Venereal diseases (VDs) are infections that are mainly transmitted through sexual intercourse and amongst these are gonorrhoea, syphilis, chlamydia and trichomoniasis. Gonorrhoea is the most commonly known VD and the widest spread contagious infection in the world. Out of 448 million cases of curable venereal infections, gonorrhoea represents 88 million cases and the rest are syphilis, chlamydia and trichomoniasis. Gonorrhoea has recently been rated as in the emergent multidrug resistance phase. Venereal diseases are amongst the major diseases ravaging many rural communities. People infected with these diseases are considered a disgrace in the community. Indigenous populations, for example the Vha-Venda people tend to use medicinal plants to treat these infectious diseases rather than using western medicines. Vha-Venda people have depended on medicinal plants for their health and survival for millenia. In order to validate and give scientific credence to the use of medicinal plants by the Vha-Venda people for venereal diseases, several pharmacological assays were carried out. The study was aimed at evaluating the; antimicrobial, anti-inflammatory activities, HIV-type 1 reverse transcriptase (RT) inhibition properties and to determine phenolic contents as well as evaluating the mutagenic properties of, 12 medicinal plants used by the Vha-Venda people against venereal and related diseases. An attempt was also made toward isolating and identification of the most active compounds from some extracts that were active against Neisseria gonorrhoeae. Twelve medicinal plants and various plant parts, Adansonia digitata (bark), Acacia karroo (bark), Aloe chabaudii (roots), Bolusanthus speciosus (leaves, bark and stem), Ekebergia capensis (leaves and bark), Elephantorrhiza burkei (roots), Grewia occidentalis (roots), Osyris lanceolata (roots), Pappea capensis (leaves), Peltophorum africanum (bark), Pterocarpus angolensis (leaves and bark) and Ximenia caffra (leaves and roots) were evaluated for their antimicrobial properties against two Gram-positive (Bacillus subtilis and Staphylococcus aureus), three Gram-negative (Neisseria gonorrhoeae, Escherichia coli and Klebsiella pneumonia) bacteria and the fungus Candida albicans. The plant materials were extracted with petroleum ether (PE), dichloromethane (DCM), 80% ethanol (EtOH) and water. Methanol was used for extracting materials for phenolic contents and HIV-1RT assays. The Disc diffusion method was used to determine gonococcal percentage inhibition and a microdilution assay was used to determine minimum inhibition concentration (MIC) and minimum fungicidal concentrations (MFC). Bolusanthus speciosus and X. caffra extracts exhibited the best antigonococcal, antifungal and antibacterial activities whilst A. digitata and A. chabaudii showed poor activities. The medicinal plants were also evaluated for cyclooxygenase (COX-1 and -2) and HIV-1 reverse transcriptase inhibition activity. The DCM and PE extracts of A. digitata bark, B. speciosus bark, P. angolensis bark and P. capensis leaves showed good anti-inflammatory activity against both COX-1 and COX-2. Methanol and water extracts of B. speciosus stems, P. africanum bark, P. angolensis leaves and P. capensis leaves exhibited good anti-HIV-1 RT activity. A. chabaudii roots, E. capensis bark and O. lanceolata roots showed low HIV-1 RT percentage inhibition. Phytochemical analysis using spectrophotometric methods revealed the presence of a variety of phenolic compounds in all the plant extracts including total phenolics, flavonoids, gallotannins and condensed tannins. High levels of total phenolics, flavonoids, gallotannins and condensed tannins were detected in X. caffra. Low amounts of flavonoids, gallotannins and condensed tannins were detected in B. speciosus. The Ames test using Salmonella typhimurium tester strain TA98 with and without S9 metabolic activation revealed that all plant extracts were non-mutagenic toward S. typhimurium strains TA98 without metabolic activation. However, E. burkei roots and E. capensis bark showed mutagenic effects toward TA98 after metabolic activation. Therefore, these two plants need to be used with caution, however more studies are required to confirm this result. Good antimicrobial activity observed in X. caffra leaves prompted an attempt to isolate active compounds. A pure compound from X. caffra leaves exhibited moderate activity (63%) against N. gonorrhoeae. However, the structure of the compound has as yet to be ratified. Pharmacological activity of the twelve medicinal plants used by Vha-Venda people against venereal and related diseases were validated in this study. The results obtained in this study give credence to the use of some of these plants. This study has further confirmed the need for screening these medicinal plants for more pharmacological activities. These plants may offer a new source of chemicals for the effective treatment of venereal and related diseases. / Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2012.

