1,8-Cineole is a bicyclic monoterpene widely distributed in the essential oils of various medicinal plants, and it exhibits significant anti-inflammatory and antioxidant activities. We aimed to investigate the therapeutic effect of 1,8-cineole on anti-Alzheimer's disease by using transgenic Caenorhabditis elegans models. Our studies demonstrated that 1,8-cineole significantly relieved A β 1–42 -induced paralysis and exhibited remarkable antioxidant and anti-A β 1–42 aggregation activities in transgenic nematodes CL4176, CL2006 and CL2355. We developed a 1,8-cineole/cyclodextrin inclusion complex, displaying enhanced anti-paralysis, anti-A β aggregation and antioxidant activities compared to 1,8-cineole. In addition, we found 1,8-cineole treatment activated the SKN-1/Nrf-2 pathway and induced autophagy in nematodes. Our results demonstrated the antioxidant and anti-Alzheimer's disease activities of 1,8-cineole, which provide a potential therapeutic approach for Alzheimer's disease.
Screening Aβ aggregation inhibitors (AAIs) is important for Alzheimer's disease drug discovery. However, common cellular or biochemical methods are not suitable for high-throughput natural product screening. A gold nanoparticle (GNP) screening method was employed in this study to screen marine fungal crude extracts and pure compounds for quick AAI discovering. The anti-Aβ aggregation activity was further inspected using transmission electron microscopic (TEM) observation, and the interaction between active molecules and different Aβ species was revealed by molecular docking. The results indicated that the fungal extracts DLS2008001(M), BM3T2(M), DLEN2008005(M), TBG1-16(P), and TBG1-13(P) showed activity comparable to the positive control human serum albumin at the concentration of 500 µg/mL; 10 pure compounds also displayed moderate anti-aggregation activity, particularly nidulin, aspergillusidone G, and butyrolactone I. The inspection of anti-Aβ aggregation effect through TEM further demonstrated that extracts TBG1-16(P), DLS2008001(M), and BM3T2(M) dramatically inhibited the formation of Aβ aggregates. Molecular docking displayed low binding energies and key interactions of nidulin, aspergillusidone G, and butyrolactone I, with nine types of Aβ peptides. These findings indicate that the GNP method is efficient in screening AAIs and reveal marine fungal natural products as valuable sources of small molecular AAIs. Graphical GRAPHICAL
危险品化学品经营许可证（带存储）