Neuroactive venom compounds obtained from Phlogiellus bundokalbo as potential leads for neurodegenerative diseases: insights on their acetylcholinesterase and beta-secretase inhibitory activities in vitro .

Autor:	Lopez SMM; Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines, 1008.; Institute of Chemistry, College of Science, University of the Philippines Diliman, Quezon City, Philippines, 1101., Aguilar JS; Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines, 1008., Fernandez JBB; Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines, 1008., Lao AGJ; Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines, 1008.; Research Center for Natural and Applied Sciences, University of Santo Tomas, Manila, Philippines, 1015.; The Graduate School, University of Santo Tomas, Manila, Philippines, 1015.; Institute of Chemistry, College of Science, University of the Philippines Diliman, Quezon City, Philippines, 1101., Estrella MRR; Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines, 1008., Devanadera MKP; Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines, 1008.; Research Center for Natural and Applied Sciences, University of Santo Tomas, Manila, Philippines, 1015.; The Graduate School, University of Santo Tomas, Manila, Philippines, 1015., Ramones CMV; Institute of Chemistry, College of Science, University of the Philippines Diliman, Quezon City, Philippines, 1101., Villaraza AJL; Institute of Chemistry, College of Science, University of the Philippines Diliman, Quezon City, Philippines, 1101., Guevarra LA Jr; Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines, 1008.; Research Center for Natural and Applied Sciences, University of Santo Tomas, Manila, Philippines, 1015., Santiago-Bautista MR; Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines, 1008.; Research Center for Natural and Applied Sciences, University of Santo Tomas, Manila, Philippines, 1015.; The Graduate School, University of Santo Tomas, Manila, Philippines, 1015., Santiago LA; Department of Biochemistry, Faculty of Pharmacy, University of Santo Tomas, Manila, Philippines, 1008.; Research Center for Natural and Applied Sciences, University of Santo Tomas, Manila, Philippines, 1015.; The Graduate School, University of Santo Tomas, Manila, Philippines, 1015.
Jazyk:	angličtina
Zdroj:	The journal of venomous animals and toxins including tropical diseases [J Venom Anim Toxins Incl Trop Dis] 2021 Jun 28; Vol. 27, pp. e20210009. Date of Electronic Publication: 2021 Jun 28 (Print Publication: 2021).
DOI:	10.1590/1678-9199-JVATITD-2021-0009
Abstrakt:	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. Competing Interests: Competing interests: The authors declare that they have no competing interests.
Databáze:	MEDLINE
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