海洋真菌抗老年痴呆相关活性成分的筛选与追踪研究

Screening and Tracing of Anti-alzheimer Related Bioactive Constituents from Marine Fungi

摘要:

本文作者对44株海洋真菌的抗老年痴呆相关活性成分进行了筛选与追踪。采用DTNB法和DPPH自由基清除法分别评价其提取物抑制乙酰胆碱酯酶（AChE）和抗氧化活性，采用生物自显影和专一性显色剂分析活性物质多样性及结构类型，采用高分辨液质联用分析代表性菌株的活性代谢产物。发现共计32株菌在不同培养基中的发酵产物，显示了显著的双重活性，它们来自不同真菌类群。生物自显影显示它们可产生多样化活性成分，化学显色显示其活性成分可能为生物碱等含氮化合物、酚类及其他结构类型的天然产物。通过液质联用分析，发现一株真菌中分子式为C16H13NO2的代谢产物具有较强抑制AChE活性。本研究表明海洋真菌是多样化抗老年痴呆活性物质的重要来源，为活性物质的后续分离鉴定奠定了基础。

Abstract:

Active constituents having anti-Alzheimer’s effects were screened and traced in 44 marine fungal strains. Acetylcholinesterase (AChE) inhibitory and antioxidant activities were assessed using the 5,5-dithio-bis-2-nitrobenzoic acid method and the 1,1-diphenyl-2-picrylhydrazyl (DPPH) free-radical scavenging method, respectively. Bioautography and specific color-developing reagents were applied to investigate the diversity of bioactive substances and their structural types, respectively. HPLC-Q-TOF-ESI-HRMS was used to characterize representative fungal bioactive metabolites. The fermentation extracts of 32 strains in different culture media showed remarkable dual bioactivity against AChE and DPPH. These dual-bioactive strains originated from different fungal taxa. Bioautography revealed their diverse bioactive constituents. Chemical colorization further suggested that their active components were nitrogenated compounds (alkaloids), phenols, and other types of natural products. Based on HPLC-Q-TOF-ESI-HRMS analysis, a metabolite with molecular formula C16H13NO2 of a strain exhibited relatively strong inhibition effect against AChE. The present study revealed that marine fungi were an important source of diverse anti-Alzheimer’s active substances, and provided a foundation for future studies involving the isolation and elucidation of bioactive compounds.