Polysaccharide from Campanumoea javanica Bl. accelerate wound healing via moderating TGF-β1/Smad3 pathways and promoting SIRT1-mediated macrophage polarization in rats

Ethnopharmacological relevance: Abnormal wound healing, including delayed and excessive healing, is a significant clinical challenge requiring multidisciplinary interventions. Campanumoea javanica Bl., traditionally used postoperatively for hemostasis, immune enhancement, and postsurgical repair in minority ethnic regions, has shown potential in promoting wound healing. However, the underlying mechanisms remain unclear.

Aim of the study: This study investigates the therapeutic mechanism of a purified polysaccharide fraction derived from C. javanica (CJPP) on wound healing in rats and cells using histopathological analysis, immunomics, and proteomics.

Materials and methods: Sprague-Dawley (SD) rats were divided into six groups: normal control, model (untreated wound), Chuyuan compound peptide (positive control), and CJPP low-, medium-, and high-dose groups. After creating standardized wounds, treatments were administered daily to the respective groups, while the normal control and model groups received saline. Wound healing was assessed on days 0, 4, 7, and 14. Blood samples were collected for biochemical analysis of cytokines, and wound tissues were harvested for histopathological evaluation and immunomic/proteomic studies. The mechanism of action was further verified through cell experiments.

Results: Biochemical, histopathological, immunomic, and proteomic analyses demonstrated that CJPP significantly accelerated wound healing rates in rats. It increased levels of the anti-inflammatory cytokine IL-10 while reducing pro-inflammatory cytokines. Histologically, CJPP improved the structure of wounded skin by promoting Collagen fiber deposition and microvascular proliferation. Additionally, CJPP facilitated macrophage polarization from the pro-inflammatory M1 macrophage to the reparative M2 macrophage. Mechanistically, CJPP upregulated the expression of the SIRT1 protein and modulated the TGF-β1/SMAD3 signaling pathway, which are critical regulators of wound healing.This conclusion was verified by adding SIRT1 and TGF-β/Smad inhibitors in vitro experiments with RAW264.7 and HFF-1 cells.

Conclusion: The results indicate that CJPP promotes wound healing by facilitating macrophage polarization from M1 to M2 through the SIRT1 protein and modulating the TGF-β1/SMAD3 pathway. This study provides insight into the pharmacological mechanisms underlying the traditional use of C. javanica in wound healing.

Campanumoea javanica polysaccharide; Macrophage polarization; SIRT1; TGF-β1/Smad3 pathway; Wound healing.