In this investigation the chemistry of three southern African plants used for medicinal purposes was investigated. The plants were Dioscorea dregeana, Avonia rhodesica and Equisetum ramossisimum. Extracts of all three of these plants have been found to be active on the central nervous system. The structures of the compounds isolated were determined by using 1H and 13C n.m.r., i.f., UV-VIS, - mass spectroscopy and chemical methods. D. dregeana yielded two alkaloids and three aromatic compounds. A. rhodesica contained a large amount of wax which was analysed by GC-MS and its distribution and physical nature on the surface of the leaves was determined by SEM (scanning electron microscopy). This plant also contained two sterols. Equisetum ramossisimum extracts contained a carotenoid and several porphyrins, as well as large amounts of silica. A DTSA X-ray microanalysis system (which was a component of the scanning electron microscope) was used to determine the distribution of silica in the stem. / Thesis (M.Sc.)-University of Natal, Durban, 1998.

Ho, Wing Shan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 116-137). / Abstracts in English and Chinese. / Acknowledgements --- p.i / Abstract --- p.ii / Abstract (Chinese Version) --- p.v / Table of Contents --- p.vii / List of Figures --- p.x / List of Tables --- p.xi / List of Abbreviations --- p.xii / Chapter Chapter One: --- General Introduction / Chapter 1.1 --- Respiratory Syncytial Virus (RSV) --- p.1 / Chapter 1.2 --- RSV biology --- p.2 / Chapter 1.3 --- RSV strains --- p.10 / Chapter 1.4 --- RSV pathogenesis and host antiviral responses --- p.11 / Chapter 1.5 --- Prevention of RSV infection --- p.13 / Chapter 1.5.1 --- Vaccines --- p.13 / Chapter 1.5.2 --- Passive anti-RSV antibodies --- p.17 / Chapter 1.6 --- Treatment for RSV infections --- p.20 / Chapter 1.6.1 --- Ribavirin (Virasole®) --- p.20 / Chapter 1.6.2 --- Other antiviral strategies --- p.21 / Chapter 1.6.2.1 --- Attachment inhibitors --- p.22 / Chapter 1.6.2.2 --- Fusion inhibitors --- p.23 / Chapter 1.6.2.3 --- Replication inhibitors --- p.25 / Chapter 1.6.2.4 --- Ethnobotanic medicines --- p.28 / Chapter 1.6.2.4.1 --- Anti-RSV medicinal plant components --- p.31 / Chapter 1.6.2.4.1.1 --- Phenolics and polyphenols --- p.31 / Chapter 1.6.2.4.1.2 --- Flavonoids --- p.32 / Chapter 1.6.2.4.1.3 --- Terpenoids and essential oils --- p.34 / Chapter 1.6.2.4.1.4 --- Lectins --- p.34 / Chapter 1.6.2.4.1.4.1 --- General introduction to lectins --- p.34 / Chapter 1.6.2.4.1.4.2 --- Historical aspects of lectins --- p.35 / Chapter 1.6.2.4.1.4.3 --- Applications of lectins --- p.36 / Chapter 1.7 --- Objectives of the project --- p.37 / Chapter Chapter Two: --- Screening of medicinal plants and phytochemicals for antiviral activity against RSV / Chapter 2.1 --- Introduction --- p.39 / Chapter 2.2 --- Materials and methods --- p.47 / Chapter 2.2.1 --- Medicinal plants and phytochemicals --- p.47 / Chapter 2.2.2 --- Plant extracts preparation --- p.48 / Chapter 2.2.2.1 --- Aqueous extracts --- p.48 / Chapter 2.2.2.2 --- Ethanol extracts --- p.48 / Chapter 2.2.3 --- Cell and virus --- p.49 / Chapter 2.2.4 --- Endpoint titration of RSV infectivity --- p.50 / Chapter 2.2.5 --- Cytotoxicity test --- p.50 / Chapter 2.2.6 --- Antiviral assay --- p.52 / Chapter 2.3 --- Results --- p.53 / Chapter 2.4 --- Discussion --- p.58 / Chapter Chapter Three: --- "Mechanistic studies of anti-RSV actions of various fractions of Adina pilulifera, and daphnoretin, a purified compound from Wikstroemia indica" / Chapter 3.1 --- Introduction --- p.60 / Chapter 3.2 --- Materials and methods --- p.65 / Chapter 3.2.1 --- Fractionation of A. pilulifera ethanol extract --- p.65 / Chapter 3.2.2 --- Cell and virus --- p.65 / Chapter 3.2.3 --- Cytotoxicity test --- p.65 / Chapter 3.2.4 --- Endpoint titration of RSV by TCID50 method --- p.66 / Chapter 3.2.5 --- Antiviral study by CPE reduction assay --- p.66 / Chapter 3.2.6 --- Endpoint titration of RSV by plaque assay --- p.66 / Chapter 3.2.7 --- Antiviral study by plaque reduction assay --- p.67 / Chapter 3.2.8 --- Mode of antiviral action study --- p.68 / Chapter 3.3 --- Results --- p.70 / Chapter 3.4 --- Discussion --- p.76 / Chapter Chapter Four: --- Antiviral activity of Narcissus tazetta proteins / Chapter 4.1 --- Introduction --- p.81 / Chapter 4.2 --- Materials and methods --- p.88 / Chapter 4.2.1 --- Crude proteins extraction from Narcissus tazetta cultivar --- p.88 / Chapter 4.2.2 --- Separation of proteins with affinity column --- p.88 / Chapter 4.2.3 --- Gel filtration of protein fractions on Superose column --- p.89 / Chapter 4.2.4 --- Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) --- p.89 / Chapter 4.2.5 --- Electroblotting and N-terminal amino acid sequence analysis --- p.90 / Chapter 4.2.6 --- Protein concentration determination --- p.90 / Chapter 4.2.7 --- Isolation and purification of N. tazetta lectin (NTL) --- p.91 / Chapter 4.2.8 --- Antiviral activities of N. tazetta proteins and NTL --- p.92 / Chapter 4.2.8.1 --- Cell and virus --- p.92 / Chapter 4.2.8.2 --- Cytotoxicity test --- p.92 / Chapter 4.2.8.3 --- Endpoint titration of RSV by TCID50 method --- p.92 / Chapter 4.2.8.4 --- Antiviral study by CPE reduction assay --- p.92 / Chapter 4.2.8.5 --- Endpoint titration of RSV by plaque assay --- p.92 / Chapter 4.2.8.6 --- Antiviral study by plaque reduction assay --- p.93 / Chapter 4.2.8.7 --- Mode of antiviral action study --- p.93 / Chapter 4.3 --- Results --- p.94 / Chapter 4.4 --- Discussion --- p.107 / Chapter Chapter Five: --- General Discussion and Conclusions --- p.111 / References --- p.116

