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, Myla R Santiago-Bautista, Librado A Santiago
{"title":"神经活性毒液化合物作为神经退行性疾病的潜在线索:其体外乙酰胆碱酯酶和β -分泌酶抑制活性的见解。","authors":"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, Myla R Santiago-Bautista, Librado A Santiago","doi":"10.1590/1678-9199-JVATITD-2021-0009","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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 <i>Phlogiellus bundokalbo</i> venom against neurodegenerative diseases.</p><p><strong>Methods: </strong>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 <i>Terebrio molitor</i> larvae <i>in vivo</i> and fractions were screened for their inhibitory activities against AChE and BACE <i>in vitro</i>.</p><p><strong>Results: </strong>The whole venom from <i>P. bundokalbo</i> demonstrated neuroactivity by inducing excitatory movements from <i>T. molitor</i> 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.</p><p><strong>Conclusion: </strong>The venom of <i>P. bundokalbo</i> contains compounds that demonstrate neuroactivity and anti-AChE activities <i>in vitro</i>, which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases.</p>","PeriodicalId":520810,"journal":{"name":"The journal of venomous animals and toxins including tropical diseases","volume":" ","pages":"e20210009"},"PeriodicalIF":0.0000,"publicationDate":"2021-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237997/pdf/","citationCount":"0","resultStr":"{\"title\":\"Neuroactive venom compounds obtained from <i>Phlogiellus bundokalbo</i> as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities <i>in vitro</i>.\",\"authors\":\"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, Myla R Santiago-Bautista, Librado A Santiago\",\"doi\":\"10.1590/1678-9199-JVATITD-2021-0009\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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 <i>Phlogiellus bundokalbo</i> venom against neurodegenerative diseases.</p><p><strong>Methods: </strong>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 <i>Terebrio molitor</i> larvae <i>in vivo</i> and fractions were screened for their inhibitory activities against AChE and BACE <i>in vitro</i>.</p><p><strong>Results: </strong>The whole venom from <i>P. bundokalbo</i> demonstrated neuroactivity by inducing excitatory movements from <i>T. molitor</i> 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.</p><p><strong>Conclusion: </strong>The venom of <i>P. bundokalbo</i> contains compounds that demonstrate neuroactivity and anti-AChE activities <i>in vitro</i>, which could comprise possible therapeutic leads for the development of cholinergic compounds against neurological diseases.</p>\",\"PeriodicalId\":520810,\"journal\":{\"name\":\"The journal of venomous animals and toxins including tropical diseases\",\"volume\":\" \",\"pages\":\"e20210009\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2021-06-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237997/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"The journal of venomous animals and toxins including tropical diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1590/1678-9199-JVATITD-2021-0009\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2021/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"The journal of venomous animals and toxins including tropical diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1590/1678-9199-JVATITD-2021-0009","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2021/1/1 0:00:00","PubModel":"eCollection","JCR":"","JCRName":"","Score":null,"Total":0}
Neuroactive venom compounds obtained from Phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro.
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.
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