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An investigation into the antidepressant activity of hypericum perforatumStephens, Linda Lee January 2005 (has links)
Hypericum perforatum is a herbal medicine that has been used for centuries for the treatment of depression. Many studies have been conducted in the Northern hemisphere on the efficacy of the HP extracts produced there. These studies include clinical trials and pharmacological investigations using a standardised HP extract or a fraction of the HP extract containing certain compounds, such as hypericin, pseudohypericin, hyperforin and several of the flavonoids thought to be responsible for the antidepressant activity. The mechanism of action of HP and its constituents is still not completely clear and it is speculated that the antidepressant activity is the result of several of the compounds acting synergistically. HP is indigenous to and also cultivated in the Western Cape of South Africa. Extracts from these plants are sold in the local health shops and there are no previous studies evaluating the efficacy of these products. The aim of this thesis is to investigate the antidepressant activity of one of these products and two of its constituents, quercetin and caffeic acid, to gain further insight into their mode of antidepressant action and to compare these results with similar studies which used a standardised extract produced in the northern hemisphere. The first study investigated the effect of HP, quercetin and caffeic acid on pineal metabolism. Changes in the synthesis of melatonin produced by the pineal gland have been implicated in depression. The results showed an increase in the level of melatonin produced in the animals treated with quercetin, which suggests that this compound may mediate antidepressant activity through such a mechanism. There are no previous reports on the in vivo effects of HP or any of its constituents on pineal metabolism. The second study investigated the effect of HP, quercetin and caffeic acid on the activity of the liver enzyme, tryptophan-2,3-dioxygenase (TDO). Inhibition of this enzyme has been shown to increase plasma levels of tryptophan, a precursor of serotonin and thereby result in increased serotonin levels in the brain. Low levels of serotonin in the brain have been implicated in depression. This study revealed significant inhibition of TDO by caffeic acid and this suggests that this constituent of HP could be contributing to its antidepressant activity through such a mechanism. There are no previous reports investigating the in vivo effect of HP or any of its constituents on TDO activity. Modulation of the levels of indoleamines, serotonin (5-HT) and dopamine (DA) as well as the metabolites, 3,4 dihydroxyphenyl acetic acid (DOPAC), 5-hydroxyindole acetic acid (5-HIAA) and homovallinic acid (HVA) in the brain have been implicated in the neuropharmacology of depression. Different studies using enzyme-linked immunosorbant assay (ELISA), high performance liquid chromatography with electrochemical detection (HPLC-ECD) and liquid chromatography-mass spectrometry (LC-MS) were used to determine changes in the levels of these indoleamines brought about after treatment with HP caffeic acid and quercetin. The results of the ELISA study showed significant increases in 5-HT levels in the brains of the animals treated with caffeic acid and quercetin. The results of the HPLC-ECD studies also revealed significant increases in 5-HT levels and a decrease in the turnover of 5-HT in the animals treated with quercetin. A significant increase in DA levels in the animals treated with quercetin was shown in both the HPLC-ECD and LC-MS studies. There was also an increase in DA turnover in the animals treated with HP shown in the HPLC-ECD and LC-MS studies. These results suggest that HP and its constituents, quercetin and caffeic acid mediate their antidepressant effects through serotonergic and dopaminergic neurotransmission. Adaptive changes in the density of b-adrenergic (b-AR), 5-HT2 and N-methyl-D-aspartate (NMDA) receptors have been implicated in depression. Several studies, investigating the effect of treatment with HP and quercetin on these different receptor densities, were undertaken using radioactive binding assays. Treatment with HP resulted in significant down regulation of b-AR and NMDA receptor densities and up-regulation of 5HT2 receptors. The effects on the b-AR and 5-HT2 receptors are similar to the results reported using HP in the Northern hemisphere, but the effect on the NMDA receptors is novel providing insight into the mode of action of HP. Apoptosis of neuronal cells has been implicated in neuro-degenerative and depressive disorders. Detection of apoptosis, using fluorescent microscopy observed through the labelling of DNA strand breaks, showed a decrease in the amount of apoptosis in the animals treated with HP and quercetin. This adds further support for the use of HP as an antidepressant and these results are similar to results reported from the Northern hemisphere. The results of all these studies suggest that the quality of the locally produced tincture is similar in efficacy to that of the standardised product of the Northern hemisphere.