The Orchidaceae makes up the largest and most diverse family of flowering plants. Orchids are popular, often expensive ornamentals, with a broad range of ethnobotanical applications. There is very limited documented information on South African medicinal orchid species; no formal pharmacopoeia outlining ethnobotanical uses; and ethnobotanical and distribution records are either scarce or inconsistent and plant populations are becoming gradually smaller. There have been significant developments in medicinal orchid research worldwide with medicinal use and corresponding pharmacological and phytochemical properties being extensively investigated. It is evident from the literature that there is no pharmacological research on South African medicinal orchids; hence the need to explore biological activity and chemical composition of South African medicinal orchid species. The ethnobotanical approach used to select the orchid species for pharmacological and phytochemical research elsewhere, yielded valuable biological compounds. Thus, a similar approach was applied to South African medicinal orchids. There are approximately 20 000 species and 796 genera of orchids distributed across the world. In southern Africa, orchids are widely represented with 55 genera and 494 species. Approximately 75% are endemic to this region. As part of the current investigation a review of available ethnobotanical literature on South African medicinal orchids was prepared. The review revealed that an estimated 49 indigenous orchid species from 20 orchid genera are currently being informally traded and used in South African traditional medicine. They are used primarily for medicinal and cultural purposes, especially by the Zulu community in South Africa. Medicinal uses of orchid species include: treatment of inflammatory, intestinal, neurological and reproductive disorders and emetics are used to cause emesis. Non-medicinal uses of orchid species include: love, fertility, protective and lethal charms. Based on their ethnobotanical uses and endemism, South African orchids were considered to be one of the untapped sources of bioactive compounds that needed to be researched. The current investigation addressed the broader aims of medicinal plant research by determining the efficacy, safety and chemical profile of seven indigenous orchid species used in South African traditional medicine and practices. The biological and toxic effects of orchid plant extracts were assessed using established pharmacological bioassays. The phytochemical evaluation of the seven orchid plant extracts provided insight into the classes of chemical compounds present and their possible role in the observed biological activities. The potential of plant extracts from seven orchid species used in South African traditional medicine, as sources of natural bioactive products, are discussed. The current investigation determined the biological activity and chemical profile of seven orchid species commonly traded in KwaZulu-Natal herbal markets: Ansellia africana Lindl., Bulbophyllum scaberulum (Rolfe) Bolus, Cyrtorchis arcuata (Lindl.) Schltr., Eulophia hereroensis Schltr., Eulophia petersii (Rchb.f.) Rchb.f., Polystachya pubescens (Lindl.) Rchb.f. and Tridactyle tridentata (Harv.) Schltr. Well established in vitro micro-dilution bioassays were used to determine the antibacterial, antifungal, anthelmintic activities of crude orchid extracts. A minimum inhibitory and/or lethal effect of organic and aqueous crude orchid extracts was observed against Bacillus subtilis, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Candida albicans and Caenorhabditis elegans. Tridactyle tridentata aqueous root extract produced the most effective antibacterial activity against S. aureus (0.049 mg/ml). All T. tridentata organic root extracts produced significant inhibitory activities against B. subtilis and S. aureus. Eulophia petersii DCM pseudobulb extracts significantly inhibited all bacterial strains tested (0.39 mg/ml against S. aureus and 0.78 mg/ml against B. subtilis, E. coli, and K. pneumoniae). Eulophia hereroensis 80% EtOH root extract was the only other extract to exhibit significant inhibitory effects against K. pneumoniae (0.65 mg/ml). After 48 h C. albicans was most susceptible to P. pubescens aqueous pseudobulb extract (0.0816 mg/ml). Eulophia petersii DCM pseudobulb extract however, exhibited significant activity against C. albicans (0.65 mg/ml) over 72 h. Cyrtorchis arcuata leaf and root extracts were the most effective anthelmintic extracts with MLCs of 0.041 mg/ml for 80% EtOH leaf and root extracts; 0.049 mg/ml for aqueous leaf extracts and 0.78 mg/ml for aqueous and DCM root extracts. Caenorhabditis elegans was most susceptible to all A. africana and T. tridentata organic root extracts. A similar significant effect was observed for all E. petersii organic pseudobulb extracts, DCM extracts and organic root extracts of B. scaberulum. Only the DCM tuber and root extracts of E. hereroensis exhibited lethal effects on C. elegans. All of the P. pubescens extracts showed poor anthelmintic activity. Similarly, in vitro enzyme based cyclooxygenase (COX) 1 and 2 and acetylcholinesterase (AChE) inhibitory bioassays, revealed significant inhibition of COX-1, COX-2 and AChE enzymes by crude organic and certain aqueous orchid extracts. Out of a total of 53 evaluated extracts, 21 and 13 extracts exhibited significant anti-inflammatory activity in the COX-1 and COX-2 