Mini-dissertation submitted in partial compliance with the requirements for the Master’s Degree in Technology: Homoeopathy, Durban University of Technology, 2010. / The purpose of this study was to investigate the homoeopathic indications of the bark of the Strychnos henningsii tree, through a homoeopathic proving, and to subsequently compare these results to the documented traditional use of the crude substance. Methodology The study design took the form of a triple-blind placebo-controlled trial consisting of 32 participants who met defined inclusion criterion. These participants were randomly divided into four groups, each consisting of eight provers and supervised by one of four M. Tech Homoeopathy students. Fifty percent received placebo and fifty percent received verum. Neither the researcher nor the provers were aware of the nature of the proving substance as well as who received the placebo and who received the verum until the study was completed. The proving substance was administered in the 30CH potency, according to an ECH (European Committee of Homoeopathy) methodology. All provers were subjected to pre – and post -proving consultations in which case histories and physical examinations were performed. A pre-proving workshop was held for all provers and supervisors. Symptom collection was done by using information obtained from prover journals which was then collated, edited and translated into repertory language. By identifying broad areas of traditional use of Strychnos henningsii and relating these to rubrics derived from the proving of Strychnos henningsii 30 CH, a comparison was performed in order to evaluate the overlap between the homoeopathic indications and traditional use of the proving substance. Results After critical evaluation, it was found that whilst overlaps exist in the treatment of liver disease, nausea, dysmenorrhea, rheumatism, chest pain, malaria and dizziness, no overlap was found in the use of the homoeopathic remedy in snakebites. In addition the proving revealed symptoms that were not indicated in traditional use such as headaches, asthma, influenza, sinusitis and hayfever, as well as infections of the eye, ear, nose and throat. Conclusion Thus, upon comparison of the traditional uses of Strychnos henningsii to the symptoms produced in the proving of Strychnos henningsii 30CH, revealed that similarities pertaining mainly to the gastro-intestinal system, female gynaecological tract and rheumatic complaints exist. However, the proving elicited many new symptoms that are purely homoeopathic, these included head, mind, sleep, dream, nose, ear, chest and respiratory symptoms. Furthermore, it is hoped that further provings of this substance at different potencies would contribute further to the materia medica of the substance.

Dissertation submitted in partial compliance with the requirements of the Master’s Degree in Technology: Homoeopathy, Durban University of Technology, 2010. / The homoeopathic drug proving of Strychnos henningsii 30CH took the form of a mixed-method triple-blind, placebo-controlled study. The purpose of the study was to compare the results of the triple-blind homoeopathic drug proving with the toxicology of the crude substance. Methodology Thirty-two provers were selected and randomly divided into four equal groups of 8 provers, with each group supervised by one of four M.Tech.Hom student researchers. Fifty percent of the subjects (16 or the 32) received placebo in a random manner. Provers recorded their state in journals for one week prior to commencing the verum/ placebo powders. Data was extracted from journals and combined with case histories, physical examinations to compile the proving profile. The data derived from journals and case histories were edited and collated and thereafter reformatted and classified according to standard materia medica and repertory conventions. This constituted the homoeopathic remedy picture which was then compared to the toxicity of the major chemical constituents of Strychnos henningsii by qualitative methods. Results Provers produced symptoms on the mental, physical and emotional levels. There was a distinct similarity between the toxicology of Strychnos henningsii in its iii crude form, and a majority of the symptomatology obtained during the proving. The comparison of Strychnos henningsii proving symptoms and that of the crude substance was demonstrated by the proving symptoms showing similarity with the chemical constituents of the bark. The bark contained alkaloids which demonstrated similar symptoms in poisonings as described by the provers. The alkaloids found in the Strychnos henningsii bark were strychnine, diaboline, holstiine, strychnochromine and guianensine. Conclusions This homeopathic proving of Strychnos henningsii allowed for successful comparison between the alkaloids contained in the bark and the proving symptomatology. Notwithstanding the successful comparison and noted levels of overlap, it was observed that prior knowledge of homeopathy was beneficial to the provers. Furthermore, the researcher argues that the triple blind method employed is effective, but may hinder the researcher during analysis and that it is important that toxicological information about any substance should be obtained before a proving commences.

