Tangeretin Supplementation Mitigates the Aging Toxicity Induced by Dietary Benzo[a]pyrene Exposure with Aberrant Proteostasis and Heat Shock Responses in Caenorhabditis elegans.

Benzo[a]pyrene (BaP) is a common food contaminant that can impair organismal aging. Tangeretin (TAN) may mitigate aging toxicities as a dietary supplement. This study used Caenorhabditis elegans to investigate the effects of chronic exposure to BaP on aging and to determine whether TAN supplementation could alleviate BaP-induced toxicity. Early life exposure to BaP (10 µM) significantly inhibited growth by 5%, and exposure to 0.1 to 10 µM BaP impaired C. elegans motility, resulting in a 3.4-6.5% reduction in motility. Chronic exposure to BaP (10 µM) age-dependently aggravated aberrant protein aggregation (7% increase) and shortened the median lifespan of the worms from 20 to 16 days. In addition, BaP worsened the age-dependent decline in motility and pharyngeal pumping, as well as the accumulation of reactive oxygen species. Furthermore, exposure to BaP resulted in significantly higher relative transcript levels of approximately 1.8-2.0-fold for the hsp-16.1, hsp-16.2, hsp-16.49, and hsp-70 genes. Stressed worms exposed to BaP exhibited significantly lower survival under heat stress. Dietary TAN supplementation alleviated the BaP-induced decline in motility, pumping, and poly-Q accumulation and restored heat shock proteins' transcript levels. Our findings suggest that chronic BaP exposure adversely affects aging and that TAN exposure mitigates the BaP-induced aging toxicity.

Prevention of Glutamate-Induced Neurodegeneration by Piceatannol via Mitochondrial Rescue In Vitro and In Vivo.

SCOPE: Parkinson's disease is one of the neurodegenerative diseases that have no cure. Excitotoxicity induced by excess glutamate is known to be a hallmark of these diseases. Therefore, this study aims to evaluate the preventive effect of piceatannol on glutamate-induced neurodegeneration via mitochondrial rescue. METHODS AND RESULTS: The PC12 cell line and three Caenorhabditis elegans (C. elegans) strains are employed to achieve the aim. In the in vitro study, the results show that piceatannol can prevent glutamate-induced apoptosis. Piceatannol also reduces mitochondrial reactive oxygen species (ROS) accumulation by activating the antioxidant system. Moreover, piceatannol can also promote mitochondrial biogenesis and induced mitochondrial fusion-related genes to preserve mitochondrial functionality. In the C. elegans model, piceatannol can prevent mitochondrial fragmentation induced by glutamate. More importantly, piceatannol effectively protects dopaminergic neurons from degradation and preserves the responses controlled by these neurons. CONCLUSION: The findings suggest that piceatannol can be a more effective and potent candidate for the treatment of neurodegenerative diseases, such as Parkinson's disease, compared to resveratrol. It is capable of preventing neurodegeneration induced by excess glutamate, possibly via mitochondrial rescue. It is recommended that piceatannol be developed into a neuroprotective agent.