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.

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.

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