Shamsi Anas, Shahwan Moyad, Zuberi Azna, Kundu Bishwajit, Khan Mohd Shahnawaz
Center for Medical and Bio-Allied Health Sciences Research, Ajman University, United Arab Emirates.
Center for Medical and Bio-Allied Health Sciences Research, Ajman University, United Arab Emirates; Department of Clinical Sciences, College of Pharmacy and Health Sciences, University, Ajman, United Arab Emirates.
Biomed Pharmacother. 2025 Jun;187:118101. doi: 10.1016/j.biopha.2025.118101. Epub 2025 Apr 29.
Lactoferrin (LTF), a multifunctional glycoprotein, plays a critical role in iron metabolism, host defense mechanisms, and the regulation of inflammatory pathways. It is widely present in various mammalian secretions, including saliva, tears, and nasal fluids, and exhibits potent antimicrobial, immunomodulatory, and neuroprotective properties. Emerging evidence suggests that LTF may be pivotal in mitigating neurodegenerative diseases (NDs) by modulating oxidative stress and neuroinflammation. This study investigates the interaction of LTF with Noscapine, a benzylisoquinoline alkaloid known for its therapeutic potential, including anticancer and neuroprotective effects. Fluorescence binding studies revealed a strong binding affinity between LTF and Noscapine with a binding constant (K) of 0.1 × 10 M. Circular dichroism (CD) spectroscopy revealed subtle changes in LTF's secondary structure and a strong binding affinity between LTF and Noscapine, indicative of specific molecular interactions and conformational adjustments. Additionally, in silico studies were performed to complement the experimental findings. Molecular docking studies identified potential binding sites and highlighted key interactions stabilizing the LTF-Noscapine complex. Molecular dynamic (MD) simulation studies demonstrated that structural compactness is well preserved with only minimal structural alterations observed in the protein upon binding of Noscapine. Together, these results provide comprehensive insights into the molecular basis of LTF-Noscapine interaction, with potential implications for therapeutic applications in NDs. This study lays the groundwork for further exploration of Noscapine's potential in combating NDs and other biomedical challenges.
乳铁蛋白（LTF）是一种多功能糖蛋白，在铁代谢、宿主防御机制以及炎症信号通路的调节中发挥着关键作用。它广泛存在于各种哺乳动物分泌物中，包括唾液、眼泪和鼻腔分泌物，并具有强大的抗菌、免疫调节和神经保护特性。新出现的证据表明，LTF可能通过调节氧化应激和神经炎症在减轻神经退行性疾病（NDs）方面发挥关键作用。本研究调查了LTF与诺斯卡品（一种以其治疗潜力而闻名的苄基异喹啉生物碱，包括抗癌和神经保护作用）之间的相互作用。荧光结合研究表明，LTF与诺斯卡品之间具有很强的结合亲和力，结合常数（K）为0.1×10 M。圆二色性（CD）光谱显示LTF二级结构有细微变化，且LTF与诺斯卡品之间具有很强的结合亲和力，这表明存在特定的分子相互作用和构象调整。此外，还进行了计算机模拟研究以补充实验结果。分子对接研究确定了潜在的结合位点，并突出了稳定LTF-诺斯卡品复合物的关键相互作用。分子动力学（MD）模拟研究表明，在诺斯卡品结合后，蛋白质的结构紧凑性得到了很好的保留，仅观察到最小的结构改变。总之，这些结果为LTF-诺斯卡品相互作用的分子基础提供了全面的见解，对NDs的治疗应用具有潜在意义。本研究为进一步探索诺斯卡品在对抗NDs和其他生物医学挑战方面的潜力奠定了基础。
