Assessment of antimicrobial, antiproliferative, and chemotactic properties of ranatuerin 2-PMe from cutaneous secretion of Lithobates palmipes (Spix, 1824) (Anura, Ranidae)

IF 2.4 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon Pub Date : 2025-09-05 DOI:10.1016/j.toxicon.2025.108565

Géssica Gomes Barbosa , Carlos José Correia de Santana , Tulíbia Laurindo Silva , Welthon de Souza Teotonio , Lucas Fontes , Raquel Takaya , Ricardo Bentes de Azevedo , Patrícia Maria Guedes Paiva , Osmindo Rodrigues Pires Júnior , Wagner Fontes , Mariana S. Castro , Thiago Henrique Napoleão

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Abstract

Lithobates palmipes is a frog species whose skin secretions contain peptides belonging to the ranatuerin, brevinin, and temporin families. In this study, the peptide ranatuerin-2PMe was isolated and evaluated for its antimicrobial, hemolytic, antiproliferative, and chemotactic activities. Ranatuerin-2PMe (2933.2 Da) was purified from L. palmipes skin secretions (collected via electrical stimulation) using reversed-phase high-performance liquid chromatography, and its primary structure was subsequently determined through Edman degradation. The peptide was then synthesized via solid-phase peptide synthesis. Ranatuerin-2PMe exhibited antibacterial activity against Staphylococcus aureus, Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae carbapenemase-producer (KPC), with minimal inhibitory concentrations ranging from 2 μM to 128 μM. It demonstrated low hemolytic activity (18.3 ± 1.2 %) at 128 μM. Furthermore, ranatuerin-2PMe showed antiproliferative effects against HeLa and HaCaT cell lines, with IC₅₀ values of 12.4 μM and 16.9 μM, respectively. Ranatuerin-2PMe induced neutrophil migration in a pattern consistent with chemotactic activity, while maintaining neutrophil viability. In conclusion, a novel peptide from the ranatuerin family was identified in L. palmipes skin secretions, demonstrating promising biomedical potential as an antimicrobial, anticancer, and immunomodulatory agent. However, its cytotoxicity toward HaCaT cells highlights the need for further studies to evaluate its selectivity and safety profile.

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棕榈贝（Lithobates palmipes, Spix, 1824）皮肤分泌物中ranatuerin 2-PMe的抗菌、抗增殖和趋化特性评估（无尾目，蛙科）。

棕榈岩蛙是一种蛙类，其皮肤分泌物中含有属于ranatuerin、brevinin和temporin家族的肽。本研究分离了ranatuerin-2PMe肽，并对其抗菌、溶血、抗增殖和趋化活性进行了评价。Ranatuerin-2PMe （2933.2 Da）采用反相高效液相色谱法从L. palmipes皮肤分泌物（通过电刺激收集）中纯化，随后通过Edman降解测定其一级结构。然后通过固相肽合成法合成该肽。Ranatuerin-2PMe对金黄色葡萄球菌、大肠杆菌、鲍曼不动杆菌、铜绿假单胞菌和肺炎克雷伯菌碳青霉烯酶产生菌（KPC）具有抑菌活性，最小抑菌浓度在2 μM ~ 128 μM之间。128 μM溶血活性低（18.3±1.2%）。此外，ranatuerin-2PMe对HeLa和HaCaT细胞株具有抗增殖作用，IC50值分别为12.4 μM和16.9 μM。Ranatuerin-2PMe以与趋化活性一致的模式诱导中性粒细胞迁移，同时保持中性粒细胞活力。总之，从棕榈乳杆菌的皮肤分泌物中鉴定出一种新的ranatuerin家族肽，显示出作为抗菌、抗癌和免疫调节剂的良好生物医学潜力。然而，其对HaCaT细胞的细胞毒性表明需要进一步研究以评估其选择性和安全性。

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来源期刊

Toxicon 医学-毒理学

CiteScore

4.80

自引率

10.70%

发文量

358

审稿时长

68 days

期刊介绍： Toxicon has an open access mirror Toxicon: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. An introductory offer Toxicon: X - full waiver of the Open Access fee. Toxicon''s "aims and scope" are to publish: -articles containing the results of original research on problems related to toxins derived from animals, plants and microorganisms -papers on novel findings related to the chemical, pharmacological, toxicological, and immunological properties of natural toxins -molecular biological studies of toxins and other genes from poisonous and venomous organisms that advance understanding of the role or function of toxins -clinical observations on poisoning and envenoming where a new therapeutic principle has been proposed or a decidedly superior clinical result has been obtained. -material on the use of toxins as tools in studying biological processes and material on subjects related to venom and antivenom problems. -articles on the translational application of toxins, for example as drugs and insecticides -epidemiological studies on envenoming or poisoning, so long as they highlight a previously unrecognised medical problem or provide insight into the prevention or medical treatment of envenoming or poisoning. Retrospective surveys of hospital records, especially those lacking species identification, will not be considered for publication. Properly designed prospective community-based surveys are strongly encouraged. -articles describing well-known activities of venoms, such as antibacterial, anticancer, and analgesic activities of arachnid venoms, without any attempt to define the mechanism of action or purify the active component, will not be considered for publication in Toxicon. -review articles on problems related to toxinology. To encourage the exchange of ideas, sections of the journal may be devoted to Short Communications, Letters to the Editor and activities of the affiliated societies.