BotAF, a new Buthus occitanus tunetanus scorpion toxin, produces potent analgesia in rodents

Abstract

This work reports the purification of new potent scorpion neuropeptide, named BotAF, by an activity-guided screening approach. BotAF is a 64-residue long-chain peptide that shares very high similarity with the original β-like scorpion toxin group, in which several peptides have been characterized to be anti-nociceptive in rodents. BotAF administration to rodents does not produce any toxicity or motor impairment, including at high doses. In all models investigated, BotAF turned out to be an efficient peptide in abolishing acute and inflammatory (both somatic and visceral) pain in rodents. It performs with high potency compared to standard analgesics tested in the same conditions. The anti-nociceptive activity of BotAF depends on the route of injection: it is inactive when tested by i.c.v. or i.v. routes but gains in potency when pre-injected locally (in the same compartment than the irritant itself) or by i.t. root 40 to 60 min before pain induction, respectively. BotAF is not an AINS-like compound as it fails to reduce inflammatory edema. Also, it does not activate the opioidergic system as its activity is not affected by naloxone. BotAF does also not bind onto RyR and has low activity towards DRG ion channels (particularly TTX sensitive Na channels) and does not bind onto rat brain synaptosome receptors. In somatic and visceral pain models, BotAF dose-dependently inhibited lumbar spinal cord c-fos/c-jun mRNA up regulation. Altogether, our data favor a spinal or peripheral anti-nociceptive mode of action of BotAF.

Anti-inflammatory activities of arthropod peptides: a systematic review

“…Furthermore, Ts14 reduced TNF-α levels and neutrophil infiltration, although stimulated macrophage infiltration into implants, as determined by myeloperoxidase (MPO) and N-acetyl-β-d-glucosaminidase (NAG) enzyme activities, respectively [ 114 ]. BotAF is a peptide derived from Buthus occitanus tunetanus (common yellow scorpion), another yellow scorpion species that comprises a long chain of 64 amino acid residues, with potent analgesic activity in rodents [ 115 ]. From the Chinese scorpion Mesobuthus martensii (Chinese scorpion), 35 scorpion oligopeptides (CMOs) were studied.…”

A Systematic Review of Traditionally Used Herbs and Animal-Derived Products as Potential Analgesics

“…In a study by Maatooug et al . [ 132 ], a new scorpion toxin, Buthus occitanus tunetanus (BotAF), was analyzed for its potent analgesic effect in rodents. The antinociceptive writhing test revealed a positive analgesic effect up to 50%, even after 90 min after the BotAF (5 mg/kg; intraperitoneal) injection.…”

“…Maatoug et al . [ 132 ] stated that several analgesic compounds were derived from animals; however, to date, ziconotide is the only toxin-derived medicine used in clinics to treat pain. The major challenges posed when translating preclinical trials to therapeutics are: (i) reaching the right potency and selectivity and (ii) providing the correct target accessibility and coverage.…”

Unveiling the Pain Relief Potential: Harnessing Analgesic Peptides from Animal Venoms

“…Different toxins from the scorpion Buthus martensii are promising for the treatment of pain in a xenograft tumor mouse model [ 77 , 78 ]. These toxins can be important candidates also to use in acute thermal pain model induced by a hot plate, in acute inflammation model induced by formalin [ 79 , 80 , 81 , 82 ], in a mouse-twisting pain model, mechanical allodynia, in a nociception model induced by a shutter-controlled lamp, and in an inflammation model induced by formalin and acetic acid writhing [ 81 ]. Furthermore, TsNTxP isolated from Tityus serrulatus venom proved to be a good candidate in acute nociception induced by a water bath and a neuropathic pain model induced by the constriction of a sciatic nerve (CCI model) [ 83 ], while Leptucin from Hemiscorpius lepturus venom showed analgesic potential against an acute thermal pain model induced by a hot plate and a nociception model using the tail-flick test [ 84 ].…”