Targeting Oxidative Stress and Apoptosis via PI3K/Akt/Nrf2 Pathway: The Therapeutic Role of Bletilla striata Polysaccharide in Diabetic Wound Repair

Background: Diabetic wounds are challenging and lack efficient therapeutic solutions. Bletilla striata polysaccharide (BSP) has garnered interest for its bioactivity and antioxidant ability in wound healing. This research explores the mechanisms through which BSP alleviates oxidative stress (OS) in L929 cells and prevents cell Apoptosis under high-glucose (HG) conditions. Furthermore, the research evaluates its promise as a novel therapeutic approach for facilitating recovery in diabetic wounds.

Methods: Various doses of glucose and BSP were administered to L929 cells to evaluate their effects on cell viability, OS, activation of the PI3K/Akt/Nrf2 signaling pathway, and Apoptosis. These effects were assessed using CCK-8 assays, commercial kits, and western blots (WBs). For in vivo validation in diabetic mice with skin wounds, Masson's trichrome staining, hematoxylin and eosin (H&E) staining, and WB were employed. Additionally, inhibitors of the PI3K/Akt/Nrf2 signaling pathway were used in both in vitro and in vivo experiments.

Results: In vitro, L929 cells exposed to HG stimuli exhibited OS and Apoptosis. However, BSP mitigated these effects by promoting Nrf2 nuclear translocation through the phosphorylation of PI3K and Akt. In diabetic mice, BSP treatment enhanced wound healing rates compared to the control in vivo. This improvement was clear from a substantial reduction in wound areas, decreased inflammation, robust Collagen deposition, and extensive reepithelization, which resulted from the inhibition of the intrinsic Apoptosis process mediated through the activation of the PI3K/Akt/Nrf2 signaling pathway.

Conclusion: Our research emphasizes that BSP serves as a potential therapeutic resolution targeting diabetic wounds for its excellent OS-relieving and antiapoptosis properties. Our findings reveal the value of natural Polysaccharides in the treatment of the complications of diabetes and indicate that BSP promotes the healing of diabetic wounds via the PI3K/Akt/Nrf2 signaling pathway.

Bletilla striata polysaccharide; antiapoptosis; antioxidant; diabetic wound; high glucose.