Aquino Gabriel Angelo de, Sousa Caren Nádia Soares de, Santos Júnior Manuel Alves Dos, Cavalcante Letícia Régia Lima, Forte Ana Rizzia Cunha Cordeiro, Mota Mário Rogério Lima, Martínez Farah Essguí Orellana, Almeida Talysson Silva de, Leal Luzia Kalyne Almeida Moreira, Vasconcelos Silvânia Maria Mendes
Neuropsychopharmacology Laboratory, Drug Research and Development Center, Faculty of Medicine, Federal University of Ceará, Street Coronel Nunes de Melo, 1000, Fortaleza, CE, 60430-275, Brazil; Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Street Coronel Nunes de Melo, 1127 Fortaleza, CE, 60430-275, Brazil.
Department of Dental Clinic, Faculty of Pharmacy, Dentistry and Nursing, Federal University of Ceará, Street Alexandre Baraúna, 949, Fortaleza, CE, 60430-160, Brazil.
Eur J Pharmacol. 2025 Sep 5;1002:177769. doi: 10.1016/j.ejphar.2025.177769. Epub 2025 May 27.
This study evaluated the wound-healing effects of topical alpha-lipoic acid (ALA) in a mice pressure injury (PI) model and its association with behavioral and neurochemical alterations. Male Swiss mice (25-30 g) were assigned to control, SHAM, base cream, ALA cream, or alginate hydrogel groups. PI was induced through a 4-day ischemia/reperfusion protocol, followed by 10 days of treatment. Behavioral tests included the open field, splash, tail suspension, and social interaction tests. The prefrontal cortex (PFC), hippocampus (HC), and lesion tissue were collected to assess myeloperoxidase (MPO) activity. Lesion tissue was also analyzed for tumor necrosis factor alpha (TNF-α), healing progression, and histological parameters. SHAM animals exhibited reduced locomotor activity, increased immobility, impaired grooming, social withdrawal, weight loss, and elevated MPO and TNF-α levels. All treatments reversed some of these effects, but ALA cream consistently showed the most robust outcomes. It was the only treatment to maintain improved locomotion on day 10, fully restore grooming behavior, reverse weight loss, and promote angiogenesis. Additionally, ALA significantly reduced MPO and TNF-α levels in both central and peripheral tissues. Histological analysis confirmed reduced inflammation and enhanced vascular proliferation in ALA-treated wounds. These findings suggest that topical ALA promotes wound healing and may exert indirect antidepressant-like effects via modulation of inflammation. Given its accessibility and dual therapeutic action, ALA represents a promising candidate for improving wound healing and exerts an indirect antidepressant-like effect.
本研究评估了局部应用α-硫辛酸（ALA）对小鼠压力性损伤（PI）模型的伤口愈合作用及其与行为和神经化学改变的关联。将雄性瑞士小鼠（25 - 30克）分为对照组、假手术组、基础乳膏组、ALA乳膏组或藻酸盐水凝胶组。通过4天的缺血/再灌注方案诱导PI，随后进行10天的治疗。行为测试包括旷场试验、溅水试验、尾悬挂试验和社交互动试验。收集前额叶皮质（PFC）、海马体（HC）和损伤组织以评估髓过氧化物酶（MPO）活性。还对损伤组织进行肿瘤坏死因子α（TNF-α）、愈合进程和组织学参数分析。假手术动物表现出运动活动减少、不动时间增加、梳理行为受损、社交退缩、体重减轻以及MPO和TNF-α水平升高。所有治疗都逆转了其中一些影响，但ALA乳膏始终显示出最显著的效果。它是唯一在第10天能维持运动改善、完全恢复梳理行为、逆转体重减轻并促进血管生成的治疗方法。此外，ALA显著降低了中枢和外周组织中的MPO和TNF-α水平。组织学分析证实ALA治疗的伤口炎症减轻且血管增生增强。这些发现表明局部应用ALA可促进伤口愈合，并可能通过调节炎症发挥间接的抗抑郁样作用。鉴于其易获取性和双重治疗作用，ALA是改善伤口愈合和发挥间接抗抑郁样作用的有前景的候选药物。
