Thesis (DMed)--Stellenbosch University, 2015 / ENGLISH ABSTRACT: Introduction The increasing intake of traditional medicines among HIV/AIDS patients in sub-Saharan Africa needs urgent consideration by clinicians and other healthcare providers since the safety of such medications are unknown. The pharmacokinetic parameters - Absorption, Distribution, Metabolism and Elimination (ADME) play important role in the safety evaluation of drugs, thus implicating drug metabolizing enzymes and transporters as critical indicators for herb-drug interactions. The objective of this study was to evaluate the risk potential of seven herbal medicines commonly consumed by HIV/AIDS patients for drug interactions applying in vitro models. In this study, inhibition and induction effects of the herbal medicines on cytochrome P450s (CYPs) 1A2, 2C9, 2C19, 2D6 and 3A4 as well as P-glycoprotein (P-gp) were investigated. Methods Herbal medicines – Lessertia frutescens, Hypoxis hemerocallidea, Kalanchoe integra and Taraxacum officinale were sourced from Medico Herbs, South Africa were identified by experts from Compton Herbarium, South African National Biodiversity Institute, Cape Town. Moringa oleifera, Echinacea purpurea and Kalanchoe crenata were obtained from the repository of the National Centre for Natural Product Research (NCNPR), University of Mississippi, USA. Reversible inhibitory effect of aqueous and methanol herbal extracts were evaluated in recombinant CYPs applying the fluorescent metabolites at specified excitation/emission wavelengths; CYP1A2 (3-cyano-7-hydroxycoumarin (CHC); 405/460 nm), CYP2C9, CYP2C19 and CYP3A4 (7-hydroxy-4-(trifluoromethyl)-coumarin (HFC); 405/535 nm) and CYP2D6 (7-hydroxy-4-(aminomethyl)-coumarin (HAMC); 390/460 nm). Comparative studies in human liver microsomes (HLM) and recombinant CYPs were conducted to investigate the inhibitory effect of methanol herbal extracts and fractions on 6β testosterone hydroxylation activity. Time dependent inhibitory (TDI) effect of the herbal extracts were evaluated applying the IC50 shift fold, normalized ratio and the NADPH-, time- and concentration-dependent approaches. Influence of herbal extracts on metabolic clearance of testosterone was assessed in both HLM and human hepatocytes. The effects of each herbal extract on expression of CYP1A2, CYP3A4 and MDR1 genes were evaluated in activated human pregnane X receptor (PXR) co-transfected HepG2 cells. Finally, the inhibitory effect of herbal extracts on P-gp was assessed using the calcein-acetoxymethyl ester (calcein-AM) uptake and the digoxin radiolabelled substrates in MDCKII-MDRI cells. Results The aqueous extracts of Moringa oleifera, Kalanchoe integra, Kalanchoe crenata, Echinacea purpurea and Lessertia frutescens demonstrated high risk of in vivo inhibition on CYPs 3A4 and 1A2 with Cmax/Ki >1.0. Methanol extracts of these herbal medicines also indicated potential risk of reversible drug interaction. The methanol extracts of M. oleifera, K. crenata and L. frutescens showed strong TDI effect on CYP3A4 with IC50 shift fold >1.5 and normalised ratio <0.7. Moringa oleifera intermediately reduced intrinsic clearance of testosterone in human hepatocytes (2 ≤ AUC ratio ≤ 5) when scaled up to humans. Methanol extracts of Echinacea purpurea up-regulated the expression of CYP1A2, CYP3A4 and MDR1 genes in activated PXR. Kalanchoe crenata and Echinacea purpurea indicated strong inhibition on P-gp by reducing transport of digoxin across hMDR1-MDCKII cell monolayer from basolateral to apical with IC50 values of 18.24 ± 2.52 μg/mL and 24.47 ± 4.97 μg/mL, respectively. Conclusion The herbal medicines especially M. oleifera, K. integra and E. purpurea have the potential to cause herb-drug interaction in vivo if sufficient hepatic concentration is achieved in humans. / AFRIKAANSE OPSOMMING: Inleiding Die verhoogde inname van tradisionele medisynes onder MIV/VIGS-pasiënte in sub-Sahara-Afrika verg dringend