Zhang Qiaoju, Luo Xi, Zheng Yuwen, Zheng Junqiao, Wu Xinying, Shi Jun
School of Chinese Materia Medica, Guangdong Pharmaceutical University of China, Guangzhou Higher Education Mega Center, Guangzhou 510006, China.
Foshan Traditional Chinese Medicine Hospital Affiliated to Guangzhou University of Chinese Medicine, Foshan 528000, Guangdong, China.
Toxicol Appl Pharmacol. 2025 Jun;499:117339. doi: 10.1016/j.taap.2025.117339. Epub 2025 Apr 9.
Hypertrophic scars (HS) affect up to 70 % of individuals following deep dermal injuries, burns, or surgical procedures, leading to significant functional impairments and psychological distress. Despite their high prevalence, effective therapeutic options remain limited, and the underlying pathophysiology is not fully elucidated. This study integrates network pharmacology, molecular docking, and in vivo experimentation to investigate the therapeutic potential of total salvianolic acid (TSA) from Salvia miltiorrhiza in HS treatment. A systematic pharmacology approach identified 186 target proteins, highlighting TGF-β1, Smad3, IL-2, and IL-4 as key modulators of fibrosis and inflammation. Molecular docking confirmed high-affinity interactions between TSA's active components and these targets. TSA significantly reduced scar elevation, fibrosis, and collagen deposition in a rabbit ear hypertrophic scar model, restoring tissue architecture and improving hemorheological parameters. Histological and immunohistochemical analyses confirmed TSA's ability to suppress TGF-β/Smad signaling, downregulate inflammatory cytokines and normalize collagen dynamics. These findings provide compelling evidence that TSA is a multi-targeted, pharmacologically active compound with promising anti-fibrotic and microcirculatory benefits, paving the way for novel therapeutic strategies in HS management. This study establishes a scientific foundation for TSA-based interventions, with potential clinical implications in regenerative medicine and scar therapy.
肥厚性瘢痕（HS）在深度真皮损伤、烧伤或外科手术后影响高达70%的个体，导致严重的功能障碍和心理困扰。尽管其发病率很高，但有效的治疗选择仍然有限，其潜在的病理生理学尚未完全阐明。本研究整合网络药理学、分子对接和体内实验，以研究丹参总酚酸（TSA）在HS治疗中的治疗潜力。一种系统药理学方法确定了186种靶蛋白，突出了转化生长因子-β1（TGF-β1）、Smad3、白细胞介素-2（IL-2）和白细胞介素-4（IL-4）作为纤维化和炎症的关键调节因子。分子对接证实了TSA活性成分与这些靶点之间的高亲和力相互作用。在兔耳肥厚性瘢痕模型中，TSA显著降低了瘢痕隆起、纤维化和胶原沉积，恢复了组织结构并改善了血液流变学参数。组织学和免疫组织化学分析证实TSA能够抑制TGF-β/Smad信号传导，下调炎性细胞因子并使胶原动态正常化。这些发现提供了令人信服的证据，表明TSA是一种具有多靶点、药理活性的化合物，具有有前景的抗纤维化和改善微循环的益处，为HS管理中的新型治疗策略铺平了道路。本研究为基于TSA的干预措施奠定了科学基础，在再生医学和瘢痕治疗中具有潜在的临床意义。