assays respectively. The DCM tuber extract of E. hereroensis was the only extract to significantly inhibit both COX enzymes, 100.02±0.11% and 87.97±8.38% respectively. All B. scaberulum root extracts (DCM, EtOH and water) exhibited COX-2 selective inhibitory activity (100.06±0.01, 93.31±2.33 and 58.09±3.25%). Overall, the DCM root extract of A. africana was found to be the most potent extract (EC50 0.25±0.10 mg/ml). The 80% EtOH root extract of B. scaberulum was the most potent in the COX-2 assay (EC50 0.44±0.32 mg/ml). Generally the root extracts exhibited greater AChE inhibitory activity; where the most active extract was B. scaberulum DCM root extract (EC50 0.02±0.00 mg/ml). All aqueous extracts, except that of A. africana roots and B. scaberulum pseudobulbs, showed poor or no COX-1 and COX-2 inhibition. The antioxidant capacity of crude orchid extracts was determined using: hydrogen atom transfer (HAT) (β-carotene/linoleic acid assay) and single electron transfer (SET) (2,2‟-diphenylpicrylhydrazyl (DPPH) free radical scavenging assay and ferric reducing antioxidant power (FRAP) assay) reaction-based assays. Potent antioxidant effects were observed for certain crude methanolic orchid extracts. Generally, there was a dose-dependent change in radical scavenging activities of crude extracts from which EC50 values were determined. The root extracts of all species, except that of E. petersii, had consistently more effective radical scavenging activity than that of other plant parts within each species. The pseudobulb extract of E. petersii, was the most potent extract (EC50 1.32±0.86 mg/ml). In the β-carotene-linoleic acid assay, based on the oxidation rate ratio (ORR), the leaf extract of T. tridentata and the root extracts of C. arcuata and E. hereroensis exhibited the best antioxidant effects (0.02, 0.023 and -0.15 respectively). Similarly, the average antioxidant activity (%ANT) of these samples was greater than that of BHT (95.88±6.90%) and all other samples. Bulbophyllum scaberulum leaf, pseudobulb and root extracts, E. petersii pseudobulb extract and T. tridentata root extract also exhibited a greater capacity to prevent β-carotene oxidation when compared to BHT. All crude orchid extracts tested demonstrated a general dose-dependent response in the ferric reducing power assay. The reducing power of ascorbic acid (0.08 mM) and BHT (0.05 mM), as measured as absorbance, was 1.12±0.12 and 0.73±0.08 respectively. At 6.25 mg/ml, A. africana root and E. petersii pseudobulb extracts were the most effective in reducing power activity. The short-term bacterial reverse mutation Ames Salmonella/microsome mutagenicity (ASMM) assay, which makes use of mutant histidine-dependent Salmonella typhimurium strains, was used to determine the mutagenicity and toxicity of crude orchid extracts. In the presence of a mutagen S. typhimurium TA98 strain detects frameshift events while the TA100 and TA102 strains detect base-pair substitutions. In the absence of metabolic activation, mutagenic extracts were observed against the TA98 strain only. All A. africana DCM leaf and stem extracts tested, the DCM root extract (0.5, 0.05 mg/ml) and EtOH leaf, stem and root extracts at 5 mg/ml exhibited mutagenic effects. The EtOH root extracts (5, 0.5 mg/ml) of B. scaberulum exhibited mutagenic indices (MI) comparable to that of 4NQO (17.00 and 13.00, respectively). Eulophia petersii PE pseudobulb extract demonstrated mutagenic potential at 5 mg/ml. The ethanolic root extracts of T. tridentata showed mutagenic effects at 5 and 0.5 mg/ml. The mutagenicity index (MI) with metabolic activation (S9) was determined using only the TA98 strain; where no mutagenic effects were observed. In the phytochemical evaluation of crude methanol orchid extracts, the Folin-Ciocalteu assay for total phenolics, butanol-HCl assay for condensed tannins, rhodanine assay for gallotannins and vanillin assay for flavonoids revealed a quantitative chemical profile of the tested samples. The correlation between observed biological effects and chemical compounds present was found to be generally significant. The significant antimicrobial, anthelmintic, anti-inflammatory and antioxidant activity of E. petersii pseudobulb extracts and E. hereroensis tuber and root extracts may be attributed to their high total phenolic content. Alternatively, the significant levels of gallotannin content in E. hereroensis may have contributed to the bioactivity. The flavonoid content of B. scaberulum and T. tridentata may explain the potent activity observed in the anti-inflammatory, antioxidant and acetylcholinesterase inhibitory assays; while the flavonoid content C. arcuata may have contributed to the potent anthelmintic and antioxidant activities. The significantly higher levels of gallotannin content may explain the significant anti-inflammatory and anthelmintic activity of A. africana. A number of biologically active compounds have been isolated from certain Orchidaceae species around the world on the basis of their traditional medicinal uses. The traditional uses of these orchid species were scientifically validated. No pharmacological research has been previously conducted on South African medicinal orchids; therefore the current investigation has produced novel findings on the efficacy and safety of these orchid species and promotes the continued research of medicinal orchids in South Africa. / Thesis (Ph.D.)-University of KwaZulu-Natal, Pietermaritzburg, 2012.

