Inhibition of Al(III)-Induced A β 42 Fibrillation and Reduction of Neurotoxicity by Epigallocatechin-3-Gallate Nanoparticles.

RATIONAL: Accumulation of amyloid beta fibrils is the pathological hallmark of Alzheimer's disease. Epigallocatechin-3-gallate (EGCG) has shown to possess potent anti-amyloidogenic, metal chelation and antioxidant properties. However, its therapeutic potential is limited in-vivo due to its poor bioavailability and stability. Therefore, the present study aims to evaluate the neuroprotective role of EGCG nanoparticles (nanoEGCG) against Al(III)-induced Aβ42 fibrillation in-vitro.

METHOD: NanoEGCG was synthesized and its physiochemical characterization was performed. In-vitro release profiles and stability of nanoEGCG in simulated gastro-intestinal fluids, along with its antioxidant and metal chelation potential was evaluated. The anti-amyloidogenic potential of nanoEGCG on Aβ42 secondary structure and its morphology was evaluated via induction with Al(III) and nanoEGCG treatment. Further, the effect of Aβ42 on cellular toxicity was also assessed.

RESULT: NanoEGCG with 96% encapsulation efficiency and a hydrodynamic diameter of 300 nm with spherical to slightly ellipsoid shape was synthesized. EGCG release from the nanoparticle occurred in a sustained manner and was stable when released in simulated gastro-intestinal fluids. The antioxidant and metal chelation potential of nanoEGCG over time was better than its free form. Effective inhibition of both Aβ42 and Al(III) induced Aβ42 fibrillation with nanoEGCG treatment was noted. This was achieved through the generation of soluble Aβ42 amorphous aggregates instead of insoluble Aβ42 oligomers and fibril generation. Significant reduction in cellular toxicity was also noted when treated with nanoEGCG.

CONCLUSION: In conclusion, this study strengthens the hypothesis that EGCG nanoparticles can inhibit Al(III)-induced Aβ42 fibrillation and its neurotoxicity in-vitro.