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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. Lopez1,4, Jeremey S. Aguilar1, Jerene Bashia B. Fernandez1, Angelic Gayle J. Lao1, Mitzi Rain R. Estrella1, Mark Kevin P. Devanadera1,2,3, Cydee Marie V. Ramones4, Aaron Joseph L. Villaraza4, Leonardo A. Guevarra Jr.1,2, Myla R. Santiago-Bautista1,2,3, Librado A. Santiago1,2,3 [ + show more ]

J Venom Anim Toxins incl Trop Dis, 2021, 27:e20210009
Received: 24 January 2021 | Accepted: 31 March 2021 | Published online: 28 June 2021
Collection: Arthropods: venoms and biology


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 vitroResults: 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.


Keywords: Philippine spider venom; Spider venoms; Phlogiellus bundokalbo; Neurological diseases.

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