Ethanol causes neurotoxicity via several mechanisms at different points in the cycle of dependence, including neuroinflammation and oxidative stress during ethanol exposure as well as excitotoxicity during ethanol withdrawal. The primary therapeutic implication is that ethanol-induced neurotoxicity requires multifunctional pharmacotherapies which reduce all mechanisms. Using an innovative pharmacological high throughput screening method on a large plant extract library we discovered flavonoids with alpha7 nicotinic acetylcholine receptor (nAChR) activity. In addition to their well-known anti-inflammatory and antioxidant properties, this novel activity means they can potentially reduce excitotoxicity and therefore makes them ideal for inhibition of ethanol-induced neurotoxicity. Rhamnetin, the candidate compound, was first found to inhibit lipopolysaccharide induced inflammation in immortalized BV2 microglia, in part, via alpha7 nAChRs. We then established an in vitro model of ethanol induced-neurotoxicity using organotypic hippocampal slice cultures which incorporated both neuroinflammatory and excitotoxic components. Neuroinflammation enhanced excitotoxicity under control conditions but the reverse was observed during ethanol withdrawal. Both mechanisms are important but their interaction is not simple. Finally, rhamnetin was evaluated in this model and found to reduce neuroinflammation and excitotoxicity associated with ethanol withdrawal. In conclusion, the studies herein provide strong evidence for alpha7 nAChRs selective flavonoids as potential pharmacotherapies for the treatment of ethanol-induced neurotoxicity and further implicate neuroinflammation, excitotoxicity, and their interaction as critical mechanisms in this pathology.

Marine invertebrates, in particular sponges, represent a source of a wide range of secondary metabolites, many of which have been attributed various defensive capabilities against environmental stress factors. In this thesis sponge-derived low-molecular peptide-like compounds and associated analogs are investigated for bioactivity and pharmacological targets. The compound bromobenzisoxazolone barettin (cyclo[(6-bromo-8-(6-bromo-benzioxazol -3(1H)-one)-8-hydroxy)tryptophan)]arginine) was isolated from the sponge Geodia barretti and its ability to inhibit larval settlement of the barnacle Balanus improvisus was determined. With an EC50 value of 15 nM, this compound’s antifouling effect was higher than those of the previously reported brominated dipeptides from Geodia barretti, i.e., barettin and 8,9-dihydrobarettin; moreover, this antifouling effect was demonstrated to be reversible. However, the compound lacked affinity for 5-HT1-7 receptors, whereas barettin possessed specific affinity to 5-HT2A, 5-HT2C and 5-HT4, while 8,9-dihydrobarettin interacted with 5-HT4. In an attempt to evaluate structure-activity relationships synthesized analogs with barettin and dipodazine scaffolds were investigated for antifouling activity. The analog benso[g]dipodazine, with an EC50 value of 34 nM, displayed the highest settlement inhibition. The studies of the structure-activity relationships of sponge-derived compounds were extended to cover analogs of agelasines and agelasimines originally isolated from sponges of the genus Agelas. Synthesized (+)-agelasine D and two structurally close analogs were investigated for cytotoxic and antibacterial activity. The profound cytotoxicity and broad spectrum antibacterial activity found prompted a further investigation of structure-activity relationships in 42 agelasine and agelasimine analogs and several characteristics that increased bioactivity were identified. In conclusion this work has produced new results regarding the potent bioactivity of compounds derived from the sponges Geodia barretti and Agelas spp. and increased SAR knowledge of the fouling inhibition, cytotoxicity and antimicrobial activity of these compounds.

