Neuroactive venom compounds obtained from Phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro
Abstract Background Spider venom is a rich cocktail of neuroactive compounds designed to prey capture and defense against predators that act on neuronal membrane proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic transmission through acetylcholine (ACh) hydrolysis - an exci...
Published in: | Journal of Venomous Animals and Toxins including Tropical Diseases |
---|---|
Main Authors: | , , , , , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
SciELO
2021
|
Subjects: | |
Online Access: | https://doi.org/10.1590/1678-9199-jvatitd-2021-0009 https://doaj.org/article/853ef5a0914347269ef3d4b30e24d705 |
id |
ftdoajarticles:oai:doaj.org/article:853ef5a0914347269ef3d4b30e24d705 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:853ef5a0914347269ef3d4b30e24d705 2023-05-15T15:15:00+02:00 Neuroactive venom compounds obtained from Phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro Simon Miguel M. Lopez Jeremey S. Aguilar Jerene Bashia B. Fernandez Angelic Gayle J. Lao Mitzi Rain R. Estrella Mark Kevin P. Devanadera Cydee Marie V. Ramones Aaron Joseph L. Villaraza Leonardo A. Guevarra Jr. Myla R. Santiago-Bautista Librado A. Santiago 2021-06-01T00:00:00Z https://doi.org/10.1590/1678-9199-jvatitd-2021-0009 https://doaj.org/article/853ef5a0914347269ef3d4b30e24d705 EN eng SciELO http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992021000100314&tlng=en https://doaj.org/toc/1678-9199 1678-9199 doi:10.1590/1678-9199-jvatitd-2021-0009 https://doaj.org/article/853ef5a0914347269ef3d4b30e24d705 Journal of Venomous Animals and Toxins including Tropical Diseases, Vol 27 (2021) Philippine spider venom Spider venoms Phlogiellus bundokalbo Neurological diseases Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 article 2021 ftdoajarticles https://doi.org/10.1590/1678-9199-jvatitd-2021-0009 2022-12-30T20:16:15Z Abstract Background Spider venom is a rich cocktail of neuroactive compounds designed to prey capture and defense against predators that act on neuronal membrane proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic transmission through acetylcholine (ACh) hydrolysis - an excitatory neurotransmitter - and beta-secretases (BACE) that primarily cleave amyloid precursor proteins (APP), which are, in turn, relevant in the structural integrity of neurons. The present study provides preliminary evidence on the therapeutic potential of Phlogiellus bundokalbo venom against neurodegenerative diseases. Methods Spider venom was extracted by electrostimulation and fractionated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption ionization-time flight mass spectrometry (MALDI-TOF-MS). Neuroactivity of the whole venom was observed by a neurobehavioral response from Terebrio molitor larvae in vivo and fractions were screened for their inhibitory activities against AChE and BACE in vitro. Results The whole venom from P. bundokalbo demonstrated neuroactivity by inducing excitatory movements from T. molitor for 15 min. Sixteen fractions collected produced diverse mass fragments from MALDI-TOF-MS ranging from 900-4500 Da. Eleven of sixteen fractions demonstrated AChE inhibitory activities with 14.34% (± 2.60e-4) to 62.05% (± 6.40e-5) compared with donepezil which has 86.34% (± 3.90e-5) inhibition (p > 0.05), while none of the fractions were observed to exhibit BACE inhibition. Furthermore, three potent fractions against AChE, F1, F3, and F16 displayed competitive and uncompetitive inhibitions compared to donepezil as the positive control. Conclusion The venom of P. bundokalbo contains compounds that demonstrate neuroactivity and anti-AChE activities in vitro, which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Journal of Venomous Animals and Toxins including Tropical Diseases 27 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Philippine spider venom Spider venoms Phlogiellus bundokalbo Neurological diseases Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 |
spellingShingle |
Philippine spider venom Spider venoms Phlogiellus bundokalbo Neurological diseases Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 Simon Miguel M. Lopez Jeremey S. Aguilar Jerene Bashia B. Fernandez Angelic Gayle J. Lao Mitzi Rain R. Estrella Mark Kevin P. Devanadera Cydee Marie V. Ramones Aaron Joseph L. Villaraza Leonardo A. Guevarra Jr. Myla R. Santiago-Bautista Librado A. Santiago Neuroactive venom compounds obtained from Phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro |
