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
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Online Access:https://ir.uitm.edu.my/id/eprint/54162/1/54162.pdf
https://ir.uitm.edu.my/id/eprint/54162/
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spelling my.uitm.ir.541622022-01-04T06:19:49Z https://ir.uitm.edu.my/id/eprint/54162/ Inhibitory effects of Malaysian fungal endophytic extracts on BACEl (β-secretase) and BV2 microglia-mediated inflammatory response / Azzeme Harun. 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 NonPeerReviewed text en https://ir.uitm.edu.my/id/eprint/54162/1/54162.pdf ID54162 Harun, Azzeme (2012) Inhibitory effects of Malaysian fungal endophytic extracts on BACEl (β-secretase) and BV2 microglia-mediated inflammatory response / Azzeme Harun. Masters thesis, thesis, Universiti Teknologi MARA.
institution Universiti Teknologi Mara
building Tun Abdul Razak Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Teknologi Mara
content_source UiTM Institutional Repository
url_provider http://ir.uitm.edu.my/
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
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.
publishDate 2012
url https://ir.uitm.edu.my/id/eprint/54162/1/54162.pdf
https://ir.uitm.edu.my/id/eprint/54162/
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