymes. IC50 values and mode of inhibition of extracts demonstrating appreciable inhibitory activity against α-amylase and α-glucosidase were determined and compared with those of acarbose, a known inhibitor of these two enzymes. The IC50 value and mode of inhibition of extracts demonstrating appreciable inhibitory activity against glucose 6-phosphatase were determined and compared with those of sodium orthovavadate and sodium tungstate, known inhibitors of glucose 6-phosphatase. In vivo studies: In vivo studies were conducted in normal and alloxan induced diabetic male WKY rats. Diabetes was induced in rats that had been fasted for 12 h by a single intraperitoneal injection of 140 mg/kg body weight of alloxan monohydrate freshly dissolved in sterile normal saline. The effect of S. birrea stem bark acetone extract on postprandial blood glucose level was determined in 18 h fasted diabetic and normal rats by administering orally, the plant extract (300 mg/kg) 30 minutes before an oral sucrose loading and measuring postprandial blood glucose levels after sucrose loading by means of a MediSense’s Optimum Xceed Glucometer (MOXG). In addition, rat intestinal dissacharidase (α-glucosidase/sucrase) activity was determined in homogenate of small intestine of rats sacrificed one hour after given orally either plant extract or acarbose. The in vivo effect of S. birrea stem bark extract on glucose 6-phosphatase was determined by measuring the activity of hepatic glucose 6-phosphatase at the end of the study. For the determination of the long term (chronic) effect of S. birrea stem bark crude acetone extract on blood glucose levels, body weight and water intake, alloxan induced diabetic and normal WKY rats were treated daily with S. birrea stem bark crude acetone extract (300 mg/kg) for 21 days. Fasting blood glucose levels and changes in body weight were determined on day 0, 7, 14 and 21 after initiation of treatment by means of a MOXG and gravimetrically respectively. Water intake was determined on the same days that blood glucose levels were determined by measuring the amount of water left overnight by each rat and subtracting this amount from the initial amount water given to each rat. Blood was also collected at the end of the study for the measurement of plasma glucose, triglyceride and insulin levels. Plasma glucose and plasma triglyceride levels were measured using commercially available kits based respectively on the glucose oxidase and the glycerol blanked methods (Beckman Coulter®’s UniCell DXC 800 Synchron® Clinical System). Plasma insulin levels were determined by means of an enzyme linked immunosorbant assay (ELISA) adapted to the Beckman Coulter® Ireland Inc’s UniCell DXI 800 Access® Immunoassay System. Results In vitro studies: The crude methanolic and acetone S. birrea stem bark extracts strongly inhibited both human urinary α-amylase and rat pancreatic α-amylase in a competitive manner. The inhibitory effect of the crude methanolic extract on both enzymes was significantly stronger than acarbose. Hexane and acetone crude extracts of the stem-bark of S. birrea demonstrated the highest percentage inhibition against B. stearothermophilus α-glucosidase. The mode of inhibition of the crude hexane extract on B. stearothermophilus α-glucosidase appeared to be a noncompetitive one. However, the this plant extract appeared to be a less potent inhibitor of α-glucosidase enzyme than acarbose. Rabbit liver glucose 6-phophatase was strongly inhibited by the crude aqueous S, birrea stem bark extract in a competitive manner. In vivo studies: Administration of S birrea stem bark acetone extract 30 min before oral sucrose loading significantly suppressed (P < 0.01) the rise in postprandial blood glucose levels in treated rats compared to control rats. The crude extract also decreased significantly the intestinal disaccharidase activity of experimental rats compared to control rats. These observations suggest that the in vitro inhibitory effects of the crude hexane extract on α-glucosidase enzymes are applicable in vivo Daily, continuous oral treatment of alloxan–induced diabetic and normal WKY rats with S. birrea stem bark extract for 3 weeks resulted in significant reductions in fasting blood glucose levels and water intake of treated diabetic rats compared with diabetic controls. The extract, however, failed to bring about any significant change in the body weight, plasma insulin levels, plasma triglyceride levels and hepatic glucose 6-phosphatase of treated diabetic rats compared to diabetic control rats Conclusions The results of the current study suggest that the observed in vitro inhibitory effect of S. birrea stem bark acetone extract on alpha glucosidase enzymes are applicable in vivo whereas the observed in vitro inhibitory effect of S. birrea stem bark aqueous extract on glucose 6-phosphatase are not applicable in vivo. Furthermore, in the current study S. birrea stem bark acetone extract appears to lower blood glucose levels of alloxan induced diabetic rats without increasing their plasma insulin levels. Thus, it can be concluded on the basis of the current study that S. birrea stem bark acetone and hexane extracts exert their blood glucose lowering effect in alloxan induced diabetic rats in part, through inhibition of intestinal brush border α-glucosidase enzymes.