Background This thesis investigated the efficacy and safety of Bacopa monnieri in improving memory in healthy Australians over the age of 55-years. A review of the literature showed that memory impairment and dementia are increasingly prevalent in the current demographic climate of an ageing population. As well as the pathological cognitive loss of neurodegenerative disease, many older persons are experiencing memory loss as part of the physiological process of ageing. Bacopa monnieri is a herbal medicine used since antiquity in the traditional Ayurvedic medical system of India for its cognitive enhancing effects. A number of pre-clinical and clinical studies support this traditional usage. Laboratory studies have demonstrated antioxidant and cholinergic actions in the brain as well as improved memory and cognitive performance in animal models. Human trials of Bacopa have also demonstrated improved memory performance. Some of these trials are limited by methodological flaws such as lack of blinding, small sample sizes, or use of outcome measurements which are not well validated. However, a small number of well designed human trials provide evidence for efficacy in cognitive and memory performance improvement. The current study was employed to extend on previous findings by assessing the efficacy and safety of Bacopa in the aged population specifically, as it is in this population that memory impairment becomes apparent. Aims 1. To assess the efficacy of Bacopa monnieri in improving memory in healthy Australians over the age of 55-years. 2. To assess whether the use of Bacopa is associated with side-effects Design A 12-week, randomised, double-blind, placebo-controlled, parallel group clinical trial. Participants Participants were self selected from the general population. They were aged 55-years or over at the commencement of the trial. Participants were without dementia, depression or other serious health conditions and did not use psychotropic medications. Intervention Participants were randomised to one of two treatment conditions, either a tableted extract of Bacopa monnieri called Bacomind™ (300mg/day, standardised to contain at least 40% bacosides), or an identical placebo. Participants attended three clinical evaluations: the first an initial screening session, the second a baseline evaluation of neuropsychological function and subjective memory performance at the commencement of the trial and the third, an end-of-trial outcome evaluation at 12-weeks, during which neuropsychological function and subjective memory performance were again assessed along with side-effects and study compliance. Primary Outcome Measures Rey Auditory Verbal Learning Test (AVLT), Rey-Osterrieth Complex Figure Test (CFT), Memory Complaint Questionnaire (MAC-Q), and Trail Making Test (TMT) Results From 136 people who elected to participate, 103 people met study entry criteria and 98 of these commenced the trial. Of these, 81 participants completed the trial and provided evaluable data for the end point analysis. Bacopa monnieri versus placebo significantly improved verbal learning as well as delayed recall as measured by the AVLT (p<.05). Though improvements were noted in the CFT, MAC-Q and TMT, there were no significant differences between placebo and active groups found for these tests. The Bacopa group reported a higher incidence of gastro-intestinal (GIT) side-effects than the placebo group, these predominantly being increased stool frequency, abdominal cramps and nausea. No other significant adverse effects were found. Conclusions A clinical trial was carried out to assess the effects of 12-weeks administration of Bacopa monnieri (300mg/day) on memory performance in people over the age of 55-years. Primary outcome measures were well validated neuropsychological tests that objectively measured verbal and visual memory and a memory complaint questionnaire that measured subjective memory complaints. The results demonstrated that Bacopa significantly improved memory acquisition and retention in older Australians. This concurs with findings from previous human and animal studies, as well as supports traditional Ayurvedic claims and uses. The beneficial effects on memory observed may be due to previously demonstrated antioxidant and cholinergic effects of the herb on the central nervous system. The use of Bacopa was associated with GIT side-effects, particularly increased bowel movements, nausea and abdominal cramping, findings infrequently reported previously. Possible explanations for these side-effects include GIT irritation by the saponin constituents of the herb, or cholinergic stimulation of autonomic and motor responses in the GIT, or a combination of both of these factors. The side-effects observed in the current study provide supportive evidence that Bacopa may increase cholinergic activity in humans. A worthwhile future extension of the current study would be to assess whether the finding of Bacopa’s efficacy for improving memory performance is replicable in populations with either mild cognitive impairment or early dementia.