topic_facet |
Philippine spider venom Spider venoms Phlogiellus bundokalbo Neurological diseases Arctic medicine. Tropical medicine RC955-962 Toxicology. Poisons RA1190-1270 Zoology QL1-991 |
description |
Abstract Background Spider venom is a rich cocktail of neuroactive compounds designed to prey capture and defense against predators that act on neuronal membrane proteins, in particular, acetylcholinesterases (AChE) that regulate synaptic transmission through acetylcholine (ACh) hydrolysis - an excitatory neurotransmitter - and beta-secretases (BACE) that primarily cleave amyloid precursor proteins (APP), which are, in turn, relevant in the structural integrity of neurons. The present study provides preliminary evidence on the therapeutic potential of Phlogiellus bundokalbo venom against neurodegenerative diseases. Methods Spider venom was extracted by electrostimulation and fractionated by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption ionization-time flight mass spectrometry (MALDI-TOF-MS). Neuroactivity of the whole venom was observed by a neurobehavioral response from Terebrio molitor larvae in vivo and fractions were screened for their inhibitory activities against AChE and BACE in vitro. Results The whole venom from P. bundokalbo demonstrated neuroactivity by inducing excitatory movements from T. molitor for 15 min. Sixteen fractions collected produced diverse mass fragments from MALDI-TOF-MS ranging from 900-4500 Da. Eleven of sixteen fractions demonstrated AChE inhibitory activities with 14.34% (± 2.60e-4) to 62.05% (± 6.40e-5) compared with donepezil which has 86.34% (± 3.90e-5) inhibition (p > 0.05), while none of the fractions were observed to exhibit BACE inhibition. Furthermore, three potent fractions against AChE, F1, F3, and F16 displayed competitive and uncompetitive inhibitions compared to donepezil as the positive control. Conclusion The venom of P. bundokalbo contains compounds that demonstrate neuroactivity and anti-AChE activities in vitro, which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases. |
format |
Article in Journal/Newspaper |
author |
Simon Miguel M. Lopez Jeremey S. Aguilar Jerene Bashia B. Fernandez Angelic Gayle J. Lao Mitzi Rain R. Estrella Mark Kevin P. Devanadera Cydee Marie V. Ramones Aaron Joseph L. Villaraza Leonardo A. Guevarra Jr. Myla R. Santiago-Bautista Librado A. Santiago |
author_facet |
Simon Miguel M. Lopez Jeremey S. Aguilar Jerene Bashia B. Fernandez Angelic Gayle J. Lao Mitzi Rain R. Estrella Mark Kevin P. Devanadera Cydee Marie V. Ramones Aaron Joseph L. Villaraza Leonardo A. Guevarra Jr. Myla R. Santiago-Bautista Librado A. Santiago |
author_sort |
Simon Miguel M. Lopez |
title |
Neuroactive venom compounds obtained from Phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro |
title_short |
Neuroactive venom compounds obtained from Phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro |
title_full |
Neuroactive venom compounds obtained from Phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro |
title_fullStr |
Neuroactive venom compounds obtained from Phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro |
title_full_unstemmed |
Neuroactive venom compounds obtained from Phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro |
title_sort |
neuroactive venom compounds obtained from phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro |
publisher |
SciELO |
publishDate |
2021 |
url |
https://doi.org/10.1590/1678-9199-jvatitd-2021-0009 https://doaj.org/article/853ef5a0914347269ef3d4b30e24d705 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Journal of Venomous Animals and Toxins including Tropical Diseases, Vol 27 (2021) |
op_relation |
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1678-91992021000100314&tlng=en https://doaj.org/toc/1678-9199 1678-9199 doi:10.1590/1678-9199-jvatitd-2021-0009 https://doaj.org/article/853ef5a0914347269ef3d4b30e24d705 |
op_doi |
https://doi.org/10.1590/1678-9199-jvatitd-2021-0009 |
container_title |
Journal of Venomous Animals and Toxins including Tropical Diseases |
container_volume |
27 |
_version_ |
1766345392851517440 |