Acute soft tissue injury (ASTI), a common exercise-related condition, significantly impacts health and function. Its core pathology is inflammation, presenting with symptoms such as edema, pain, bruising, and functional impairment (Zhang et al., 2019; Clebak et al., 2023). The initial trauma triggers a local inflammatory response characterized by the rapid release of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), which recruit immune cells and amplify tissue damage. Concurrently, oxidative stress ensues from the generation of reactive oxygen species (ROS), and leads to lipid peroxidation and further cellular injury (Wang et al., 2024). In traditional Chinese medicine, acute soft tissue injuries are classified as "tendon injuries". The fundamental pathogenesis involves qi stagnation and blood stasis (Zhu et al., 2024). This key TCM syndrome describes a pathological state of impaired local microcirculation and energy dynamics, which lead to inflammation, hypoxia, pain, and dysfunctional tissue repair. This concept closely aligns with the modern understanding of the acute injury microenvironment, and thereby provides the traditional rationale for therapeutic strategies aimed at promoting blood circulation and resolving stasis (Cheng et al., 2025).

Safflower washing medicine (SWM) (Clinical Batch Number: Z20220701), as a drug for treatment of soft tissue injury, has been clinically applied for over twenty years. The principle of its combination is based on "Taohong Siwu Decoction" and "Qili san" in "Golden Mirror of Medicine" to promote blood circulation and relax the meridians (Shi et al., 2024; Tan et al., 2013). At the same time, it refers to "Ru Yi Jinhuang powder" in "Orthodox Manual of External Medicine" to reduce swelling and resolve lumps (Li et al., 2022). In clinical applications, it improves local blood stasis, swelling, limits mobility, and has good safety. It embodies the treatment concept of "treating both qi and blood, and harmonizing muscles and bones" in traditional Chinese medicine. SWM composed of Carthamus tinctorius L (Chinese name: “Hong hua”), Angelica dahurica (Chinese name: “Bai zhi”), Clematis chinensis Osbeck (Chinese name: “Weilingxian”), Boswellia sacra (Chinese name: “Ru xiang”), Commiphora myrrha (Nees) Engl (Chinese name: “Mo yao”) and other 6 Chinese medicine. The plant name has been verified with WFO (http://www.worldfloraonline.org) (Access date: 2025-11-11).

Hong hua serving as the monarch drug due to its blood-activating and stasis-resolving properties (Zhang et al., 2024). Its main active ingredient like hydroxysafflor yellow A(HSYA) alleviates the inflammatory response of thrombosis, significantly scavenges OH-free radicals, and promotes the repair and healing of vascular anastomosis (Ni et al., 2006). Three minister drugs augment its therapeutic effects. For example, Bai zhi eliminates wind-dampness (Xu et al., 2021). It mainly contains coumarin components like isoimperatorin, and has antipyretic, analgesic, anti-inflammatory, anti-pathogenic microbial, and cell growth-promoting effects (Qu et al., 2005). Momordica cochinchinensis (Lour.) Spreng (Chinese name: “Mubiezi”) reduces swelling and dissipates nodules, while Weilingxian dispels wind-dampness, promotes meridian circulation, relieves pain and displays antibacterial effects. Four assistant drugs further enhance the formula's efficacy. Taken an example, Angelica sinensis (Oliv.) Diels (Chinese name: “Dang gui”) promotes blood circulation and relieves pain. Lycopodium japonicum Thunb. (Chinese name: “Shenjincao”) eliminates wind dampness and relaxes tendons. Ru xiang and Mo yao display analgesia and stasis-relieving effects. Three guide drugs complete the formulation. Chaenomeles speciosa (Sweet) Nakai (Chinese name: “Mu gua”), and Ligusticum chuanxiong Hort (Chinese name: “Chuan xiong”) regulate qi-blood and relieve pain, while Zanthoxylum bungeanum Maxim (“Hua jiao”) warms analgesia for wind-cold-damp arthralgia. This hierarchical composition demonstrates a multi-target approach that contains blood activation, stasis resolution, and wind-dampness elimination for management of trauma (Ye, 2009).

Despite the extensive use of SWM in the treatment of soft tissue injuries in clinical practice, its underlying mechanisms are still not fully understood. This article established three mice models including toe swelling model, formalin-induced model and heavy impact-induced soft tissue injury to confirm the therapeutic and restorative effect of SWM. Through network pharmacology, the effect of the drug in achieving recovery through the PI3K-Akt signaling pathway was predicted and verified.