γ-Mangostin mitigates impaired wound healing and pyroptosis in human gingival fibroblasts induced by advanced glycation end products

Background/purpose: The incidence of diabetes mellitus (DM) has gradually increased in recent years. DM and its complications impose a substantial burden on healthcare systems. Chronic hyperglycemia results in the accumulation of advanced glycation end products (AGEs), which in turn elevate oxidative stress and inflammation, thereby contributing to diabetic complications, including impaired wound healing. γ-Mangostin, a mangostin isolated from the pericarp of mangosteen fruit, has been reported to possess antioxidant and anti-inflammatory properties. Our study aimed to investigate the effects of γ-mangostin on AGEs-induced impairment of wound healing and inflammaging. Materials and methods: Human gingival fibroblasts (HGFs) were isolated from gingival tissues obtained from patients undergoing crown lengthening surgery. HGFs were treated with AGEs for 24 h, followed by treatment with 0.5–2 μg/mL γ-mangostin for another 24 h. Cell proliferation, wound healing capacity, oxidative stress, cell senescence, pyroptosis, and pro-inflammatory cytokine expression were then assessed. Results: Our study found that γ-mangostin at 0.5–2 μg/mL had no effect on HGFs proliferation rate. Furthermore, γ-mangostin restored AGE-induced wound healing impairment and decreased ROS generation. γ-Mangostin reduced AGEs-induced increases in senescence-related β-galactosidase (SA-β-gal) activity and senescence markers p16 and p21. Furthermore, γ-mangostin decreased the expression of pyroptosis-related markers, including as ASC, NLR family pyrin domain-containing 3 (NLRP3), pro-caspase-1, and cleaved gasdermin D (GSDMD). Finally, γ-mangostin inhibited the AGE-induced production of pro-inflammatory cytokines IL-6 and IL-8. Conclusion: Our findings suggest that AGEs impair wound healing and promote oxidative stress, cellular senescence, pyroptosis, and inflammation. γ-Mangostin treatment mitigated these effects, potentially by attenuating inflammation and pyroptosis, thereby improving wound healing.