Inhibitory effects of Malaysian fungal endophytic extracts on BACEl (β-secretase) and BV2 microglia-mediated inflammatory response / Azzeme Harun.

BACE1 is the major (β-secretase in neurons and its appearance and activity were found to be elevated in the brain of Alzheimer's disease patients. In the present study, fungal endophytic extracts of BACE1 inhibitory activity and cytotoxicity against PC-12 (a rat pheochromocytoma with neuronal p...

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Main Author:	Harun, Azzeme
Format:	Thesis
Language:	English
Published:	2012
Subjects:	Immunochemistry Fungal antigens
Online Access:	https://ir.uitm.edu.my/id/eprint/54162/1/54162.pdf
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id	my-uitm-ir.54162
record_format	uketd_dc
spelling	my-uitm-ir.541622022-01-04T06:19:49Z Inhibitory effects of Malaysian fungal endophytic extracts on BACEl (β-secretase) and BV2 microglia-mediated inflammatory response / Azzeme Harun. 2012 Harun, Azzeme Immunochemistry Fungal antigens BACE1 is the major (β-secretase in neurons and its appearance and activity were found to be elevated in the brain of Alzheimer's disease patients. In the present study, fungal endophytic extracts of BACE1 inhibitory activity and cytotoxicity against PC-12 (a rat pheochromocytoma with neuronal properties) and WRL68 (a non-tumorigenic human hepatic) were investigated. This study also investigated the anti-neuroinflammatory activities of five endophytic extracts (HAB16R12, HAB16R13, HAB16R14, HAB16R18 and HAB8R24) for inhibition of nitric oxide (NO), CD40 phenotype and pro- and anti-inflammatory cytokine production in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. Endophytes were isolated from plants collected from Kuala Pilah, Negeri Sembilan and the National Park, Pahang. For investigation of biological activity, the pure endophytic cultures were cultivated for 14 days on PDA plates at 28°C and underwent semipolar extraction with ethyl acetate. From 212 endophytic extracts (1000 µg/ml), 29 exhibited more than 90% inhibition of BACE1 in the preliminary screening. Four extracts from isolates HAB16R13, HAB16R14, HAB16R18 and HAB8R24 identified as Cytospora rhizophorae were the most active with IC5O(BACEI) values of less than 3.0 µg/ml. The most active extract HAB16R13 was shown to non-competitively inhibit BACE1 with Rvalue of 10.0 (µg/ml. HAB16R13 was considered non-potent against PC- 12 (IC5o(CT) of 60.0) and WRL68 (IC50(CT) of 40.0 µg/ml). Microglia treated with the five endophytic extracts (0.1 mg/ml) exhibited reduction of NO production without causing any effect on cell viability. CD40 expression in LPS-stimulated microglia was not significantly different in the presence or absence of endophytic extracts. In unstimulated BV2 cells, only extract HAB16R13 significantly (p<0.05) reduced CD40 expression after 48 h. All five extracts significantly (p<0.05) inhibited expression of the proinflammatory cytokines, IL-6 and TNF-α in LPS-stimulated microglia. This first report on endophytic fungal extract with BACE1 inhibitory activity and anti-neuroinflammatory properties demonstrates that more extensive study is required to uncover the potential of endophytes and could be utilized in the treatment of neurodegenerative diseases. 2012 Thesis https://ir.uitm.edu.my/id/eprint/54162/ https://ir.uitm.edu.my/id/eprint/54162/1/54162.pdf text en public masters Universiti Teknologi MARA Faculty of Pharmacy
institution	Universiti Teknologi MARA
collection	UiTM Institutional Repository
language	English
topic	Immunochemistry Fungal antigens
spellingShingle	Immunochemistry Fungal antigens Harun, Azzeme Inhibitory effects of Malaysian fungal endophytic extracts on BACEl (β-secretase) and BV2 microglia-mediated inflammatory response / Azzeme Harun.