Background This thesis investigated the efficacy and safety of Bacopa monnieri in improving memory in healthy Australians over the age of 55-years. A review of the literature showed that memory impairment and dementia are increasingly prevalent in the current demographic climate of an ageing population. As well as the pathological cognitive loss of neurodegenerative disease, many older persons are experiencing memory loss as part of the physiological process of ageing. Bacopa monnieri is a herbal medicine used since antiquity in the traditional Ayurvedic medical system of India for its cognitive enhancing effects. A number of pre-clinical and clinical studies support this traditional usage. Laboratory studies have demonstrated antioxidant and cholinergic actions in the brain as well as improved memory and cognitive performance in animal models. Human trials of Bacopa have also demonstrated improved memory performance. Some of these trials are limited by methodological flaws such as lack of blinding, small sample sizes, or use of outcome measurements which are not well validated. However, a small number of well designed human trials provide evidence for efficacy in cognitive and memory performance improvement. The current study was employed to extend on previous findings by assessing the efficacy and safety of Bacopa in the aged population specifically, as it is in this population that memory impairment becomes apparent. Aims 1. To assess the efficacy of Bacopa monnieri in improving memory in healthy Australians over the age of 55-years. 2. To assess whether the use of Bacopa is associated with side-effects Design A 12-week, randomised, double-blind, placebo-controlled, parallel group clinical trial. Participants Participants were self selected from the general population. They were aged 55-years or over at the commencement of the trial. Participants were without dementia, depression or other serious health conditions and did not use psychotropic medications. Intervention Participants were randomised to one of two treatment conditions, either a tableted extract of Bacopa monnieri called Bacomind™ (300mg/day, standardised to contain at least 40% bacosides), or an identical placebo. Participants attended three clinical evaluations: the first an initial screening session, the second a baseline evaluation of neuropsychological function and subjective memory performance at the commencement of the trial and the third, an end-of-trial outcome evaluation at 12-weeks, during which neuropsychological function and subjective memory performance were again assessed along with side-effects and study compliance. Primary Outcome Measures Rey Auditory Verbal Learning Test (AVLT), Rey-Osterrieth Complex Figure Test (CFT), Memory Complaint Questionnaire (MAC-Q), and Trail Making Test (TMT) Results From 136 people who elected to participate, 103 people met study entry criteria and 98 of these commenced the trial. Of these, 81 participants completed the trial and provided evaluable data for the end point analysis. Bacopa monnieri versus placebo significantly improved verbal learning as well as delayed recall as measured by the AVLT (p<.05). Though improvements were noted in the CFT, MAC-Q and TMT, there were no significant differences between placebo and active groups found for these tests. The Bacopa group reported a higher incidence of gastro-intestinal (GIT) side-effects than the placebo group, these predominantly being increased stool frequency, abdominal cramps and nausea. No other significant adverse effects were found. Conclusions A clinical trial was carried out to assess the effects of 12-weeks administration of Bacopa monnieri (300mg/day) on memory performance in people over the age of 55-years. Primary outcome measures were well validated neuropsychological tests that objectively measured verbal and visual memory and a memory complaint questionnaire that measured subjective memory complaints. The results demonstrated that Bacopa significantly improved memory acquisition and retention in older Australians. This concurs with findings from previous human and animal studies, as well as supports traditional Ayurvedic claims and uses. The beneficial effects on memory observed may be due to previously demonstrated antioxidant and cholinergic effects of the herb on the central nervous system. The use of Bacopa was associated with GIT side-effects, particularly increased bowel movements, nausea and abdominal cramping, findings infrequently reported previously. Possible explanations for these side-effects include GIT irritation by the saponin constituents of the herb, or cholinergic stimulation of autonomic and motor responses in the GIT, or a combination of both of these factors. The side-effects observed in the current study provide supportive evidence that Bacopa may increase cholinergic activity in humans. A worthwhile future extension of the current study would be to assess whether the finding of Bacopa’s efficacy for improving memory performance is replicable in populations with either mild cognitive impairment or early dementia.

Magister Pharmaceuticae - MPharm / 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. / South Africa

No presente trabalho, realizou-se o estudo químico da fração alcaloídica total de Duguetia lanceolata St. Hil. (Annonaceae), espécie proveniente do cerrado paulista, tendo-se obtido o perfil cromatográfico e a separação decomponentes da fração alcaloídica, que resultou na obtenção do alcaloide aporfínico majoritário N-acetilanonaína, isolado da espécie, pela primeira vez. No estudo botânico de folhas, foram descritas as características da morfologia externa e interna, tendo sido ilustradas por fotografias e fotomicrografias dos itens mais importantes para a diagnose da droga caracteres xeromórficos, como: consistência coriácea, cutícula espessa, escamas e tricomas tectores estrelares nas epidermes, presença de bainhas e grandes grupos de células esclerenquimáticas freqüentes, na nervura mediana e no pecíolo. Entre outros elementos de destaque encontram-se: a distribuição de drusas na epiderme e a presença de células oleíferas dispersas no mesofilo. A avaliação da atividade antiprotozoária mostrou, de forma