L'objectif de ce travail était d'accéder au squelette des alcaloïdes de type Aspidosperma et Strychnos à partir d'arylcyclohexa-2,5-diènes. Ces derniers sont d'abord synthétisés par réaction de Birch alkylante, puis ont été désymétrisés dans un premier temps par des réactions de Michael. Cette réaction fournit la cétone de Büchi, le noyau tétracyclique des alcaloïdes Aspidosperma en seulement en 6 étapes et un rendement global de 17%. Dans un second temps, la réaction d'amination oxydante catalysée par des métaux (Pd, Cu) a été développée. Cette réaction a permis un accès rapide au squelette pentacyclique d’aza-aspidospermanes et au squelette tétracycliques des alcaloïdes de type Strychnos. En parallèle, nous avons décrit une approche vers le squelette pentacyclique de la mossambine et la strychnine. / The aim of this work was to access the skeleton of the Aspidosperma and the Strychnos alkaloids using arylcyclohexa-2,5-dienes as common synthetic precursors. Initially, these arylcyclohexadienes were synthesized through Birch reductive alkylation reactions. The desymmetrization of these cyclohexadienes was developed via the Michael addition reaction, providing the Büchi ketone, the tetracyclic core of Aspidosperma alkaloids, in only 6 steps and 17% overall yield. On the other hand, we described the oxidative amination reaction catalyzed by metals (Pd, Cu). The palladium oxidative amination reaction allowed a fast access to the pentacyclic framework of aza-aspidospermanes and the tetracyclic framework of the strychnos. In parallel, we have described an approach toward the pentacyclic skeleton of mossambine and strychnine.

All Strychnos and Aspidosperma alkaloids possess a core pyrrolo[2,3-d]carbazole ABCE tetracycle. In order to develop an efficient and divergent methodology for the synthesis of Strychnos alkaloids, a streamlined synthetic sequence to the ABCE tetracycle has been developed. It features a Mitsunobu activation of an N-hydroxyethyl gramine intermediate and subsequent intramolecular aza-Baylis-Hillman reaction. This method was first applied in the total synthesis of (±)-alstolucine B. Additional key steps in the synthesis included (1) chemoselective intermolecular and intramolecular Michael additions and (2) a Swern indoline oxidation. The second application of this method was in the first total synthesis of (-)-melotenine A, a novel rearranged Aspidosperma alkaloid with potent biological activity. Additional key steps in the synthesis included (1) a Piers annulation of a vinyl iodide and a methyl ketone to prepare the D ring and (2) a site-selective intermolecular vinylogous aldol reaction / Chemistry

Submitted in fulfillment of the requirements of the Degree of Doctor of Technology: Homoeopathy, Durban University of Technology, 2011. / Aim This study sought to appraise homoeopathic proving methodology as a bridge between the indigenous and rationalist-scientific understandings of medicinal plants through a detailed exploration of the relationships existing between data derived from respective paradigmatic explorations of a single African traditional medicinal plant, Strychnos henningsii [Red bitterberry]. Methods The data derived from the implementation of a triple-blind, placebo-controlled homoeopathic proving methodology, on 32 healthy human subjects (50 percent placebo), using the bark of Strychnos henningsii in the 30CH potency, were evaluated for internal consistency and coherence, and subsequently compared to data derived from a phytochemical analysis of the crude bark sample, and translated data derived from semi-structured mothertongue interviews of eight Zulu traditional healers. The proving data took the form of subjective journal data and the results of four objective blood measures of erythrocyte sedimentation rate (ESR), redand white blood cell indices, and liver functions. The subjective data were evaluated in terms of defined inclusion criteria and presented in standard materia medica and repertory formats, and tabulations of objective data were subjected to independent statistical analysis, using repeated-measures ANOVA and profile plots. The crude bark sample was analysed in terms of the presence of strychnine and other indole alkaloids, using highperformance liquid chromatography-mass spectrometry, and interview data related to the indigenous understanding and application of Strychnos henningsii within the traditional African medical paradigm, were audiovisually recorded, collaboratively translated, and independently verified. ABSTRACT iii Qualitative data processing and analysis was effected with the aid of NVivo® software, and a range of comparative analyses were effected with the aid of Radar® homoeopathic software, materia medica references and the Mappa Mundi elemental theory model. Results The proving yielded 581 subjective symptoms, covering a broad range of physical and mental disease manifestations, and nine statistically-significant treatment effects within the objective data set. These included elevation of ESR and changes in two red blood cell indices, four white blood cell indices and two liver function indices. The two proving data sets were demonstrated to show high levels of correlation, although these correlations were not demonstrable for all provers. The phytochemical analysis confirmed the presence of between two and five strychnine-related compounds (excluding strychnine itself), and the field interview data served to confirm all except two documented traditions of use, as well as identifying a number of novel indications and application of Strychnos henningsii bark. The comparative analyses demonstrated the integrity of homoeopathic proving methodology as a mode of scientific investigation, and significant and widespread overlaps of proving symptomatology with both the pharmacology and toxicology of strychnine, and the physical and metaphysical understanding and application within the traditional African medical paradigm. Conclusions Homoeopathic proving methodology was discussed in terms of the evident degree of overlap with the indigenous and rationalist-scientific paradigms, and the incomplete nature of the homoeopathic ‘totality’. A number of recommendations were made for future cross-paradigmatic research. / Durban University of Technology. Postgraduate Development and Support Directorate.

