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 Fe²⁺, 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.

Background: External mechanical stress plays a pivotal role in the pathogenesis of knee osteoarthritis. Piezo1 can sense mechanical stress changes on the surface of various cell types and convert them into bioelectrical signals to regulate cellular functions. Therefore, our study aimed to investigate the role of Piezo1 in mechanically induced KOA and elucidate its underlying mechanisms. Methods: In this study, we employed various techniques to assess the effects of mechanical stress on knee joint cartilage in vivo and in vitro experiments. In vivo, we performed Micro-CT scanning, H&E staining, and ELISA analysis on the knee joints to evaluate the degree of cartilage damage and the expression of pro-inflammatory factors. In vitro, we utilized a cell stretcher to apply mechanical stress specifically to chondrocytes. Subsequently, we investigated the expression levels of Piezo1, pro-inflammatory factors, Collagen II, and other relevant markers within the chondrocytes. This approach aimed to shed light on the potential impact of Piezo1 on chondrocytes when subjected to mechanical stress. Results: Elevated expression of Piezo1 was observed in the cartilage of mice post-treadmill exercise intervention, with noticeable damage to the cartilage tissue and reduced surface smoothness. External mechanical stress significantly lowered the synthesis of the extracellular matrix in chondrocytes, potentially through the inhibition of mitochondrial autophagy levels, leading to increased mitochondrial dysfunction and the induction of pro-apoptotic proteins and pro-inflammatory cytokines. Conclusions: Mechanical stress induces extracellular matrix degradation and promotes KOA progression through Piezo1-mediated chondrocyte autophagy dysfunction and apoptotic injury.