Tanshinone IIA loaded chitosan nanoparticles decrease toxicity of β-amyloid peptide in a Caenorhabditis elegans model of Alzheimer's disease

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases that characterized by the accumulation of β-amyloid peptide (Aβ). Overexpressions of Aβ could induce oxidative stress that might be a key insult to initiate the cascades of Aβ accumulation. As a result, anti-oxidative stress and attenuating Aβ accumulation might be one promising intervention for AD treatment. Tanshinone IIA (Tan IIA), a major component of lipophilic tanshinones in Danshen, is proven to be effective in several diseases, including AD. Due to the poor solubility in water, the clinical application of Tan IIA was limited. Therefore, a great number of nanoparticles were designed to overcome this issue. In the current study, we choose chitson as delivery carrier to load Tanshinone IIA ([email protected] IIA) and explore the protective effects of [email protected] IIA on the CL2006 strain, a transgenic C. elegans of AD model organism. Compared with Tan IIA monomer, [email protected] IIA could significantly prolong the lifespan and attenuate the AD-like symptoms, including reducing paralysis and the Aβ deposition by inhibiting the oxidative stress. The mechanism study showed that the protection of [email protected] IIA was attenuated by knockdown of daf-16 gene, but not skn-1. The results indicated that DAF-16/SOD-3 pathway was required in the protective effects of [email protected] IIA. Besides DAF-16/SOD-3 pathway, the Tan IIA-loaded CS nanoparticles might protect the C. elegans against the AD insults via promoting autophagy. All the results consistently suggested that coating by chitosan could improve the solubility of Tan IIA and effectively enhance the protective effects of Tan IIA on AD, which might provide a potential drug loading approach for the hydrophobic drugs as Tan IIA.