Submitted by Marcela Carvalho (marcelaalfaia@hotmail.com) on 2016-09-02T13:46:27Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação Hector Henrique Ferreira K..pdf: 10781404 bytes, checksum: b77c916692bb09c590eddb00b5454b78 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-09-15T16:03:29Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação Hector Henrique Ferreira K..pdf: 10781404 bytes, checksum: b77c916692bb09c590eddb00b5454b78 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2016-09-15T16:05:07Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação Hector Henrique Ferreira K..pdf: 10781404 bytes, checksum: b77c916692bb09c590eddb00b5454b78 (MD5) / Made available in DSpace on 2016-09-15T16:05:07Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Dissertação Hector Henrique Ferreira K..pdf: 10781404 bytes, checksum: b77c916692bb09c590eddb00b5454b78 (MD5) Previous issue date: 2011-04-08 / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / Endophytic fungi are a promising source of bioactive molecules that may be used in the treatment of diseases, it is estimated that only 16% of species known, and which are known only 5% of all species in the world. In this work we isolated 58 strains of endophytic fungi from the hosts Strychnos cf. toxifera and Mauritia flexuosa, of which 35 strains are from the genus Penicillium, all were grown on a small scale and their extracts tested for their anticancer activity front the lines HCT-8, HL-60, MB-435 and SF-295, besides being tested for their antioxidant and antiacetilcolinesterase activities. We selected three strains (two from Penicillium and one of Gliocladium) of its active extracts were isolated 15 substances, the alkaloids glandicolin B, cyclo-(glycyl-L-tyrosyl) 4,4-dimethylallyl ether and the phenolic compound α-naphthol showed antimicrobial activity against several strains of pathogenic bacteria, the latter being first reported as a natural product. The phytochemical study of the roots from Mauritia flexuosa gave 10, including the provisory new compound 3-epi-20,21-diidroxithurberogenin. Flavonoids were isolated and attributed as being responsible for the antioxidant activity of the methanol extract of M. flexuosa. Cultivated strains of Penicillium were selected from 23 different EtOAc extracts had their chemical profiles compared by direct insertion into the mass spectrometer, a few selected ions were subjected to MS / MS experiments , was proposed the presence of the anthraquinone questinol and the macrocycle brefeldin A, the data were compared with those obtained from the host Strychnos cf. toxifera, and the strain STSP C2.3/1-2c that showed a profile very similar to that of their host, the data were statistically treated by five different methods of multivariate analysis (Average of the Links, Link Complete, Simple Connection, and Centroid Ward), they all discussed. / Fungos endofíticos são uma fonte promissora de moléculas bioativas que possam vir a ser utilizadas no tratamento de doenças, estima-se que apenas 16% das espécies de fungos conhecidas, e que são conhecidas apenas 5% de todas as espécies do mundo. Neste trabalho foram isolados 58 linhagens de fungos endofíticos das hospedeiras Strychnos cf. toxifera e Mauritia flexuosa, destas sendo 35 linhagens do gênero Penicillium, todas foram cultivadas em pequena escala e seus respectivos extratos testados quanto suas atividades anticâncer frente as linhagens HCT-8 (cólon-humano), HL-60 (leucemia humano), MB-435 (mama humano) e SF- 295 (glioblastoma humano), além de serem testados quanto suas atividades antiacetilcolinesterase e antioxidante. Foram selecionadas três linhagens (duas de Penicillium e uma de Gliocladium) de seus extratos ativos foram isoladas 15 substâncias, destas os alcalóides glandicolina B, ciclo-(Glicil-L-tirosil) 4,4-dimetilalil éter e o composto fenólico β-naftol apresentaram atividade antimicrobiana frente diversas linhagens de bactérias patógenas, este último sendo relatado pela primeira vez como um produto natural. Foi realizado o estudo fitoquímico das raízes de Mauritia flexuosa aonde foram isoladas 10 substâncias, sendo o triterpeno 3-epi-20,21-diidroxithurberogenina de estrutura provisória inédito na literatura. Flavonóides isolados foram atribuídos como sendo os responsáveis pela atividade antioxidante do extrato metanólico de M. flexuosa. Das linhagens de Penicillium cultivadas foram selecionadas 23 diferentes extratos do meio em AcOEt que tiveram seus perfis químicos comparados por inserção direta em espectrômetro de massas, alguns íons selecionados foram submetidos a experimetos de MS/MS de modo que se propôs a presença da antraquinona questinol e do macrocíclo brefeldina A, os dados foram comparados com os obtidos da hospedeira Strychnos cf. toxifera, sendo a linhagem Stsp C2.3/1-2c a que apresentou um perfil muito semelhante ao de sua hospedeira, os dados foram tratados estatisticamente por cinco métodos de análise multivariada (Média das Ligações, Ligação Completa, Ligação Simples, Centróide e Ward), todos eles discutidos.

