Cryptotanshinone downregulates the profibrotic activities of hypertrophic scar fibroblasts and accelerates wound healing: A potential therapy for the reduction of skin scarring

Hypertrophic scar (HS) is a skin fibrotic disease that causes major clinically problematic symptoms. Cryptotanshinone (CT) is an important ingredient of Danshen (Salvia miltiorrhiza Bunge extract) that has been used to treat cardio-cerebral vascular diseases. Its clinical efficacy in HS remains unclear. To investigate whether CT can inhibit HS fibrosis, HS-derived fibroblastic cells (HSFs) were established and treated with or without CT. Type-collagen-I (Col1), type-collagen-III (Col3) and α-smooth muscle actin (α-SMA) expression were measured by western blot and real-time quantitative polymerase chain reaction. HSFs migration and contraction were assessed with the scratch assay and the fibroblast-populated collagen lattice (FPCL) contraction assay, respectively. Wound healing in CT-treated Balb/c mice was assessed by immunohistochemical analysis of collagen expression and Masson’s trichrome staining analysis of collagen deposition. CT treatment of HSFs down-regulated Col1, Col3 and α-SMA mRNA and protein expression, HSFs migration, and HSFs contraction, and improved FPCL architecture. In mice, CT treatment accelerated wound healing: the scar margins were narrow and there was less collagen deposition in the regenerated tissue. Thus, CT promotes wound healing and decreases excessive deposition of extracellular matrix components. CT may help to prevent and reduce scarring.