Thesis (MSc (Biochemistry))--University of Limpopo (Medunsa Campus), 2010. / Background: Clausena anisata (C. anisata) (Willd) Hook [Family: Rutaceae] is one of the South African indigenous medicinal plant whose blood glucose lowering effect has been demonstrated in animal models of diabetes mellitus. However, the mechanism(s) by which extracts of these plants exert their blood glucose lowering effect have not been investigated Objectives of the study: The objectives of the current study were to investigate in vitro inhibitory effects of different C. anisata leaf extracts on the activities of human urinary α-amylase, Bacillus stearothermophilus α-glucosidase and rat hepatic glucose 6-phosphatase and to characterize the enzyme inhibitory effect of the extracts on these enzymes with respect to the mode of inhibition (type of inhibition) and IC50 values (measure of inhibition potency). Another objective of the study was to confirm the enzyme inhibitory effects of C. anisata in vivo by measuring postprandial glucose levels in alloxan induced diabetic rats after oral administration of sucrose. Results: Aqueous and methanolic extracts of C. anisata leaves inhibited human urinary α-amylase with IC50 values of 1947 ± 50 and 2436 ± 62 µg/ml respectively. Inhibitions of α-amylase by these extracts were however, significantly less than that of the reference drug acarbose (84 ± 11 µg/ml) (P < 0.001). The mode of inhibition of these extracts on human urinary α-amylase appears to be a reversible non-competitive one. Acetone and hexane extracts of C. anisata inhibited Bacillus stearothermophilus α-glucosidase with IC50 values of 1020 ± 32 and 2068 ± 59 µg/ml respectively. Inhibition of Bacillus stearothermophilus α-glucosidase by these two extracts was also significantly less than that produced by acarbose (36 ± 11 µg/ml) (P < 0.001). The mode of inhibition of Bacillus stearothermophilus α-glucosidase by the acetone extract was found to be reversible competitive in this case. Aqueous and methanolic extracts of C. anisata leaves also inhibited hepatic glucose 6-phosphatase with IC50 values of 493.6 ± 12 and 1012 ± 58 µg/ml respectively. In this case the effect of the aqueous extract was significantly less than that of the reference inhibitor of glucose 6-phosphatase, sodium vanadate (1651 ± 46 µg/ml) (P < 0.05). The mode of inhibition of glucose 6-phosphatase by C. anisata aqueous leaf extract was found to be irreversible. Furthermore, oral administration of C. anisata acetone leaf extract to normal and alloxan induced diabetic rats, 30 minutes before sucrose loading failed to prevent the rise in postprandial glucose levels in these animals. Conclusions: Although both C. anisata aqueous and hexane leaf extract inhibited human urinary α-amylase and Bacillus stearothermophilus α-glucosidase in vitro, this does not appear to be the case in vivo. C. anisata aqueous leaf extract appeared to be a more potent inhibitor of rat hepatic glucose 6-phosphatase than the known inhibitor of the catalytic subunit of this multi-component enzyme system.

