Supplementary Material for: Curcumin Derivatives as Allosteric Modulator of Α7-Nachr: Functional and Molecular Docking Insights

Background: Curcumin has emerged as promising candidate for therapeutic modulation of neurodegenerative disorders by acting on α7-nicotinic acetylcholine receptors (α7-nAChR). Objective: This study aims to evaluate the potential of Curcumin metabolites and derivatives as positive allosteric modulators (PAMs) of α7-nAChR. Materials and Methods: Functional properties of α7-nAChR were assessed using two-electrode voltage clamp techniques in Xenopus oocytes, and molecular docking studies were employed to identify high-affinity binding sites. Results: The findings reveal that Curcumin metabolites and derivatives also potentiate α7-nAChR and interact with a common transmembrane domain binding site on α7-nAChR, demonstrating potent modulatory effects. Notably, these derivatives exhibit superior binding energies compared to the established PAM PNU-120596. Conclusion: The study underscores the therapeutic potential of Curcumin metabolites and derivatives as receptor-specific natural agents for managing neurodegenerative and inflammatory diseases.

研究背景：姜黄素可通过靶向α7烟碱型乙酰胆碱受体（α7-nicotinic acetylcholine receptors，α7-nAChR）发挥神经退行性疾病的治疗调节作用，已成为颇具前景的候选治疗药物。
研究目的：本研究旨在评估姜黄素代谢物及其衍生物作为α7-nAChR正变构调节剂（positive allosteric modulators, PAMs）的应用潜力。
材料与方法：采用双电极电压钳技术对非洲爪蟾卵母细胞中的α7-nAChR功能特性进行检测，并通过分子对接实验鉴定其高亲和力结合位点。
研究结果：结果显示，姜黄素代谢物及其衍生物同样可增强α7-nAChR活性，并与该受体上的保守跨膜结构域结合位点相互作用，展现出强效的调节作用。值得注意的是，相较于已确立的正变构调节剂PNU-120596，此类衍生物展现出更优的结合能。
研究结论：本研究凸显了姜黄素代谢物及其衍生物作为受体靶向天然制剂，在治疗神经退行性疾病与炎症性疾病方面的治疗潜力。