geral, que frente ao Plasmodium falciparum, os alcalóides totais são mais ativos sobre a cepa resistente à cloroquina (K-1) (CE50:2,0&#181;g/mL) o que também foi observado para os mesmos componentes acetilados (CE50:3,0&#181;g/mL). Tanto o extrato etanólico, quanto os alcaloides totais (l00&#181;g/mL) da espécie, demonstraram elevados níveis de atividade frente às formas tripomastigotas de Tripanosoma cruzi, tendo apresentado percentual de morte de cerca de 100% e 66%, respectivamente. Este último, foi comparável ao benznidazol, fármaco usado como referência. Tais resultados são promissores tendo em vista que, os extratos não apresentaram citotoxicidade sobre as células de camundongos (RAW 264.7), até a maior concentração testada (120&#181;g/mL). No ensaio de citotoxicidade sobre Artemia salina, os extratos etanólico e alcaloídico foram ambos inativos (DL50>1000&#181;g/mL), em contraste com os alcalóides totais acetilados que demonstraram nível de toxicidade comparável ao do sulfato de atropina (DL50:867,60&#181;g/mL) utilizado como referência, no ensaio. / ln this work, some chemical, botanical and pharmacological aspects of the brazilian Duguetia lanceolate St. Hil (Annonaceae) were considered. The plant specimen was collected from the cerrado biome, at São Paulo, Brazil. The isoquinoline alkaloid fraction was extracted and then acetylated. After performed the chromatographic profile, the column fractionation led to the first isolation of the major aporphine N- acetyl-anonaine from this specie. Morphological and anatomical characters of the leaves were described and illustrated by photographies and photomicrographies. Some xeromorphic characters, typical from cerrado species, were recognized: coriaceous leaves, thick cuticle, scales, stellate non-glandular trichomes, sclerenchymatic vascular sheats and scattered sclerenchymatic cell groups in the median nervure and petiole. Other important features were observed: isolated druses of calcium oxalate in each epidermal cells and oil cells scattered in the mesophyll. Evaluation of the antiprotozoal activity showed that the total alkaloid fraction (EC50:2,0&#181;g/mL) and the same acetylated fraction (EC50:3,0&#181;g/mL), were more active against the chloroquine resistant strain (K-1) of Plasmodium falciparum. The total acetylated alkaloids and the ethanolic extract (l00&#181;g/mL) were highly active (0% of survival) against trypomastigotes of Tripanosoma cruzi. ln the same test, non acetylated alkaloids (l00&#181;g/mL) killed about 66% of the parasite forms, having an activity comparable to Benznidazole, the standard drug. Those results were promising, considering the low cytoxicity showed by the plant extracts (ethanol and total alkaloid) over mice macrophages RAW 264.7, at the maximum tested concentration (120 &#181;g/mL). The ethanol and total alkaloid extracts showed, also, low levels of citotoxicity (LD50>l000&#181;g/mL), when assayed against the Artemia salina while the acetylated alkaloids had a LD50 value (843,2 &#181;g/ml) comparable to the atropine sulphate.

Campomanesia phaea L, espécie da família Myrtaceae, popularmente denominada de \'cambuci\' foi estudada através de uma abordagem botânica, química e farmacológica. A planta foi coletada e é cultivada no Instituto de Agronomia da Estação Experimental de Ubatuba no litoral norte do Estado de São Paulo. O estudo morfo-anatômico das folhas foi realizado conjuntamente com uma triagem fitoquímica de seus constituintes químicos mais importantes e seus extratos foram ensaiados farmacológica e microbiologicamente. O ensaio de toxicidade aguda foi realizado em camundongos e a avaliação da atividade antimicrobiana foi realizada com o extrato liofilizado contra bactérias Staphylococcus aureus (ATCC 6538) e Pseudomonas aeruginosa (ATCC 9027), em levedura, Candida albicans (ATCC 10231), e bolor, Aspergillus niger (ATCC 16404). O óleo volátil presente nas folhas da espécie, foi extraído por hidrodestilação em aparelho de Clevenger. O óleo bruto obtido, foi submetido à análise para identificação de seus componentes por cromatografia em camada delgada preparativa, cromatografia a gás e cromatografia a gás acoplada à espectrometria de massa (CG/EM) com banco de dados. Dentre 38 componentes reconhecidos, 34 foram identificados. A planta é rica em óleo essencial contendo linalol (11,1%), componente de grande valor comercial para a indústria de cosméticos e na indústria farmacêutica, óxido de cariofileno (11,8%), beta-cariofileno (6,3%), beta-selineno (6,9%) e alfa-cadinol (7,5%). / One of the most important species of Myrtaceae, commonly known in the Atlantic coast shore of São Paulo State, is Campomanesia phaea L, \'cambuci\'. It is widespread near the seashore, utilized not only in folklore medicine, due to a high tanin content of its stem bark, but also due to the exotic fruits that offers special flavor in alcoholic beverages. Botanical, chemical and farmacological approach has been performed to study the plant. Acute toxicity test has been perform in mice and the antimicrobial studies were performed against Staphylococcus aureus (ATCC 6538), Pseudomonas Aeruginosa (ATCC 9027), Candida albicans (ATCC 10231), and Aspergillus niger (ATCC 16404). The composition of the water-destilled volatile oil in the leaves has been analysed using gas chromatography, GC/MS and TLC . Among 38 compounds recorded by GC, GC-MS and TLC, 34 components were identified. The volatile oil was found to be rich in linalool (11,1%), important substance that can be utilized in pharmacy and cosmetics, caryophyllene oxyde (11,8%), beta-caryophyllene (6,3%), beta-selinene (6,9%), and alfa-cadinol (7,5%).