Dissertation submitted in partial compliance with the requirements of the Master’s Degree in Technology: Homoeopathy, Durban University of Technology, 2011. / The purpose of this study was to investigate the relationship between the understanding and utilization of Strychnos henningsii (umqalothi, Red bitterberry) by Zulu traditional healers and the signs and symptoms induced by the thirtieth centesimal potency (30CH) homoeopathic dilution of the crude substance in a previously conducted triple-blind placebo-controlled homoeopathic proving. Methodology The study was carried out in four dispersed areas of KZN (Harding, Durban, Weenen and Melmoth). From each area one isangoma and one inyanga were interviewed, resulting in eight interviews. All visits were conducted by the researcher, who acted as principal communicator and translator, and his supervisor, who assisted him by doing live video recording of all interviews. The methodology employed was that of qualitative interviewing using semi-structured interviews. Each video was transcribed into Zulu text and subsequently translated to English text by the researcher and his supervisor. The data obtained from the interviews was then compared to data obtained from the previously conducted homoeopathic proving of Strychnos henningsii 30CH in order to evaluate the overlap between the traditional and the homoeopathic approach to utilisation of the plant. Results After comparison, it was found that there was an overlap in the gastro-intestinal system, cardio-vascular system, respiratory system and female/male genito-urinary system and in some mental symptoms. v However, there were no overlaps found in traditional usage of the plant as an antisnake venom, and in the proving symptoms related to scalp, hair, eyes, ear, nose, face, mouth, teeth and throat. Conclusion After comparison between the understanding and utilization of Strychnos henningsii by Zulu traditional healers and the signs and symptoms induced by the proving of Strychnos henningssi 30CH, it was concluded that while there are certain overlaps, the homoeopathic proving produced a wider range of symptoms which may either serve to extend the traditional use, or overlap with existing traditional use not exposed within the scope of this study. Interviews with a greater number of traditional healers in a wider geographic area may reveal a closer correlation between homoeopathic proving symptoms and patterns of use by traditional healers.

Univ., Diss.--Hannover, 2002.

The aim of this study was to isolate and characterize antifungal compounds from the most active medicinal plant species that could be used to address secondary infection problems in immunocompromised patients. An ethnobotanical study was conducted and 45 medicinal plant species used traditionally to treat candidiasis and related infections in HIV/AIDS patients were identified and documented. The most popular plant species used included Acacia caffra, Clerodendrum glabrum, Croton gratissimus, Elaeodendron transvaalense, Faurea saligna, Hippocratea longipetiolata, Osyris lanceolata, Richardia brasiliensis, Schkuhria pinnata, Schotia brachypetala, Spilanthes acmella, Strychnos potatorum, Vangueria infausta subsp. infausta and Withania somnifera. The plant parts used in the therapeutic preparations were roots (26.7%), bark (22.2%), and a combination of roots and bark (17.7%). Decoctions (44.4%), infusions (20%) and macerations (17.7%) were used. Most of the herbal remedies were administered orally. Chemical profiles of the plant species were established by using thin layer chromatography. Leaf extracts of these plant species were tested for antimicrobial activity against two common pathogenic fungal species in humans (Candida albicans and Cryptococcus neoformans) and four nosocomial bacteria (Staphylococcus aureus, Enterococcus faecalis, Escherichia coli and Pseudomonas aeruginosa) using a two-fold serial microdilution method and bioautography. All plant species investigated had some degree of antimicrobial activity against the test microorganisms. The hexane and the acetone extracts of Clerodendrum glabrum, Hippocratea longipetiolata, Schkuhria pinnata and Withania somnifera were the most active with MIC values ranging from 0.06 to 0.08 mg/ml. The most susceptible pathogen to the test samples was C. neoformans while C. albicans was resistant to most of the plant extracts. The water extracts of Withania somnifera and Hippocratea longipetiolata (14%) had MIC < 1 mg/ml against C. albicans. C. neoformans was susceptible to nine water plant extracts (64%) with MIC < 1 mg/ml and the promising activity was observed in Hippocratea longipetiolata and Faurea saligna