# Obesity-Related Oxidative Stress and Antioxidant Properties of Natural Compounds in the Enteric Nervous System: A Literature Overview

## TL;DR

This paper reviews how obesity-related oxidative stress affects the gut's nervous system and how natural compounds may help reduce this damage.

## Contribution

The paper provides a comprehensive overview of the role of natural antioxidants in mitigating obesity-induced oxidative stress in the enteric nervous system.

## Key findings

- Obesity increases oxidative stress in the enteric nervous system through hyperglycemia and hyperlipidemia.
- Natural antioxidants and bioactive compounds can reduce oxidative and inflammatory damage in the gut.
- Enteric glial cells play a key role in mediating neuroinflammation under oxidative stress conditions.

## Abstract

The enteric nervous system (ENS) constitutes a highly organized and intricate neuronal network comprising two principal plexuses: myenteric and submucosal. These plexuses consist of neurons and enteric glial cells (EGCs). Neurons ensure innervation throughout the intestinal wall, whereas EGCs, distributed within the mucosa, contribute to epithelial barrier integrity and modulation of local inflammatory responses. The ENS orchestrates essential gastrointestinal functions, including motility, secretion, absorption, vascular regulation, and immune interactions with gut microbiota. Under physiological conditions, intestinal homeostasis involves moderate generation of reactive oxygen species (ROS) through endogenous processes such as mitochondrial oxidative phosphorylation. Cellular antioxidant systems maintain redox equilibrium; however, excessive ROS production induces oxidative stress, promoting EGCs activation toward a reactive phenotype characterized by pro-inflammatory cytokine release. This disrupts neuron–glia communication, predisposing to enteric neuroinflammation and neurodegeneration. Obesity, associated with hyperglycemia, hyperlipidemia, and micronutrient deficiencies, enhances ROS generation and inflammatory cascades, thereby impairing ENS integrity. Nevertheless, non-pharmacological strategies—including synthetic and natural antioxidants, bioactive dietary compounds, probiotics, and prebiotics—attenuate oxidative and inflammatory damage. This review summarizes preclinical and clinical evidence elucidating the interplay among the ENS, obesity-induced oxidative stress, inflammation, and the modulatory effects of antioxidant interventions.