Meléndez-Martínez David, Ortega-Hernández Erika, Reza-Zaldívar Edwin Estefan, Carbajal-Saucedo Alejandro, Arnaud-Franco Gustavo, Gatica-Colima Ana, Plenge-Tellechea Luis Fernando, Antunes-Ricardo Marilena, Jacobo-Velázquez Daniel A, Mayolo-Deloisa Karla, Lozano Omar, Rito-Palomares Marco, Benavides Jorge
Tecnologico de Monterrey, Institute for Obesity Research, Ave. Eugenio Garza Sada Sur 2501, C.P. 64849, Monterrey, N.L., Mexico.
Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Centro de Biotecnología-FEMSA, Ave. Eugenio Garza Sada Sur 2501, C.P. 64849, Monterrey, N.L., Mexico.
Toxicon X. 2024 Sep 19;24:100209. doi: 10.1016/j.toxcx.2024.100209. eCollection 2024 Dec.
Animal venoms are natural products that have served as a source of novel molecules that have inspired novel drugs for several diseases, including for metabolic diseases such as type-2 diabetes and obesity. From venoms, toxins such as exendin-4 () and crotamine () have demonstrated their potential as treatments for obesity. Moreover, other toxins such as Phospholipases A and Disintegrins have shown their potential to modulate insulin secretion in vitro. This suggests an unexplored diversity of venom peptides with a potential anti-obesogenic in Mexican rattlesnake venoms. For that reason, this study explored the in vitro effect of Crotalus venom peptide-rich fractions on models for insulin resistance, adipocyte lipid accumulation, antioxidant activity, and inflammation process through nitric oxide production inhibition. Our results demonstrated that the peptide-rich fractions of , and were capable of reverting insulin resistance, enhancing glucose consumption to normal control; , and diminished the lipid accumulation on adipocytes by 20%; , and had the most significant cellular antioxidant activity, having nearly 80% of ROS inhibition. and inhibited nitric oxide production by about 85%. We demonstrated the potential of these peptides from venoms to develop novel drugs to treat type-2 diabetes and obesity. Moreover, we described for the first time that venom peptide fractions have antioxidant and inflammatory properties in vitro models.
动物毒液是天然产物,其所含的新型分子启发了多种疾病的新型药物研发,包括2型糖尿病和肥胖症等代谢疾病。从毒液中提取的毒素,如艾塞那肽-4()和巴曲酶()已显示出治疗肥胖症的潜力。此外,其他毒素,如磷脂酶A和去整合素,已在体外显示出调节胰岛素分泌的潜力。这表明墨西哥响尾蛇毒液中存在具有潜在抗肥胖作用的未被探索的多种毒液肽。因此,本研究通过抑制一氧化氮生成,探讨了富含响尾蛇毒液肽的组分对胰岛素抵抗模型、脂肪细胞脂质积累、抗氧化活性和炎症过程的体外影响。我们的结果表明,来自、和的富含肽的组分能够逆转胰岛素抵抗,将葡萄糖消耗量提高到正常对照水平;、和使脂肪细胞上的脂质积累减少了20%;、和具有最显著的细胞抗氧化活性,对活性氧的抑制率接近80%。和对一氧化氮生成的抑制率约为85%。我们证明了这些来自响尾蛇毒液的肽具有开发治疗2型糖尿病和肥胖症新药的潜力。此外,我们首次描述了响尾蛇毒液肽组分在体外模型中具有抗氧化和抗炎特性。