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Pharmaceutical analysis and aspects of the quality control of St. John's Wort productsWild, Tracy Joy January 2003 (has links)
Most complementary medicines contain a multitude of chemical components, some of which are claimed to contribute to the biological activity of such products. Use of complementary medicines for preventative and therapeutic purposes is increasing rapidly worldwide. Unfortunately, although control of these products is essential to ensure quality, safety, and efficacy, the quality control of most herbal preparations is currently poor to non-existent, with little or no safety and efficacy data required to support the marketing and use of these products. The objective of this study was therefore to develop suitable analytical methods to qualitatively and quantitatively analyse the relevant components (rutin, isoquercitrin, hyperoside, quercitrin, quercetin, kaempferol, hypericin, pseudohypericin and hyperforin) in St John's Wort dosage forms for quality control purposes. A gradient HPLC method using a Luna 5·mC₁₈(2) 150 x 2.00mm internal diameter (i.d.) column and UV detection, was developed for the separation of six of the relevant flavonoid compounds in St John's Wort, namely rutin, isoquercitrin, hyperoside, quercitrin, quercetin and kaempferol. The development process involved a systematic investigation of gradient conditions, flow rate, and temperature. This method was subsequently applied to assay selected commercially available St John's Wort products. This system provided the necessary accuracy, precision and reproducibility and was associated with several advantages when compared to using standard bore (4.60 mm i.d.) HPLC columns. The method developed is currently the only known method that separates all six relevant flavonoids in a reasonable run time (less than 20 minutes). It is also one of the few methods that has sufficient separation between rutin, isoquercitrin and hyperoside. A qualitative method for the fingerprinting of flavonoid components was also developed, using capillary electrophoresis (CE). CE is a rapidly growing powerful analytical technique for the separation of charged compounds. Micellar electrokinetic chromatography (MEKC) is a very powerful electrophoretic technique that is capable of selectively resolving both neutral and ionic solutes in a single run. A MEKC method suitable for the separation and determination of various flavonoid constituents used as marker compounds in Hypericum perforatum was developed. Investigations into the effect of pH, ionic strength, applied voltage and capillary dimensions on separation were performed. The optimised method was then applied to qualitatively analyse various St John's Wort products on the market. This method was found to be advantageous in that it was simple, cost-effective, required minimal sample preparation and utilised very small quantities of sample. Due to the vast differences in chemical properties between the various marker and active components in St John's Wort, it was necessary to develop separate analytical methods for the flavonoids and for the other three relevant compounds (hypericin, pseudohypericin and hyperforin). An isocratic HPLC method using a Luna 5·mC₁₈(2) 150 x 2.00mm (i.d.) column and UV detection was developed for the separation of hypericin, pseudohypericin and hyperforin. The development process involved a systematic investigation of buffer molarity, mobile phase composition, pH, flow rate, and temperature. This method was subsequently applied to assay selected commercially available St John's Wort products on the South African market. This system also provided the necessary accuracy, precision and reproducibility, as well as the advantages associated with the use of a narrow bore column as opposed to the use of the more commonly used wider bore columns. This method was validated and used to quantitate these three compounds in various commercial St John's Wort products. By applying this method to liquid chromatography – tandem mass spectrometry (LC-MS-MS), qualitative analyses of the same products was performed to obtain confirmation of the quantitative HPLC results. Mass spectrometry is a powerful detection tool that is more selective and specific than many detection systems used with HPLC. Natural medicines usually constitute a multitude of constituents with much potential interference. In this regard LC-MS-MS is a powerful tool, with its ability to unequivocally identify target analytes regardless of the presence of interferences or complex matrices. ESI-MS-MS was used for the qualitative analysis of the content of the naphthodianthrones and hyperforin in the respective tablet products assayed with HPLC. LC-MS-MS analyses were performed in order to identify the constituents and to verify the specificity of the HPLC method. High inter-product and inter-batch variability was observed for all nine compounds assayed. These quantitative results were confirmed with the respective qualitative analyses. This study confirms the need for strict quality control of herbal medicinal products commercially available to consumers.
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An examination of neuroprotective effects of 17B-estradiol and extracts from Panax Quinquefolius L., Ginkgo Biloba and HypericumPerforatum against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)induced nigral-striatal neuronal degenerationChan, Wing-yan, Veronica, 陳詠恩 January 2001 (has links)
published_or_final_version / Anatomy / Master / Master of Philosophy
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