El principal objectiu d'aquest treball es avaluar els efectes d'un additiu comercial XT (5% carvacrol, 3% cinamaldehide, 2% oleoresina d capsicum) sobre els rendiments productius i diferents paràmetres de la fisiologia digestiva del garrí deslletat precoçment. Un altre objectiu d'aquest treball es avaluar les possibles interaccions del XT amb altres ingredients, nutrients i additius de la dieta. Aquest treball s'ha d'entendre com a part d'un ampli pla de recerca multicentric organitzat per la companyia Pancosma. En concret hem avaluat i) l'efecte del XT als paràmetres mencionats depenent del nivell i font de proteïna, ii) la possible interacció entre l'XT i l'àcid fòrmic, i la comparació de l'efecte del XT amb l'acció de l'avilamicina i el butirat sòdic. Finalment, després de tres anys de col·laboració i donat l'interès de la companyia en desenvolupar nous productes basats en extractes de plantes, hem desenvolupat un mètode in vitro per testar el poder antimicrobià d'un ampli ventall de substàncies derivades de plantes. Al treball in vitro, el nostre objectiu ha sigut desenvolupar un mètode molt simple però realista, utilitzant el contingut de diferent trams del tracte intestinal, obtingut dels porcs sense cap modificació, i incubant-lo curts períodes de temps.Resultats productiusEls resultats productius són molt variables entre experiments. Aquestes variacions són degudes probablement a l'ús de diferent instal·lacions, edats i estats de salut dels animals i la diferent composició de les dietes bassals.Mesures fisiològiques i físiquesLa digestibilitat ileal i rectal i el pH en les diferents part del tracte gastrointestinal s'han estudiat de manera sistemàtica a les tres proves in vivo però no s'han obtingut resultats consistents. Tanmateix, la inclusió de extractes de plantes a la segona prova va provocar un alentiment del buidament gàstric realcionat amb un augment del pH de l'estomac.Poblacions microbianes El resultat més consistent de tots els obtinguts es l'augment de lactobacillus amb la inclusió del XT a les dietes. Malauradament, la rellevància d'aquest augment no està gens clara perquè no va tenir relació directa amb cap benefici productiu. La inclusió del XT ha afectat també altres paràmetres microbians: la concentració de bases púriques i els perfils d'àcids grassos volàtils. Aquest resultats no són molt consistents i de vegades contraris.Paràmetres epitelialsS'han estudiat els efectes del XT a l'estructura epitelial però una vegada més els resultats són molt variables depenent de la prova. De totes maneres queda clar que l'XT exerceix una gran influencia sobre certs paràmetres immunes del epiteli, i s'han de continuar investigant amb tècniques més especifiques.Estudis in vitroEl mètode in vitro s'ha utilitzat amb èxit pe compara diferents additius. Les variacions de fermentació in vitro no només depenen del additiu utilitzat, sinó també de l'edat de l'animal i de la part del tracte gastrointestinal utilitzada d'on s'obté l'inocul. Aquestes variacions s'han d'analitzar amb deteniment.D'aquests estudis podem concloure que les dosis comercials de XT no presenten efectes antimicrobians directes sobre les poblacions microbianes estudiades (lactobacillus i enterobacterias). Utilitzant el contingut de jejú com inocul, es necessiten dosis properes a 10000 ppm per obtenir efectes antimicrobians. D'altre banda, amb dosis més baixes de les substàncies pures s'aconsegueixen efectes similars. Aquestes dosis varien entre 500 i 3000 ppm de carvacrol i cinamaldehid, depenent de la part del tracte gastrointestinal estudiada. Amb tots els productes, la dosis mínima necessària per inhibir la fermentació es sempre menor amb el contingut del jejú. / The main objective of this PhD dissertation is to evaluate the effects of the commercial additive XT (5% carvacrol, 3% cinnamaldehyde, 2% capsicum oleoresin) on productive performance and on different parameters of normal digestive physiology of the early weaned pig: digestibility, pH, epithelial structure, bacterial populations and metabolic activity. It is also an objective of this work to evaluate possible interactions of XT with other ingredients, nutrients and additives included in the diet. This work must be understood in a broader multi-centric research plan organized by the company Pancosma. In particular, the experiments here presented evaluate i) the effects of XT on the above mentioned parameters depending on the CP level and source, ii) the possible interaction between XT and formic acid, and finally the comparison of the effects of XT with the action of avylamycin and butyrate. After three years of collaboration and given the interest of the company in developing new products based on plant extracts, we developed an in vitro methodology to test the antimicrobial effects of a wide range of plant derived substances. Concerning the in vitro method, our objective was to develop a very simple but realistic method able to obtain significant results, using crude intestinal content obtained from the pigs and incubating it for short periods.Productive performanceThe performance results were very variable among the experiments. These variations were probably due to the use of different facilities, age and health status of the animals and the different composition of the basal diets.Physiologic and physical parametersIleal and whole tract digestibility and pH measurements in different parts of the gastrointestinal tract were systematically studied in the three in vivo trials but no consistent effects of including plant extracts were found. However, plant extracts inclusion in the diet in the second trial resulted in a decrease of gastric emptying rate and an increase of pH. Microbial populations The most consistent result in the three experiments was an increase in lactobacilli counts with the inclusion of XT in the diets. However, the relevance of this higher intestinal lactobacilli content is not clear, since there was no direct relation with productive benefits. XT inclusion also had an effect on other microbial parameters: purine bases concentration and VFA profile. However, those results were not very consistent and often were highly controversial.Epithelial parameters The effects of XT on the epithelial structure were studied and, once more, the results were very variable depending on the trial. However, a high influence of XT was found on some immune parameters measured in the epithelium and in the lamina propia, results that encourage continuing investigating these effects with more specific techniques.In vitro studies The in vitro method was successfully used to compare different additives. Variations in in vitro fermentation were found not only depending on the additive used but on the age of the animal and on the gastrointestinal tract part used as source of the inoculum. These variations should be studied in more detail in the future.From these studies, we can conclude that the recommended commercial dose of XT presents no direct antimicrobial effect on the studied populations (lactobacilli and enterobacteria). Doses of near to 10000 ppm are needed to obtain antimicrobial effects in jejunum content. However, lower doses were needed when the pure substances instead of the XT mixture were used. These doses were between 500 and 3000 ppm for carvacrol and cinnamaldehyde, depending on the gastrointestinal tract part studied. The minimum dose of all studied substances to produce antimicrobial effects was always lower for the jejunum than for stomach or cecum content.

Thesis (Ph. D.)--Michigan State University. Dept. of Food Science and Human Nutrition, 2008. / Title from PDF t.p. (viewed on Mar. 27, 2009). Includes bibliographical references. Also issued in print.

Thesis (MSc (Paraclinical Sciences))--University of Pretoria, 2008. / Includes bibliographical references. Also available in print format.

Thesis (M.Sc. (Pharmacology)) -- Mahidol University, 1978. / Supported by the Faculty of Dentistry, Mahidol University and the National Research Council.

Thesis (M.Sc. (Organic Chemistry)) -- Mahidol University, 1976. / Supported by University Development Commission.