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源自天然分子(单宁酸和赖氨酸)的纳米凝胶对阿尔茨海默病的乙酰胆碱酯酶抑制能力

AChE Inhibition Capability of Nanogels Derived from Natural Molecules: Tannic Acid and Lysine for Alzheimer's Disease.

作者信息

Sahiner Mehtap, Suner Selin S, Sahiner Nurettin

机构信息

Department of Bioengineering, Faculty of Engineering, Canakkale Onsekiz Mart University, Terzioglu Campus, Canakkale 17100, Türkiye.

Department of Chemistry, Faculty of Sciences, Canakkale Onsekiz Mart University, Terzioglu Campus, Canakkale 17100, Türkiye.

出版信息

Pharmaceutics. 2025 Apr 10;17(4):502. doi: 10.3390/pharmaceutics17040502.

Abstract

Tannic acid (TA), a known natural polyphenolic acid with many bioactivities including antioxidants, antibacterial, and antiviral, can be combined with a natural essential amino acid L-lysine (LYS) in nanogel formulations to produce p(TA-co-LYS) (p(TA-co-LYS)) nanogels. : A 1:1 mole ratio of TA:LYS was used to prepare corresponding spherical nanogels employing formaldehyde as a linker via the Mannich reaction. : The attained p(TA-co-LYS) particles were in 283 ± 57 nm size ranges (via SEM analysis) and possessed smooth surfaces. The zeta potential measurements of p(TA-co-LYS) nanogels suspension at different solution pHs revealed the isoelectric point (IEP) of pH 4.9, suggesting that the particles are negatively charged at the physiological pH range (e.g., at 7.4). In addition to the antioxidant efficacy of nanogels confirmed by three different tests, p(TA-co-LYS) particles showed significant Fe(II) ion chelating capacity at 350 µg/mL concentrations compared to bare TA, which is 21%, whereas the LYS molecule had a chelating capacity of 100% at the same concentrations. Moreover, it was found that p(TA-co-LYS) nanogels inhibited the Acetylcholinesterase enzyme (AChE) at a concentration-dependent profile, e.g., at 333 µg/mL concentration of p(TA-co-LYS), 57.2% of the enzyme AChE activity was inhibited. Furthermore, the minimum inhibition concentrations of p(TA-co-LYS) nanogels of Gram-negative (ATCC 8739) and Gram-positive (ATCC 6538) were determined as 12.5 mg/mL. : As cytotoxicity studies of p(TA-co-LYS) nanogels on L929 fibroblast cells also ascertained that these particles can be safely used in many biomedical applications, including antioxidant materials, drug delivery devices, and enzyme inhibitors.

摘要

单宁酸(TA)是一种已知的天然多酚酸,具有多种生物活性,包括抗氧化、抗菌和抗病毒作用。它可以与天然必需氨基酸L-赖氨酸(LYS)在纳米凝胶制剂中结合,以制备p(TA-co-LYS)纳米凝胶。采用1:1的TA:LYS摩尔比,通过曼尼希反应,以甲醛作为连接剂制备相应的球形纳米凝胶。所得到的p(TA-co-LYS)颗粒尺寸范围为283±57nm(通过扫描电子显微镜分析),表面光滑。不同溶液pH下p(TA-co-LYS)纳米凝胶悬浮液的zeta电位测量显示等电点(IEP)为pH 4.9,这表明在生理pH范围(如7.4)内颗粒带负电荷。除了通过三种不同测试证实的纳米凝胶的抗氧化功效外,与纯TA相比,p(TA-co-LYS)颗粒在350μg/mL浓度下显示出显著的Fe(II)离子螯合能力,为21%,而LYS分子在相同浓度下的螯合能力为100%。此外,发现p(TA-co-LYS)纳米凝胶以浓度依赖性方式抑制乙酰胆碱酯酶(AChE),例如,在p(TA-co-LYS)浓度为333μg/mL时,57.2%的AChE酶活性受到抑制。此外,p(TA-co-LYS)纳米凝胶对革兰氏阴性菌(ATCC 8739)和革兰氏阳性菌(ATCC 6538)的最小抑制浓度测定为12.5mg/mL。p(TA-co-LYS)纳米凝胶对L929成纤维细胞的细胞毒性研究也确定,这些颗粒可安全用于许多生物医学应用,包括抗氧化材料、药物递送装置和酶抑制剂。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90aa/12030174/62358bd3b3bf/pharmaceutics-17-00502-g001.jpg

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