# Metabolites from chia seed (Salvia Hispanica L.) exert antioxidant effects through activation of the DAF-16 pathway and neuroprotective activity in the Caenorhabditis elegans model of Huntington’s disease

## TL;DR

Chia seed metabolites protect against Huntington's disease in worms by reducing oxidative stress and protein aggregates.

## Contribution

Identifies chia seed's neuroprotective effects in a Huntington's disease model via DAF-16 pathway activation and antioxidant activity.

## Key findings

- Chia seed extract increased worm survival and reduced ROS levels under oxidative stress.
- The DAF-16/FOXO pathway was activated, with upregulated SOD-3 and reduced HSP-16.2 expression.
- Chia seed reduced polyQ aggregation clusters linked to Huntington's disease.

## Abstract

Salvia hispanica L., chia seed, is a well-known highly nutritious nutraceutical normally included in the daily diet of many people worldwide. Despite having a plethora of reported beneficial uses, little is known about its neuroprotective properties, especially in Huntington’s disease (HD). In our study, we focused on testing the antioxidant properties of metabolites from chia (CH) seed and their potential to protect against the development of HD in the in vivo worm model, Caenorhabditis elegans (C. elegans).

Using the C. elegans model, the oxidative stress resistance capabilities were tested via a survival assay through exposure to a toxic dose of the pro-oxidant juglone. The antioxidant properties were assessed by performing ROS assay to detect the intracellular levels of basal ROS inside the worms. To detect whether the DAF-16/FOXO pathway is involved in the antioxidant activity or not, its activation with its downstream target genes, sod-3 and hsp-16.2, was tested. The neuroprotective activity against several HD-associated phenotypes was evaluated by assessing the number of polyQ150, polyQ35, and polyQ40 aggregation clusters. This study also comprehensively characterized the bioactive secondary metabolites profile of the dichloromethane (DCM) fraction of chia seed using UPLC–q-TOF–ESI–MS/MS.

In our study, CH seed DCM fraction was able to increase the survival of C. elegans worms exposed to juglone and could attenuate the basal ROS levels inside the worms. It was also able to activate the DAF-16/FOXO pathway through increasing its nuclear localization, upregulating the expression of SOD-3 and decreasing the expression of HSP-16.2 following juglone exposure. CH seed looks promising as an anti-HD candidate because of its ability to reduce the formation of polyQ35, polyQ40 and polyQ150 clusters. Finally, phytochemical profiling of the active DCM fraction identified seventy five metabolites belonging to various phytochemical classes.

This study shows that CH seed extract decreases oxidative stress and polyQ aggregates accumulation, associated with HD-related phenotypes, in a Caenorhabditis elegans model, supporting further investigations.