The Effect of ZHSJ Ointment on Hypertrophic Scar in the Rabbit Ear Model

INTRODUCTION: Hypertrophic scars (HS), resulting from excessive fibroblast activity and abnormal extracellular matrix buildup after skin injuries, affect appearance and quality of life, often causing itching. Despite limited treatment success, Traditional Chinese Medicines (TCM) may enhance wound healing. This study examines the effects and therapeutic mechanisms of Zihuang Shengji Ointment (ZHSJ) on HS. METHODS: A rabbit ear HS model was initially developed, showing red, elevated scars with hyperplasia and firm texture at 28 days post-operation. HE and VG staining assessed ZHSJ's effects on pathological changes, while western blot and qRT-PCR evaluated specific protein and mRNA expression levels. RESULTS: Our study found that ZHSJ effectively reduces scar formation in rabbit ears, with the medium concentration being the most effective. ZHSJ inhibits angiogenesis, irregular fibroblast formation, and disordered collagen fiber arrangement. It also suppresses fibroblast proliferation, lowers collagen I, collagen III, and TGF-β1 levels, and increases MMP1 and TIMP1 expression. ZHSJ significantly inhibits p38 and MK2 activation; importantly, the p38 activator Anisomycin reverses the anti-scarring effects of ZHSJ, confirming that ZHSJ reduces collagen synthesis and promotes collagen degradation in HS through the p38/MK2 pathway. CONCLUSION: In summary, evidence from studies on multi-component TCM formulations and molecular pathways supports ZHSJ's potential as a therapeutic TCM for HS.