# Gypenosides mitigate acrylamide-induced oxidative stress, inflammation and lipid metabolic dysregulation in retinal pigment epithelial cells and in zebrafish embryos

## TL;DR

Gypenosides protect retinal cells and zebrafish embryos from acrylamide's harmful effects by reducing oxidative stress, inflammation, and lipid imbalances.

## Contribution

This study demonstrates gypenosides' protective effects against acrylamide toxicity in both human retinal cells and zebrafish embryos.

## Key findings

- Gypenosides reduced oxidative stress and restored antioxidant defenses in retinal pigment epithelial cells exposed to acrylamide.
- Gypenosides mitigated acrylamide-induced inflammation and lipid metabolism disruption in both cell and zebrafish models.
- Zebrafish embryos showed improved hatching and cardiac function with gypenoside co-treatment after acrylamide exposure.

## Abstract

Acrylamide (ACR) is an environmental and dietary contaminant widely known to induce imbalance in several biological systems, including oxidative stress, inflammation, and metabolic dysregulation. This study investigated the protective effects of gypenosides (GYP) against ACR-induced toxicity in human retinal pigment epithelial (RPE) cells and zebrafish embryos.

RPE cells and zebrafish embryos were treated with ACR, or ACR + GYP; the levels of reactive oxygen species (ROS), antioxidative enzymes, proinflammatory cytokines, and lipids were measured using biochemical approaches. Our findings demonstrate that ACR exposure significantly elevated ROS production, increased lipid peroxidation, suppressed antioxidant defences, and upregulated pro-inflammatory cytokines in RPE cells. Additionally, ACR disrupted lipid metabolism, significantly increasing cellular cholesterol, triglyceride, and phospholipid levels while altering cholesterol metabolism gene expression. Co-treatment with GYP effectively mitigated ACR-induced oxidative stress by normalising ROS levels, restoring antioxidant enzyme activities, and upregulating antioxidant gene expression. GYP also attenuated the ACR-triggered inflammatory response, significantly downregulating the expression of proinflammatory cytokine genes. Furthermore, GYP normalised lipid profiles and modulated lipid-related gene expression disrupted by ACR exposure. Parallel zebrafish experiments corroborated these protective effects. ACR exposure led to delayed hatching, impaired cardiac function, increased ROS production, and neutral lipid accumulation. These adverse effects were markedly ameliorated by GYP co-treatment, which reduced oxidative stress, downregulated proinflammatory markers, and restored lipid homeostasis.

The results highlighted that GYP, as a natural protective agent against ACR-induced cellular and metabolic toxicity in both in vitro and in vivo models, exhibited antioxidative, anti-inflammatory, and lipid-regulatory properties.

The online version contains supplementary material available at 10.1007/s11033-026-11676-3.