Corilagin alleviates hypertrophic scars via inhibiting the transforming growth factor (TGF)-β/Smad signal pathway

Aims: Exploring the effects of corilagin on hypertrophic scar (HS) and its underlying mechanisms. Main methods: Human HS-derived fibroblasts (HSFs) were isolated and treated with corilagin. To investigate the effects of corilagin on HSFs, quantitative real time polymerase chain reaction (qRT-PCR), western blotting, wound healing, and immunofluorescence assays were performed. These effects were confirmed in a rabbit ear scar model by histological and immunohistochemical studies. Lastly, western blot assay was performed to detect the protein levels of several components of the transforming growth factor (TGF)-beta/Smad signaling pathway, as well as the protein levels of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs). Key findings: Corilagin showed multiple effects on HSFs, including does-dependent inhibition of collagen production, cell proliferation, and migration, besides suppression of the activation of HSFs. Moreover, corilagin suppressed HS formation and collagen deposition in a rabbit ear scar model. Corilagin also inhibited fibroblast proliferation and alpha-smooth muscle actin (alpha-SMA) expression in vivo. Finally, western blot analysis revealed that corilagin downregulated the protein levels of TGF-beta 1 and TGF-beta receptor type I (TGF beta RI), thus lowering the level of p-smad2/3, also affected the protein levels of MMPs and TIMP1. Significance: Corilagin could be a potential agent for HS treatment through the inhibition of extracellular matrix (ECM) deposition and multiple functions of fibroblasts.