oorweging deur klinici en ander gesondheidsorgverskaffers, aangesien die veiligheid van sodanige medikasies onbekend is. Die farmakokinetiese parameters – Absorpsie, Distribusie, Metabolisme en Eliminasie (ADME) – speel ’n belangrike rol by die veiligheidsevaluering van geneesmiddels, en impliseer gevolglik geneesmiddel-metaboliserende ensieme en vervoerders as kritiese indikators vir krui-geneesmiddel-interaksies (HDI). Die oogmerk van hierdie studie is om die risikopotensiaal van sewe kruiemedisynes wat algemeen deur MIV/VIGS-pasiënte geneem word, vir geneesmiddel-interaksies te evalueer deur in vitro-modelle te gebruik. In hierdie studie is die inhiberings- en induseringsuitwerkings van die kruiemedisynes op sitochroom P450’s (verkort na CYP’s) 1A2, 2C9, 2C19, 2D6 en 3A4, sowel as P-glikoproteïen (P-gp), ondersoek. Metodes Kruiemedisynes – Lessertia frutescens, Hypoxis hemerocallidea, Kalanchoe integra en Taraxacum officinale – is van Medico Herbs, Suid-Afrika, bekom en deur kundiges van die Compton-herbarium, by die Suid-Afrikaanse Nasionale Biodiversiteitsinstituut, Kaapstad, geïdentifiseer. Moringa oleifera, Echinacea purpurea en Kalanchoe crenata is van die bewaarplek van die Nasionale Sentrum vir Natuurlike Produknavorsing (NCNPR) aan die Universiteit van Mississippi in die VSA verkry. Die omkeerbare inhiberende uitwerking van kruie-ekstrakte in water en metanol is in rekombinante CYP’s geëvalueer deur die gebruik van die fluoresserende metaboliete op gespesifiseerde opwekkings-/emissiegolflengtes; CYP1A2 (3-siaan-7-hidroksikumarien (CHC); 405/460 nm), CYP2C9, CYP2C19 en CYP3A4 (7-hidroksi-4-(trifluoormetiel)-kumarien (HFC); 405/535 nm) en CYP2D6 (7-hidroksi-4-(aminometiel)-kumarien (HAMC); 390/460 nm). Vergelykende studies van menslikelewermikrosome (HLM) en rekombinante CYP’s is uitgevoer om die inhiberende uitwerking van metanolkruie-ekstrakte en -fraksies op 6β-testosteroonhidroksileringsaktiwiteit te ondersoek. Die tydafhanklike inhiberende uitwerking (TDI) van die kruie-ekstrakte is geëvalueer deur gebruikmaking van die IC50-verskuiwingsvou-, die genormaliseerdeverhoudings- en die NADPH-, tyd- en konsentrasieafhanklike benaderings. Die invloed van kruie-ekstrakte op metaboliese testosteroonverheldering is in beide HLM en menslike hepatosiete geëvalueer. Die uitwerkings van elke kruie-ekstrak op die uitdrukking van CYP1A2-, CYP3A4- en MDR1-gene is in geaktiveerde menslike pregnaan-X-reseptor(PXR)-, ko-getransfekteerde HepG2-selle geëvalueer. Laastens is die inhiberende uitwerking van kruie-ekstrakte op P-gp geëvalueer, met gebruikmaking van die kalsien-asetoksimetiel-ester (kalsien-AM)-opname en die digoksien- radiogemerkte substrate in MDCKII-MDRI-selle. Resultate Die ekstrakte in water van M. oleifera, K. integra, K. crenata, E. purpurea en L. frutescens het ’n hoë risiko van in vivo-inhibering op CYP’s 3A4 en 1A2 met Cmaks/Ki >1.0 getoon. Ekstrakte van hierdie kruiemedisynes in metanol het verder potensiële risiko van omkeerbare geneesmiddelinteraksie getoon. Die ekstrakte van M. oleifera, K. crenata en L. frutescens in metanol het sterk TDI-uitwerking op CYP3A4 met IC50-verskuiwingsvou >1.5 en genormaliseerde verhouding <0.7 getoon. M. oleifera het intermediêre vermindering van intrinsieke testosteroonverheldering in menslike hepatosiete (2 ≤ AUC verhouding ≤ 5) tot gevolg wanneer die skaal na mense verhoog word. Ekstrakte van E. purpurea in metanol het die uitdrukking van CYP1A2-, CYP3A4- en MDR1-gene in geaktiveerde PXR opgereguleer. K. crenata en E. purpurea het sterk inhibering van P-gp getoon deur die vervoer van digoksien deur die hMDR1-MDCKII-selmonolaag van basolateraal tot apikaal met IC50-waardes van onderskeidelik 18.24 ± 2.52 μg/mL en 24.47 ± 4.97 μg/mL te verminder. Gevolgtrekking Kruiemedisynes, veral M. oleifera, K. integra en E. purpurea, het die potensiaal om HDI in vivo te veroorsaak indien voldoende hepatiese konsentrasie by mense bereik word.

