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https://ptsldigital.ukm.my/jspui/handle/123456789/485664| Title: | Inhibitory effects of phyllanthus amarus, phyllanthus urinaria, gynura segetum and gendarussa vulgaris on innate immune response |
| Authors: | Yuandani (P63477) |
| Supervisor: | Ibrahim Jantan, Prof. Dr. |
| Keywords: | Therapeutic activities Phyllanthus amarus P. urinaria Gynura segetum Gendarussa vulgaris Phagocytes Chromatographic techniques Dissertations, Academic -- Malaysia Universiti Kebangsaan Malaysia -- Dissertations |
| Issue Date: | 26-Oct-2015 |
| Description: | Many therapeutic activities of plant extracts and their isolates have been proposed to be due to their effects on the immune system. This study was carried out to determine the immunomodulatory activities of Phyllanthus amarus, P. urinaria, Gynura segetum and Gendarussa vulgaris as well as their isolates on phagocytes and lymphocytes. The components of the extracts were isolated by various chromatographic techniques and identified spectroscopically. The extracts were also qualitatively and quantitatively analyzed by reversed phase HPLC. The plant extracts and their isolates were evaluated for their effects on chemotaxis, β2 integrin (CD18) expression, phagocytosis, reactive oxygen species (ROS) and nitric oxide (NO) productions of phagocytes as well as lymphocyte proliferation and secretion of cytokines. Chemotactic activity was analyzed using the Boyden chamber technique, inhibition of CD18 expression and phagocytosis activity were determined with the aid of flow cytometry whilst ROS production was determined by a luminol-based chemiluminescence assay. Cytokines release was measured by ELISA, NO production was determined by griess assay whilst lymphocytes proliferation was investigated by liquid scintillation counter. HPLC analysis of the methanol extracts of P. amarus and P. urinaria led to the identification and quantification of phyllanthin and hypophyllanthin. Gallic acid was identified in the methanol extracts of Ge. vulgaris and Gy. segetum while the latter also contained rutin. Three new compounds, ethyl-8- hydroxy-8-methyl-tridecanoate, 7β,19α dihydroxy-urs-12-ene and 1,7,8-trihydroxy-2- naphtaldehyde, were isolated from P. amarus. A new chalcone, 4,4',5-trihydroxy chalcone and a new naphtalene derivative, 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5- triol were isolated from Gy. segetum. All the extracts and compounds tested exhibited strong inhibitory effects on chemotaxis, ROS and NO production as well as lymphocytes proliferation. Only some samples significantly inhibited β2 integrin (CD18) expression, phagocytosis, and secretion of proinflammatory cytokines. Amongst the samples tested, 8,8'-(ethene-1,2-diyl)-dinaphtalene-1,4,5-triol isolated from Gy. segetum depicted the strongest inhibitory activities on migration of PMNs towards chemoattractant with an IC50 value of 0.84 μg/mL which was lower than that of ibuprofen (1.42 μg/mL). This compound also showed the strongest inhibitory activity on the oxidative burst of zymosan and PMA stimulated leukocytes with IC50 values lower than aspirin. Of all the samples, phyllanthin at 50 μg/mL exhibited the highest engulfment inhibitory activity with percentage of phagocytizing cells of 14.2 and 27.1% for PMNs and monocytes, respectively. Except for phyllanthin and hypophyllanthin, all the other compounds showed weak inhibiton on CD18 expression. Amongst all the compounds tested, 4,4',5-trihydroxy chalcone, revealed the strongest inhibitory activity on lymphocytes proliferation with an IC50 value of 0.39 μg/mL which was ten times higher than prednisolone. 3β-Hydroxy-olea-6-en isolated from Ge. vulgaris exhibited the strongest inhibitory activity on TNF-α whereas 4,4',5-trihydroxy chalcone which was isolated from Gy. segetum showed the strongest inhibitory activity on IL-1β release. In conclusion, the compounds selectively suppress the innate immune responses at different steps. Thus these compounds could be developed into lead structures for development of immunotherapeutic agents.,Ph.D. |
| Pages: | 290 |
| Call Number: | QV20.5.Y94i 2015 9 tesis |
| Publisher: | UKM, Kuala Lumpur |
| Appears in Collections: | Faculty of Pharmacy / Fakulti Farmasi |
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|---|---|---|---|---|
| ukmvital_84844+Source01+Source010.PDF Restricted Access | 1.25 MB | Adobe PDF |  View/Open |
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