Acanthospermum australe (Loefl.) O. Kuntze, conhecido popularmente no Brasil como carrapichinho pertence à família Asteraceae e é utilizado na medicina popular como hepatoprotetora, diaforética, antiblenorrágica, antimalárica, entre outras funções. O objetivo do presente trabalho foi estudar a espécie sob o aspecto botânico, químico e farmacológico. Assim, folhas e caules foram analisados macro e microscopicamente, contribuindo no auxílio da diagnose da espécie. Os órgãos em estudo foram submetidos a ensaios preliminares para a pesquisa dos principais grupos de princípios ativos provenientes do metabolismo secundário dos vegetais. Diferentes extratos foram obtidos por percolação e por decocção, sendo alguns deseus componentes isolados por CCD preparativa e identificadas por CG/EM. O óleoessencial do vegetal, coletado em diferentes épocas do ano e variados estágios de desenvolvimento, foi obtido em aparelho de Clevenger modificado, sendo que sua composição também foi analisada por CG/EM. O extrato clorofórmico e o extrato hidroetanólico liofilizado (EHL) foram avaliados quanto à atividade antimalárica e antileishmania. Com o EHL foi realizado também ensaio de atividade antiúlcera em ratos Wistar Hannover fêmeas e atividade antimicrobiana em bactérias e fungos. A espécie em estudo, nas condições deste trabalho, apresentou flavonóides, taninos, saponinas, óleo essencial e mucilagens. O extrato clorofórmico e hidroetanólico liofilizado, nas concentrações de 100 &#181;g/mL, provocaram 100% de morte dos protozoários de Plasmodium chabaudi AJ, porém ambos não apresentaram atividade em promastigotas de Leishmania (L.) chagasi nesta concentração. O EHL na concentração de 10 mg/mL demonstrou significativa atividade antifúngica contra o Aspergillus niger, não apresentando nenhuma atividade para Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli e Candida albicans. O mesmo extrato, na concentração de 400 mg/kg, administrada por via oral, mostrou-se com atividade antiúlcera aguda significativa, reduzindo a Área Total de Lesão (ATL) em 49,13% em relação ao controle. O óleo essencial, nas condições do experimento, apresentou diferenças qualitativas e quantitativas quando comparado a estudos já realizados, sendo constituído em sua maioria por sesquiterpenos dos grupos cadinano (&#945;-cadinol e &#948;-cadineno), cariofilano (&#946;-cariofileno) e, principalmente, germacrano (globulol). As análises permitiram concluir ainda que o isômero do espatulenol é o componente exclusivo e majoritário do óleo essencial de caule e o isômero do globulol, o componente presente em maior quantidade no óleo quando o vegetal encontra-se em fase de floração. / Acanthospermum australe (Loefl.) O. Kuntze, known popularly in Brazil as carrapichinho belongs to the family Asteraceae and it is used in the tradicional medicine as hepatic protector, diaforetic, blenorragic activity, antimalarial activity among others. The objective of the present work was to study this species under the aspect botanical, chemical and pharmacological. Thus, leaves and stems were analyzed macro and microscopic contributing in the aid of the diagnosis of species.The aerial parts in study were submitted to preliminary phytochemical screening for the research of the main groups of secondary metabolites of plants. Difterent extracts were obtained by percolation and for decoction being some of their components, isolated for TLC preparative and identified for GC/MS. The essential oil of the plants, collected at different seasons of the year and different development stadiums, it was obtained in a Clevenger apparatus, and it composition, was also analyzed by GC/MS. The chloroformic extract and liofilized hidroethanolic extract (LHE) were assayed for the antimalarial and antileishmania activities. Using LHE it was also assayed for the anti ulcer activity in mice Wistar Hannover females and antimicrobial activity in bacteria and fungi. The species in study, in conditions of this work, presented flavonoids, tannins, saponnins, essential oil and mucilages. The chloroformic extract and LHE in the concentrations of 100 &#181;g/mL caused 100% of death in the blood forms of Plasmodium chabaudi AJ, however none of them presented activity in blood forms of Leishmania (L.) chagasi in this concentration. LHE in the concentration of 10 mg/mL presented significant antifungal activity against the Aspergillus niger, and no activity against Staphy/ococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans. The same extract, in the concentration of 400 mg/kg, administered orally, presented significant antiulcerogenic activity, reducing the Total Area of Lesion (TAL) in 49,13% in relation to the control. The essential oil, in the conditions of the experiment, presented qualitative and quantitative difterences when compared to previous studies and constituted in its majority by sesquiterpenes of the cadinano groups (&#945;-cadinol and &#948;-cadinene), caryophyllano (&#946;-caryophyllene) and mainly, germacrano (globulol). The analyses still permit to conclude that the isomer of the spathulenol is the exclusive and mayor component of the essential oil in the stem. Isomer of the globulol is the representative present in mayor amount in the oil when the plant is in flower stadium