# Protective Effects of Quinic Acid Against Disuse-Induced Skeletal Muscle Atrophy via Regulation of Inflammation and Oxidative Stress

## TL;DR

Quinic acid helps prevent muscle loss from disuse by reducing inflammation and oxidative stress, and improving muscle function in mice.

## Contribution

This study reveals quinic acid's novel ability to counteract disuse-induced muscle atrophy through multiple biological pathways.

## Key findings

- Oral quinic acid restored muscle weight and function in immobilized mice.
- Quinic acid reduced pro-inflammatory cytokines and E3 ubiquitin ligases in atrophic muscles.
- Quinic acid reactivated key signaling pathways for protein synthesis and myogenesis.

## Abstract

Disuse-induced muscle atrophy (DMA), commonly resulting from immobilization, is driven by chronic inflammation and oxidative stress, which disrupts the balance between protein synthesis and degradation. Quinic acid (QA), a natural compound with known antioxidant and anti-inflammatory properties, was investigated for its potential to counteract muscle atrophy. Using a DMA-induced immobilization model in male C57BL/6N (8 weeks) mice, we found that oral QA administration significantly restored the weight and cross-sectional area of atrophic muscles and improved muscle function, as measured by grip strength and treadmill performance. QA also reduced the expression of pro-inflammatory cytokines (Tnf, Il6, and Myostatin) and E3 ubiquitin ligases (Trim63 and Fbxo32), while increasing antioxidant enzyme levels and serum IL-15 in DMA. In tumor necrosis factor-α-stimulated L6 myotubes, QA reversed inflammation- and oxidative stress-induced gene changes, suppressed NF-ĸB activation, and downregulated protein degradation pathways mediated by FoxO3α. Furthermore, QA restored the expression of myogenesis-related genes and reactivated PI3K/Akt and mTOR/p70S6K/4EBP1 signaling pathways, enhancing protein synthesis. Collectively, our findings demonstrate that QA mitigates immobilization-induced muscle atrophy by modulating inflammation, oxidative stress, and key anabolic and catabolic signaling pathways. These results suggest that QA is a promising functional compound for preserving skeletal muscle health under conditions of disuse.