Thesis (Doctoral)--Freie Universität Berlin. / Includes bibliographical references (p. 336-361) and index.

University of Macau / Institute of Chinese Medical Sciences

University of Macau / Institute of Chinese Medical Sciences

D. Tech. Pharmaceutical Sciences.

The use of traditional medicine through the use of medicinal plants in Africa and especially in South Africa has long been considered an important characteristic of people's daily lives and socio-cultural heritage. Cotyledon Orbiculata is among the medicinal plants that are used by South African traditional practitioners for the treatment of epilepsy and painful conditions such as corns, warts, toothache, earache, boils and various other ailments. However, the claim of therapeutic successes of medicinal plants by traditional medicine practitioners are hardly subjected to scientific scrutiny. This study therefore, investigated the anti-epileptic property of Cotyledon Orbiculata by studying the effects of the methanol extract of the plant against chemically induced seizures by pentylenetetrazole, picrotoxin, bicuculline and N-methyl-DL-aspartic acid in mice. The study also investigated the analgestic effects of Cotyledon Orbiculata by studying the effect of the plant extract on pain induced by acetic acid and hot plate thermal stimulation.

Thesis (Doctoral)--Freie Universität Berlin. / Includes bibliographical references (p. 336-361) and index.

In Africa, use of medicinal plants for the treatment of diabetes is very common. However, efficacy on co-administering of medicinal plants with therapeutic drugs hasn't been fully determined, especially for African medicinal plants. The current study focused on assessing the in vitro modulation effects of three popular African medicinal plants, namely: Aloe ferox, Sutherlandia frutescens and Prunus africana (including five commercial preparations containing these medicinal plants) on two of the most important anti-diabetic drug metabolising enzymes, Cytochrome P450 (CYP450) 2C9 and CYP3A4 and a key drug efflux transporter, P-glycoprotein (P-gp). Vivid® microsome-based screening kits were used to assess inhibitory potency of plants preparations on CYP2C9 and CYP3A4 enzymes activities. The study showed that P. africana was a more potent inhibitor of CYP2C9 and CYP3A4 activity than the corresponding positive controls Ginkgo biloba and St. John's wort, which are known to cause clinically significant drug-herb interactions. S. frutescens leaf extract demonstrated potent to moderate inhibition on both the tested CYP activities, while its commercial products (Promune® and Probetix®) possessed moderate to mild inhibitory effects on the activities of both CYPs. Potent inhibitory effect on CYP2C9 and CYP3A4 was seen with Aloe Ferox®. Prosit® and Aloes powder® showed potent to moderate inhibition on CYP2C9 activity and moderate to mild inhibition on CYP3A4 activity. In addition to CYP450 activity, the present study also investigated the effects of the selected medicinal plant products on the activity of the main drug efflux protein, P-gp. A screening assay was specifically developed to assess the potential for herbal remedies to interact with P-gp mediated drug absorption. The assay is based on the principle of the reversal of drug resistance in modified Caco-2 cells specifically altered to express high iv efflux protein activity. These cells display a multidrug resistance phenotype and the addition of a plant extract containing a P-gp inhibitor or substrate will inhibit or compete with any cytotoxic drug and consequently reverse the drug resistance. The suitability of the assay was confirmed using a known P-gp inhibitor. The study observed that the anti-proliferation effect of vinblastine was significantly enhanced in vinblastine-resistant Caco-2 cells, which have high P-gp expression, when they were exposed to the selected African herbal preparations. This observation indicates that the studied plant preparations may alter P-gp functionality and therefore lead to interference with the absorption of co-administered drugs. The outcomes of this study provide useful information on whether there are any potential drug-herb interactions between the commonly used African medicinal plants and oral anti-diabetic drugs, at the level of CYP and P-gp drug metabolism and could contribute to better therapeutic management of Type II diabetics. However these predicted interactions will need to be verified in a clinical setting.

Commercial marrubiin, aqueous and organic extracts of Leonotis leonurus were tested in vitro for their anticoagulant and antiplatelet activities. The aqueous extract inhibited platelet aggregation by 69.5 percent (100 μg/mL), while the organic extract (100 μg/mL) and marrubiin (5 μg/mL) showed 92.5 percent and 91.6 percent inhibition, respectively, by inhibiting the binding of fibrinogen to glycoprotein IIb/IIIa receptor in a concentration dependent manner. The extracts significantly prolonged activated partial thromboplastin time compared to untreated plasma controls. Fibrin and D-Dimer formation were drastically decreased. The extracts and marrubiin concentration-dependently inhibited calcium mobilization induced by collagen and thrombin. The formation of thromboxane A2 was also significantly reduced by both the extracts and marrubiin. Protein secretion and platelet adhesion were significantly reduced by both the extracts and marrubiin. The organic extract and marrubiin showed a more pronounced effect than the aqueous extracts in all the in vitro assays. The ex-vivo animal model confirmed the results obtained in vitro. Similar to the in vitro studies, activated partial thromboplastin time clotting time was prolonged by marrubiin and the number of aggregated platelets were significantly reduced relative to aspirin. The findings reflect that marrubiin largely contributes to the organic extract's anticoagulant and antiplatelet effect in vitro. INS-1 cells were cultured under normo- and hyperglycaemic conditions. Marrubiin and the two Leonotis leonurus extracts were screened for anti-diabetic activity in vitro. The stimulatory index of INS-1 cells cultured under hyperglycaemic conditions was significantly increased by 60 percent and 61 percent (p<0.01; n=5) in cells exposed to the organic extract (10 μg/mL) and marrubiin (500 ng/mL), respectively, relative to the normoglycaemic conditions. The gene expression of insulin was significantly increased by 76.5 and 71 percent, and of glucose transporter-2 by 93 and 92.5 percent for marrubiin and the organic extract, respectively, under the same conditions stipulated above (p<0.01; n=4). The extract and marrubiin similarly showed an increase in respiratory rate under hyperglycaemic conditions. Marrubiin increased insulin secretion, HDL-cholesterol, while it decreased total cholesterol, LDL-cholesterol and the atherogenic index in the in vivo rat model.