Discovery of a New Analgesic Peptide, Leptucin, from the Iranian Scorpion, <i>Hemiscorpius lepturus</i>

• Main Authors: Sedigheh Bagheri-Ziari, Delavar Shahbazzadeh, Soroush Sardari, Jean-Marc Sabatier, Kamran Pooshang Bagheri
• Format: Article
• Language: English
• Published: MDPI AG 2021-04-01
• Series: Molecules
• Subjects: leptucin; analgesic peptide; <i>Hemiscorpius lepturus</i>; scorpion
• Online Access: https://www.mdpi.com/1420-3049/26/9/2580

<i>Hemiscorpius lepturus </i>scorpion stings do not induce considerable pain based on epidemiological surveys conducted in the southwest part of Iran. Accordingly, this study was aimed to identify the analgesic molecule in <i>H. lepturus</i> venom by analyzing a cDNA library of the scorpion venom gland looking for sequences having homology with known animal venom analgesic peptides. The analgesic molecule is a cysteine rich peptide of 55 amino acids. the synthetic peptide was deprotected and refolded. RP-HPLC, Ellman’s, and DLS assays confirmed the refolding accuracy. Circular dichroism (CD) showed helix and beta sheet contents. This peptide, called leptucin, demonstrated 95% analgesic activity at the dose of 0.48 mg/kg in hot plate assay. Leptucin at the doses of 0.32, 0.48, and 0.64 mg/kg showed 100% activity in thermal tail flick test. No hemolysis or cytotoxicity was observed at 8 and 16 µg. Histopathology evaluations indicated no hepatotoxicity, nephrotoxicity, and cardiotoxicity. We thus report that leptucin is the analgesic agent of <i>H. lepturus</i> venom. Regarding the high in vivo efficacy of leptucin and the fact it shows no observable toxicity, it could be suggested as a drug lead in a preclinical study of acute pain as well as the study of its mechanism of action.