Chlorpheniramine maleate exerts an anti-keloid activity in vivo and in vitro

Abstract Background: Keloid can cause numerous adverse consequences, severely affecting patients' physical and mental health. The mechanisms of keloid scarring remain unclear, as revealed by the inability of patients to satisfactorily manage this benign neoplastic disease. Studies suggest that H1 blockers, such as Tranilasts, inhibit keloid overgrowth and hyperplasia. Chlorpheniramine maleate (CPM) has been extensively employed as an H1 receptor blocker, whereas its treatment effects on keloid formation are unknown. The present study aimed to evaluate the inhibiting effect of CPM on keloid, which might provide a novel strategy for keloid treatment. Methods: In vitro , Cell Counting Kit-8 (CCK-8), apoptosis, cell cycle and migration assays of keloid fibroblasts (KFs) were performed to evaluate the effects of CPM on inhibiting the proliferation and apoptosis of dermal fibroblasts (DFs) and keloid fibroblasts (KFs), and the potential mechanism of action was analyzed by qPCR. In vivo , nude mice keloid scar model was built to assess the therapeutic effect of CPM and explore its possible mechanism. Results: CCK-8 and apoptosis experiments revealed that the concentration of 0.15 mM CPM could inhibit keloid fibroblasts proliferation and promote apoptosis with minimal impact on DFs. Cell cycle and migration experiments confirmed that a 0.15 mM CPM could inhibit the proliferation and migration of keloid fibroblasts. Moreover, qPCR revealed that CPM down-regulated the expressions of TGF-β, STAT3, JAK1, and Ki-67 genes in KFs. Together with in vitro experiments, CPM could inhibit keloid scar formation and down-regulate the expressions of TGF-β, STAT3, JAK1, and Ki-67 genes in the tissue. Conclusion: Chlorpheniramine maleate could be an ideal localized therapeutic strategy in keloid treatment.