Protective Effect and Mechanism of Fruit Extract of Aegle marmelos Against Amyloid-β Toxicity in a Transgenic Caenorhabditis elegans

Alzheimer's disease (AD) is the most common form of dementia found in the elderly. AD is caused by the accumulation of toxic proteins including amyloid-beta (A beta). The purpose of this study was to investigate the effect of fruit extract of Aegle marmelos against A beta toxicity in Caenorhabditis elegans. The fruit of A. marmelos has been used in a traditional Thai herb formula in fatigue patients recovering from illnesses such as fever and diarrhea. We used a transgenic C. elegans strain CL4176, which expresses the human A beta 42, to investigate the effects and the mechanisms of action of the extracts against A beta toxicity. The extract of A. marmelos significantly delayed A beta-induced paralysis. Aegle marmelos lost the ability to delay A beta-induced paralysis in worms fed with daf-16 ribonucleic acid interference (RNAi) bacteria, but not in worms fed with hsf-1 and skin-1 RNAi bacteria. These results indicated that daf-16 transcription factor was required for A. marmelos-mediated delayed paralysis. Aegle marmelos enhanced the level of daf-16 gene. Taken together, these results indicated that A. marmelos reduced A beta toxicity via the DAF-16-mediated cell signaling pathway. In addition, A. marmelos reduced toxic A beta oligomers. Aegle marmelos also displayed antioxidative effect in in vivo as it enhanced resistance to paraquat-induced oxidative stress in wild type worms. All of the results suggested that A. marmelos can protect against A beta-induced toxicity and can be a potential candidate for the prevention or treatment of AD.