description	BACE1 is the major (β-secretase in neurons and its appearance and activity were found to be elevated in the brain of Alzheimer's disease patients. In the present study, fungal endophytic extracts of BACE1 inhibitory activity and cytotoxicity against PC-12 (a rat pheochromocytoma with neuronal properties) and WRL68 (a non-tumorigenic human hepatic) were investigated. This study also investigated the anti-neuroinflammatory activities of five endophytic extracts (HAB16R12, HAB16R13, HAB16R14, HAB16R18 and HAB8R24) for inhibition of nitric oxide (NO), CD40 phenotype and pro- and anti-inflammatory cytokine production in lipopolysaccharide (LPS)-stimulated BV2 microglia cells. Endophytes were isolated from plants collected from Kuala Pilah, Negeri Sembilan and the National Park, Pahang. For investigation of biological activity, the pure endophytic cultures were cultivated for 14 days on PDA plates at 28°C and underwent semipolar extraction with ethyl acetate. From 212 endophytic extracts (1000 µg/ml), 29 exhibited more than 90% inhibition of BACE1 in the preliminary screening. Four extracts from isolates HAB16R13, HAB16R14, HAB16R18 and HAB8R24 identified as Cytospora rhizophorae were the most active with IC5O(BACEI) values of less than 3.0 µg/ml. The most active extract HAB16R13 was shown to non-competitively inhibit BACE1 with Rvalue of 10.0 (µg/ml. HAB16R13 was considered non-potent against PC- 12 (IC5o(CT) of 60.0) and WRL68 (IC50(CT) of 40.0 µg/ml). Microglia treated with the five endophytic extracts (0.1 mg/ml) exhibited reduction of NO production without causing any effect on cell viability. CD40 expression in LPS-stimulated microglia was not significantly different in the presence or absence of endophytic extracts. In unstimulated BV2 cells, only extract HAB16R13 significantly (p<0.05) reduced CD40 expression after 48 h. All five extracts significantly (p<0.05) inhibited expression of the proinflammatory cytokines, IL-6 and TNF-α in LPS-stimulated microglia. This first report on endophytic fungal extract with BACE1 inhibitory activity and anti-neuroinflammatory properties demonstrates that more extensive study is required to uncover the potential of endophytes and could be utilized in the treatment of neurodegenerative diseases.
format	Thesis
qualification_level	Master's degree
author	Harun, Azzeme
author_facet	Harun, Azzeme
author_sort	Harun, Azzeme
title	Inhibitory effects of Malaysian fungal endophytic extracts on BACEl (β-secretase) and BV2 microglia-mediated inflammatory response / Azzeme Harun.
title_short	Inhibitory effects of Malaysian fungal endophytic extracts on BACEl (β-secretase) and BV2 microglia-mediated inflammatory response / Azzeme Harun.
title_full	Inhibitory effects of Malaysian fungal endophytic extracts on BACEl (β-secretase) and BV2 microglia-mediated inflammatory response / Azzeme Harun.
title_fullStr	Inhibitory effects of Malaysian fungal endophytic extracts on BACEl (β-secretase) and BV2 microglia-mediated inflammatory response / Azzeme Harun.
title_full_unstemmed	Inhibitory effects of Malaysian fungal endophytic extracts on BACEl (β-secretase) and BV2 microglia-mediated inflammatory response / Azzeme Harun.
title_sort	inhibitory effects of malaysian fungal endophytic extracts on bacel (β-secretase) and bv2 microglia-mediated inflammatory response / azzeme harun.
granting_institution	Universiti Teknologi MARA
granting_department	Faculty of Pharmacy
publishDate	2012
url	https://ir.uitm.edu.my/id/eprint/54162/1/54162.pdf
_version_	1783734887225753600

Inhibitory effects of Malaysian fungal endophytic extracts on BACEl (β-secretase) and BV2 microglia-mediated inflammatory response / Azzeme Harun.

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