Safflower washing medicine alleviating acute soft tissue injury via PI3K/Akt pathway.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Safflower Wash Medicine (SWM) is an external traditional Chinese medicine prepared by percolation of safflower and ten other herbal materials. It has been clinically used to treat acute soft tissue injury (ASTI) for nearly two decades, and has shown a favorable safety profile. However, the underlying material basis of SWM in treating ASTI remains unclear. AIM OF THE STUDY: This study aimed to systematically investigate the anti-inflammatory and analgesic basis and mechanism of SWM in the treatment of soft tissue injuries. MATERIALS AND METHODS: The bioactive compounds in SWM were identified by UPLC-Triple TOF-MS/MS analysis. The pharmacological effects were evaluated in vivo using three animal models, such as carrageenan-induced paw edema, formalin-induced pain, and weight-drop-induced soft tissue injury. To elucidate the mechanism, an integrated approach combining network pharmacology and western blotting was employed. Furthermore, molecular docking was performed to assess the binding affinities between SWM's active components and key target proteins. RESULTS: A total of 40 bioactive compounds, including flavonoids, phenolic acids, and organic acids, were identified in SWM. In animal models, SWM significantly suppressed inflammatory swelling, reduced pain-related behaviors, promoted the regeneration of injured muscle fibers, and inhibited the release of pro-inflammatory cytokines like IL-6 and IL-1β. Molecular docking confirmed strong binding affinities between multiple active components of SWM and the key targets such as PI3K and Akt. CONCLUSION: This study demonstrates that SWM ameliorates soft tissue injury by activating the PI3K-Akt pathway and suppressing inflammatory responses. These findings provide, for the first time, a scientific basis for the clinical efficacy of SWM and support its broader application in treating ASTI.