Rosmarinic Acid Enhances Functional Recovery of Injured Muscle via Reducing Fibrosis and Enhancing Muscle Regeneration After Muscle Contusion.

Muscle contusion is the common injuries and present a challenge in traumatology. Nonsteroidal anti-inflammatory drugs (NSAIDs) relieve inflammation and pain after muscle injury, but the adverse effects including gastrointestinal bleeding and allergy are thorny problems. Therefore, it is imperative to develop safe and effective treatments. Rosmarinic acid (RA), an ester of caffeic acid, is first isolated from rosemary plant. It exhibits various biological activities, but its therapeutic potential on injured muscle remains unclear. In the study, we aimed to explore the effects of rosmarinic acid on skeletal muscle contusion. C57BL/6 mice were randomly assigned to control, injury, injury + diclofenac, and injury + RA groups. The injury of right gastrocnemius muscle was developed using a drop-mass method, and mice received phosphate-buffered saline (PBS), diclofenac (10 mg/kg BW), or rosmarinic acid (40 mg/kg BW) via intraperitoneal administration for 7 or 14 days after injury. Data revealed that rosmarinic acid treatment significantly decreased inflammatory response and collagen deposition in the injured muscles. And, rosmarinic acid treatment attenuated the levels of muscle damage markers (CK, LDH, and GOT) in serum after injury. In the injury + RA group, the levels of desmin, one of known myogenic marker, and the number of centrally nucleated myofibers, which are indicative of regenerating fibers, were both increased in injured muscle on day 7 after injury. Furthermore, rosmarinic acid treatment promoted recovery of locomotor abilities in the behavior analysis. Based on these findings, we suggested that rosmarinic acid treatment mitigated inflammatory responses to protect muscles from further damage, decreased fibrosis, enhanced muscle regeneration, and ultimately improved motor function recovery. Thus, RA may be potential drug for treating contusion-induced muscle injuries.