Polyphenolic Hispolon Derived from Medicinal Mushrooms of the Inonotus and Phellinus Genera Promotes Wound Healing in Hyperglycemia-Induced Impairments

Background: This study investigated the wound-healing potential of hispolon, a polyphenolic pigment derived from medicinal mushrooms, under diabetic conditions using both in vitro and in vivo models. Methods: In the in vitro assays, L929 fibroblast cells exposed to high glucose (33 mmol/L) were treated with hispolon at concentrations of 2.5, 5, 7.5, or 10 μmol/L. In the in vivo assays, streptozotocin-induced diabetic rats with excision wounds received daily topical applications of 0.2 g of 5% (w/w) hispolon ointment. Results: Hispolon improved cell viability; suppressed oxidative stress by reducing Reactive Oxygen Species, lipid peroxidation, and oxidative DNA damage; and restored the reduced glutathione/oxidized glutathione ratio. The scratch assay demonstrated that hispolon at 10 μmol/L enhanced fibroblast migration impaired by high-glucose conditions. Treatment with 5% (w/w) hispolon ointment accelerated wound contraction, reduced the epithelialization time, and enhanced tissue regeneration with an efficacy comparable to that of Fespixon^® cream, as shown by histological findings of increased fibroblast activity, collagen deposition, and capillary growth. Hispolon ointment also modulated macrophage polarization in diabetic wounds by reducing M1 markers and enhancing M2 markers. In a diabetic rat dead-space-wound model, 5% (w/w) hispolon ointment reduced the levels of pro-inflammatory cytokines, increased those of anti-inflammatory Cytokines and Growth Factors, and stimulated Type I and III collagen synthesis, effectively promoting wound healing. In incisional wounds, hispolon ointment improved the wound-breaking strength, showing results comparable to that of Fespixon^® cream. Safety assessments confirmed that hispolon ointment showed no acute dermal toxicity. These findings underscore hispolon's potential as a promising candidate for diabetic wound management by mitigating oxidative stress, enhancing tissue regeneration, and accelerating wound healing.

collagen synthesis; high glucose; hispolon; macrophage polarization; wound healing.