Pinian powder in promoting proliferation of keratinocytes and fibroblasts through modulation of Wnt4/β-catenin signaling pathway and accelerating wound healing in mice with chronic skin ulcer

<x>Abstract</x> <sec> <title>Objective:</title> Long-term effects of chronic skin ulcers (CSU) include diminished physical and emotional well-being, an increased risk of cancer in more severe cases, and significant social costs due to inadequate treatment. Pinian powder is a topical Chinese medicine created by the late renowned traditional Chinese medicine (TCM) master WEN Zhuozhi, with a long history of clinical use, and has been proven effective in treating various CSU. However, its exact mechanism of action is unknown. This study aims to investigate the effects and mechanisms of Pinian powder on chronic skin ulcers. </sec> <sec> <title>Methods:</title> A mouse model with skin defects and foreign body implantation was developed. Mice were divided into five groups: Control group, model control group, Pinian powder (PNP) group, inhibitor (MSAB) group, and PNP with inhibitor group. Treatments included saline washes, daily PNP application, intraperitoneal MSAB injection, and combined treatment. Wound healing was assessed on day 1, day 3, day 7, and day 14 using photography and software. Histological and Western blotting assays evaluated epidermal repair and protein expression related to wound healing. Immunofluorescence staining detected specific protein localization and expression. Statistical analysis was conducted using GraphPad Prism software, with significance set at <italic>P</italic>&lt;0.05. </sec> <sec> <title>Results:</title> Clinical cases have demonstrated that Pinian powder can influence epidermal migration, reduce wound secretion, and stimulate granulation tissue formation in chronic skin ulcers. <italic>In vivo</italic> experiments, Pinian powder is applied externally to total skin defects and added to foreign body implantation in a mouse model of CSU. It activates the Wnt4/β-catenin signaling pathway, increases the expression of crucial proteins of fibroblast proliferation and keratinocyte proliferation, such as α-smooth muscle actin (α-SMA), Ki-67, K10, and K14, promotes wound healing. After the action of β-catenin inhibitor MSAB, the effect of Pinian powder was reversed. </sec> <sec> <title>Conclusions:</title> Pinian powder can promote the proliferation of keratinocytes and fibroblasts by activating the Wnt4/β-catenin signaling pathway and accelerating the wound healing of CSU. </sec>