The underlying mechanism of scorpion venom peptide BmK AS in reducing epilepsy seizures: mediated through dual modulation of Nav1.6 and the inflammasome pathway

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  The underlying mechanism of scorpion venom peptide BmK AS in reducing epilepsy seizures: mediated through dual modulation of Nav1.6 and the inflammasome pathway Abstract Introduction:  Voltage-gated sodium channel (VGSC) dysregulation, particularly of the Nav1.6 subtype, is a core mechanism underlying epileptogenesis and its associated neuropsychiatric comorbidities. The scorpion venom peptide BmK AS has demonstrated anticonvulsant potential, but its efficacy in chronic epilepsy and the precise mechanisms of action remain undefined. Methods:  Here, we show that BmK AS exerts robust anti-epileptic and neuroprotective effects through converging mechanisms. In a kainic acid-induced mouse model, BmK AS treatment reduced mortality and seizure parameters. Electrophysiological studies assessed BmK AS modulation of VGSC subtypes. The functional relevance of Nav1.6 targeting was confirmed by the loss of BmK AS’s anti-seizure efficacy upon its pharmacological blockade in a PTZ-in...

Inhibitory effects of 6-O-palmitoyl-l-ascorbic acid (ASC16) on the enzymatic activity of Bothrops alternatus venom

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By Cláudio Timm - https://www.flickr.com/photos/cdtimm/4267955250/, CC BY-SA 2.0, https://commons.wikimedia.org/w/index.php?curid=13205355

Inhibitory effects of 6-O-palmitoyl-l-ascorbic acid (ASC16) on the enzymatic activity of Bothrops alternatus venom

Abstract

In the anti-venom production process, it is essential to use whole venom during immunization to generate specific antibodies capable of neutralizing all venom components. However, efforts are being made to improve the traditional immunization process by reducing the toxic effects of venom components on the immunized animals while ensuring an optimal immune response in accordance with good manufacturing practices. In this context, we aimed to evaluate the capacity of ASC16 to inhibit the enzymatic activity of the main components of B. alternatus venom. In vitro studies were conducted to evaluate the inhibitory effect of ASC16 on metalloproteinases (SVMP), serine proteinases (SVSP) and phospholipases A2 (PLA2) using specific substrates. In vivo assays measured edema-forming activity, and histological analysis with hematoxylin and eosin staining were performed. Additionally, hemorrhage inhibition was tested using a murine model. In silico studies were also carried out using bothropasin as a model. The results of enzyme inhibition showed that ASC16 significantly inhibited SVMP (49.31% ± 0.62), SVSP (63.11 ± 3.86%) and PLA2 activity (36.52% ± 0.09). ASC16 did not reduce edema but it significantly inhibited hemorrhage (66.32%). In silico analysis suggested that ASC16’s hydrophobic portion binds to critical residues involved in catalysis of the SVMP (Glu146 and His145), while the hydrophilic fraction also interacts with the protein (Pro109, Thr110, Gly112, and Tyr132). These findings position ASC16 as a promising candidate for use as an additive inhibitor in adjuvant formulations in antivenom immunization schemes for B. alternatus.

Maslovski, F., Pereañez, J.A., Hernández, D. et al. Inhibitory effects of 6-O-palmitoyl-l-ascorbic acid (ASC16) on the enzymatic activity of Bothrops alternatus venom. Arch Toxicol (2025). https://doi.org/10.1007/s00204-025-04188-9