Chlorpheniramine maleate exerts an anti-keloid activity by regulation of IL-6/JAK1/STAT3 signaling pathway

Keloids are abnormal scars formed due to fibroblast dysfunction and excessively deposited extracellular matrix (ECM). Despite the unclear process leading to the occurrence of keloids, several studies have demonstrated that histamine and its H1 receptor can effectively regulate fibroblast functions, contributing to keloid formation. Chlorpheniramine maleate (CPM) as a first-generation H1 antihistamine has been widely applied in symptomatic treatment of allergic conditions but its effects on keloids are unknown. This study holds the objective of exploring its effect on keloids. Cell Counting Kit-8 (CCK-8), apoptosis, cell cycle and migration assays were conducted to determine the effects of CPM on human keloid fibroblasts (KFs), with its therapeutic effect evaluated by constructing a keloid model in nude mice. RNA sequencing analysis, ELISA, western blotting and immunohistochemistry assisted in examining the anti-keloid mechanism of CPM. It was observed that CPM inhibited the proliferation and migration of KFs, promoted apoptosis of KFs, and blocked the G0/G1 phase of KFs. Moreover, local intralesional injection of CPM into nude mice keloid model significantly reduced keloid scars. According to RNA sequencing analysis, the gene expression of IL-6 and JAK-STAT signaling pathway were both negatively related in CPM group versus the control group. According to the in vivo and vitro experiment results, the anti-keloid activity of CPM was attributed to its inhibitory effect on the IL-6/JAK1/STAT3 signal pathway. In summary, CPM holds great potential for localized treatment of keloids.