Alzheimer’s disease (AD) is one of the leading causes of dementia. As the first common neurodegenerative disease, there are no effective drugs that can reverse the progression. The present study is to report the anti-AD effect of cryptotanshinone (CTS), a natural product isolated from Salvia castanea. It is found that it can alleviate AD-like features associated with Aβ1-42 toxicity in muscle cells as well as neuronal cells of Caenorhabditis elegans (C. elegans). Further studies showed that CTS reduced the level of reactive oxygen species (ROS) in nematodes, up-regulated the expression of sod-3, and enhanced superoxide dismutase activity. Cryptotanshinone reduced the level of Aβ monomers and highly toxic oligomers in C. elegans while inhibiting the abnormal aggregation of polyglutamine protein. In addition, CTS upregulated the expression of hsp-16.2 and downregulated the expression of ace-2. These results suggested that CTS could alleviate oxidative stress and reduce the level of abnormally aggregated proteins and has the potential to be developed as an anti-AD drug candidate.
Alzheimer’s disease (AD) is the most prevalent neurodegenerative disease in the world. However, there is no effective drug to cure it. Caesalmin C is a cassane-type diterpenoid abundant in Caesalpinia bonduc (Linn.) Roxb. In this study, we investigated the effect of caesalmin C on Aβ-induced toxicity and possible mechanisms in the transgenic Caenorhabditis elegans AD model. Our results showed that caesalmin C significantly alleviated the Aβ-induced paralysis phenotype in transgenic CL4176 strain C. elegans. Caesalmin C dramatically reduced the content of Aβ monomers, oligomers, and deposited spots in AD C. elegans. In addition, mRNA levels of sod-3, gst-4, and rpt-3 were up-regulated, and mRNA levels of ace-1 were down-regulated in nematodes treated with caesalmin C. The results of the RNAi assay showed that the inhibitory effect of caesalmin C on the nematode paralysis phenotype required the DAF-16 signaling pathway, but not SKN-1 and HSF-1. Further evidence suggested that caesalmin C may also have the effect of inhibiting acetylcholinesterase (AchE) and upregulating proteasome activity. These findings suggest that caesalmin C delays the progression of AD in C. elegans via the DAF-16 signaling pathway and that it could be developed into a promising medication to treat AD.
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