Gallic acid alleviates exercise-induced muscle damage by inhibiting mitochondrial oxidative stress and ferroptosis.
Likai Yu, Di Tian, Zishan Su, Li Zhang, Shaobo Guo, Wenhui Zhu, Yuan Fang, Peimin Wang, Nongshan Zhang
Author Information
Likai Yu: Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine / Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, China.
Di Tian: Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine / Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, China.
Zishan Su: Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine / Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, China.
Li Zhang: Orthopedics of Traditional Chinese Medicine, Zhongda Hospital Southeast University, Nanjing, Jiangsu, 210009, China.
Shaobo Guo: Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.
Wenhui Zhu: Key Laboratory for Metabolic Diseases in Chinese Medicine, First College of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.
Yuan Fang: Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine / Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, China.
Peimin Wang: Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine / Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, China.
Nongshan Zhang: Department of Orthopedics, Affiliated Hospital of Nanjing University of Chinese Medicine / Jiangsu Province Hospital of Chinese Medicine, Nanjing, Jiangsu, 210029, China. zns0032@163.com. ORCID
BACKGROUND: Skeletal muscle injury caused by excessive exercise is one of the most commonly seen clinical diseases. It is indispensable to explore drugs for treating and relieving skeletal muscle injury. Gallic acid (GA) is a polyphenolic extract that has anti-inflammatory and antioxidant biological activities. However, its function and mechanism in skeletal muscle injury remain unclear. METHODS: We first established a skeletal muscle injury model caused by excessive exercise. Histopathological analysis was used to determine the severity of skeletal muscle injury in mice. Techniques such as ELISA, Western blot, and RT-qPCR were used to measure skeletal muscle injury markers including CK, LDH, IL-6, TNF-α, and ferroptosis-related indicators such as Fe, MDA, COX2, and GPX4. Transmission electron microscopy was used to observe the morphology of mitochondria. JC-1, DHE, and C11-BODIPY 581/591 probes were used to detect mitochondrial membrane potential, mitochondrial reactive oxygen species (mtROS), and lipid peroxidation levels. RESULTS: The results of this study indicate that GA has a positive therapeutic effect on skeletal muscle inflammation and injury induced by excessive exercise. On the one hand, GA can alleviate skeletal muscle mitochondrial injury and redox imbalance by reducing mitochondrial membrane potential level and increasing ATP production. On the other hand, GA can inhibit ferroptosis in skeletal muscle cells induced by excessive exercise through its antioxidant and anti-iron accumulation ability. CONCLUSIONS: In summary, GA protects against skeletal muscle injury induced by excessive exercise by inhibiting mitochondrial oxidative stress and ferroptosis pathways, providing new evidence for GA as a promising therapeutic agent for skeletal muscle injury.
