Department of Medical Biotechnology and Integrative Physiology, Institute of Biotechnology, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Thandalam, Chennai, Tamil Nadu, India.
Department of Cariology, Saveetha Dental College and Hospitals, SIMATS, Chennai, Tamil Nadu, India.
J Biochem Mol Toxicol. 2024 Nov;38(11):e70027. doi: 10.1002/jbt.70027.
HO is a significant reactive oxygen species (ROS) that hinders redox-mediated processes and contributes to oxidative stress and neurodegenerative disorders. Oxidative stress causes impairment of cell macromolecules, which results in cell dysfunction and neurodegeneration. Alzheimer's disease and other neurodegenerative diseases are serious conditions linked to oxidative stress. Antioxidant treatment approaches are a novel and successful strategy for decreasing neurodegeneration and reducing oxidative stress. This study explored the antioxidant and neuroprotective characteristics of KK14 peptide synthesized from LEAP 2B (liver-expressed antimicrobial peptide-2B) derived from Cyprinus carpio L. Molecular docking studies were used to assess the antioxidant properties of KK14. The peptide at concentrations 5-45 μM was examined by using in vitro and in vivo assessment. Analysis was done on the developmental and neuroprotective potential of KK14 peptide treatment in HO-exposed zebrafish larvae which showed Nonlethal deformities. KK14 improves antioxidant enzyme activity like catalase and superoxide dismutase. Furthermore, it reduces neuronal damage by lowering lipid peroxidation and nitric oxide generation while increasing acetylcholinesterase activity. It improved the changes in swimming behavior and the cognitive damage produced by exposure to HO. To further substantiate the neuroprotective potential of KK14, intracellular ROS levels in zebrafish larvae were assessed. This led to a reduction in ROS levels and diminished lipid peroxidation. The KK14 has upregulated the antioxidant genes against oxidative stress. Overall, this study proved the strong antioxidant activity of KK14, suggesting its potential as a strong therapeutic option for neurological disorders caused by oxidative stress.
HO 是一种重要的活性氧（ROS），它会阻碍氧化还原介导的过程，导致氧化应激和神经退行性疾病。氧化应激会导致细胞大分子受损，从而导致细胞功能障碍和神经退行性变。阿尔茨海默病和其他神经退行性疾病是与氧化应激相关的严重疾病。抗氧化治疗方法是减少神经退行性变和减轻氧化应激的一种新颖而成功的策略。本研究探索了从鲤鱼（Cyprinus carpio L.）的 LEAP 2B（肝表达抗菌肽-2B）衍生而来的 KK14 肽的抗氧化和神经保护特性。使用分子对接研究评估了 KK14 的抗氧化特性。通过体外和体内评估研究了浓度为 5-45 μM 的肽。对 KK14 肽处理暴露于 HO 的斑马鱼幼虫的发育和神经保护潜力进行了分析，结果显示其具有非致死性畸形。KK14 可提高过氧化氢酶和超氧化物歧化酶等抗氧化酶的活性。此外，它通过降低脂质过氧化和一氧化氮的产生，同时增加乙酰胆碱酯酶的活性，减轻神经元损伤。它改善了 HO 暴露引起的游泳行为变化和认知损伤。为了进一步证实 KK14 的神经保护潜力，评估了斑马鱼幼虫的细胞内 ROS 水平。这导致 ROS 水平降低和脂质过氧化减少。KK14 上调了抗氧化基因以应对氧化应激。总的来说，这项研究证明了 KK14 具有强大的抗氧化活性，表明其作为治疗氧化应激引起的神经紊乱的有效治疗选择的潜力。
