Jia-Wei-Si-Miao-Yong-An Fang stimulates the healing of acute radiation-induced cutaneous wounds through MAPK/ERK pathway

A famous traditional oral Chinese medicine formula, Si-Miao-Yong-An decoction, has been used to treat thromboangiitis obliterans from the Qing Dynasty. Because its therapeutic principles including clearing away heat, detoxification, accelerating blood circulation and relieving pains are consistent with acute radiation-induced cutaneous wounds in traditional Chinese medicine, we tried to add herbs and improve them into an external dosage form, called Jia-Wei-Si-Miao-Yong-An Fang (JWSMYA). However, its mechanism on radiation-induced cutaneous wounds is still unknown.This study evaluated the therapeutic effect of JWSMYA and investigated the mechanism of repair and anti-fibrosis on acute radiation-induced cutaneous wounds with JWSMYA.Firstly, we prepared JWSMYA, and determined the composition through UHPLC LC-MS/MS. Then we used ionizing radiation to make a cutaneous wound model of rats, and observed wound healing through their skin injury score, wound contraction percentage and histological staining. In addition, immunohistochemical staining, Western blot analysis, qRT-PCR and Elisa were used to explore wound rehabilitation and anti-fibrosis mechanisms.An in vivo assay revealed that JWSMYA promoted the repairment of acute radiation-induced cutaneous wounds, facilitated MAPK/ERK phosphorylation, inhibited PI3K/AKT activation, reduced the level of alpha-smooth muscle actin (a-sma), collagen type-I alpha 2 (Col1a2) and transforming growth factor-beta 1 (TGF-β1) in cutaneous tissues. However, no statistical difference was found in vascular endothelial growth factor (VEGF).JWSMYA accelerated the repair of acute radiation-induced cutaneous wounds, which might be associated with the MAPK/ERK pathway. In addition, PI3K/AKT might be associated with the inhibition of fibrosis and the promotion of high-quality wound healing.