extracts with MIC values of 0.16 and 0.31 mg/ml respectively. The hexane extract of C. glabrum was the most active against C. albicans with an MIC value of 0.06 mg/ml and total activity of 550 ml/g. In the bioautography, most plant extracts tested had few active compounds, others had no active components at all and this may be attributed to the disruption of synergism by the thin layer chromatography. C. glabrum had eight active antifungal compounds on bioautograms and most of these components were observed in the EMW solvent system. Based on this and its wide distribution in rural areas, C. glabrum was chosen for further study. The antioxidant activity and possible immune boosting potential of the species were determined using 1, 1-diphenyl-2-picrylhydrazyl radical (DPPH), 2, 2’ azinobis-(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) and ferric reducing antioxidant power (FRAP) assays. In the DPPH qualitative assay, the aqueous plant extracts had several prominent antioxidant components than the organic plant extracts. The aqueous plant extracts which had the most prominent antioxidant activity were F. saligna with 8 compounds, followed by E. transvaalense, H. longipetiolata O. lanceolata, R. brasiliensis and S.brachypetala, with five compounds each and their Rf values ranged from 0;06 to 0.94. This appears to validate the ethnomedicinal use of the plant species to some extent because decoction is the most common method used in the preparation of the remedy by the traditional healers. With regard to the organic plant extracts, only one plant extract, F. saligna had two prominent antioxidant components at Rf values 0.81 and 0.88. A third of the plant species had a high level of free radical scavenging activities in the DPPH, ABTS and FRAP assays. However, all plant extracts had lower antioxidant activity than the positive control (Trolox) used. The selected plant species were also evaluated for their in vitro toxicity against the Vero monkey kidney cell line using 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. The acetone plant extracts of O. lanceolata, S. acmella, S. pinnata and S. brachypetala had high cytotoxic activity against Vero cells with IC50 values of 13.7±0, 19.9±0.001, 21.6±0.001 and 28.34±0.001 μg/ml respectively. However, their IC50 values were higher than that of the positive control, doxorubicin (IC50 = 9.9±0 μg/ml). The rest of the acetone plant extracts (64%) had moderate cytotoxic activity (30 < IC50<100 μg/ml). The aqueous plant extracts were relatively non-toxic to the Vero cells with IC50 values ranging from 137 to > 500 µg/ml. This supports the use of aqueous extracts in the traditional medicine. However, their low selectivity index values ranging from 0.26 to 1.68 suggest that the plant extracts are probably suitable for external use only. Fractionation of the hexane extract of the leaves of C. glabrum by chromatographic techniques yielded six fractions of which fractions C and D had significant antifungal activity (average MIC value = 0.1 mg/ml) against C. albicans and C. neoformans. From these fractions, one new triterpenoid, 3-(1-oxobutyl)-11α-hydroxytaraxast-20(30)-ene-24,28-dioic acid (clerodendrumic acid) (1) was isolated along with known heptadecanoic acid (2). C. albicans was relatively insensitive to clerodendrumic acid (1) (MIC value = 125 µg/mL) and was resistant to heptadecanoic acid (2) (MIC value = 188 µg/ml). Compounds 1 and 2 were non-toxic against monkey kidney Vero cells in vitro with IC50 values of 202.6 and 108.4 µg/ml respectively. Due to its low antifungal activity, the novel compound clerodendrumic acid (1) is not a viable candidate for drug development which could be used to combat candidiasis and related fungal infections. However, due to its relative safety, it may possibly be used as a lead compound to produce new chemically modified active derivatives or could be used together with known antibiotics to mitigate their undesirable side effects. To the best of our knowledge, the isolation of a novel, clerodendrumic acid (1) and a known heptadecanoic acid (2) compounds from leaf extracts of C. glabrum is reported herein for the first time. The results obtained from this study generally substantiate the rationale behind the use of the selected plant species in the traditional medicine to treat candidiasis and related infections to some extent. This study showed the potential of studying traditional medicine in the search for effective plant extracts or new lead compounds that could be developed into drugs for combating microbial infections among the rural poor people. / Thesis (PhD)--University of Pretoria, 2013. / gm2013 / Paraclinical Sciences / Unrestricted