M. Tech. Entrepreneurship / The purpose of this study is to develop a consumer profile of traditional Chinese medicine consumption in South Africa. The research was based upon a nomethetic survey, a total sample size of 321 respondents was selected according to the convenience sampling technique to participate in the research. Descriptive data analysis was performed indicating that behaviour control and social impact norms primarily influencing the purchase of traditional Chinese medicine.

published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / Chemistry / Master / Master of Philosophy

No description available.

<p>Infusions, decoctions, alcoholic preparations and other dosage forms of Artemisia afra are frequently used in South African traditional medicine. Generally when these preparations are made without applying good manufacturing practices they do not meet microbial quality control standards, safety and toxicity criteria and encourage poor patients compliance. To overcome the aforementioned disadvantages of traditional dosage forms a sold dosage form, i.e. a table might be recommended. The first objective of this study was to formulate and manufacture a rapid release tablet dosage of Artemisia afra that would contain an amount of plant material equivalent to that found in its traditional liquid dosage forms and that would meet conventional pharmaceutical standards. The second objective was to conduct a pilot study to obtain a preliminary profile of the bioavailability of select flavonoids presents in both the tablet and traditional liquid preparation of Artemisia afra in humans.</p>

Three plant species (Phylica paniculata Willd., Pergularia daemia Forssk. and Monsonia / Thesis (M.Sc.)-University of KwaZulu-Natal, Pietermaritzburg, 2006.

Mini-dissertation submitted in partial compliance with the requirements for the Master's Degree in Technology: Homoeopathy, Durban University of Technology, 2007. / The first objective of this study was to determine the symptomatology that the plant remedy Peucedanum galbanum 30CH, produced in healthy individuals, so that it could be prescribed according to the Law of Similars, as required by homoeopathy. The second objective was to analyse this symptomatology in relation to the doctrine of signatures. It was hypothesised that Peucedanum galbanum 30CH would produce symptomatology in healthy individuals which would correlate to the doctrine of signatures of the plant. / M

Ampelopsis grossedentata is a wildly used herb in South China as sleep aid beverage for many years. Yet the active ingredients and mechanisms of this herb were unknown. In the present study, extract from Ampelopsis grossedentata which we named ECBRC-AG, and one of its active ingredient myricetin were proved having significant hypnotic/sedative effects in multiple animal models. ECBRC-AG shortened sleep latency, increase NREM sleep and decrease locomotor activity when treated before the onset of light period in rats. ECBRC-AG could decrease active awake and increase REM sleep in the late part of light period. ECBRC-AG also decreased the caffeine induced hyperactivity in rats. Among the three suspected active ingredients from ECBRC-AG, myricetin showed similar active profile with ECBRC-AG. Myricetin increased NREM and REM sleep, decreased sleep latency, decreased locomotor activity and also active awake. All the above evidences have implicated that myricetin is the most important active ingredient of ECBRC-AG ECBRC-AG and myricetin did not show any obvious side effects on rats. / Based on these findings, we propose that myricetin facilitates GABA function on PVN neurons through a T-type calcium channel and CaM-KII mechanism. The hypnotic/sedative effects of ECBRC-AG and myricetin are mediated by PVN. ECBRC-AG treatment decreased corticosterone levels in rats, which also indicated that PVN/HPA axis was the target of these herbal derivates. PVN has broad interactions with GABAergic, hypocretinergic, cytokine and NPY system and all these systems are proved to be deeply involved in sleep regulation. / In conclusion, the present study has identified that myricetin is the most important active ingredient of the herbal extract ECBRC-AG. We confirmed the hypnotic/sedative effects of ECBRC-AG and myricetin on rats, and also revealed the different action profiles of these herbal derivates compared with zolpidem. T-type calcium channels and the HPA axis were shown to be involved in the mechanisms of ECBRC-AG and myricetin, indicating that they may be the new targets for insomnia treatment with these herbal derivates. / Insomnia is the most common sleep disorder and affects about one third of the general population. Insomnia is always combined with physical and mental illness, as either a consequence or a contributing factor. Insomnia produces sleepiness, impairment in psychomotor performance, absenteeism, frequent accidents, memory impairment and a high risk of depression. Pharmacologic therapies are the most important interventions for insomnia. However, the currently available hypnotics are associated with residual effects and risks of abuse and dependence. More efficient and safe hypnotics are needed. / The DNA array and RT-PCR studies revealed that GABA, hypocretin, cytokine and NPY systems were involved in the mechanisms of ECBRC-AG and myricetin. In calcium imaging study, we found that myricetin induced a transient Ca 2+ influx in the primary culture of rat hypothalamus neurons. This Ca2+ influx could be blocked by T-type channel blocker mibefradil. RT-PCR study also showed that ECBRC-AG and myricetin treatment changed the mRNA expression level of T-type calcium channel al G subunit in rat hypothalamus. The present results are consistent with our previous study showing that myricetin enhanced GABA function in the neurons of rat hypothalamic paraventricular nucleus (PVN), and that blocking CaM-KII pathway eliminated this effect. / Zhang, Xiaohu. / "March 2008." / Adviser: Chan Hsiao Chang. / Source: Dissertation Abstracts International, Volume: 70-03, Section: B, page: 1516. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (p. 156-174). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Cheng, Baohui. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 206-221). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese.