Fucoxanthin improves stomatitis by regulating mitochondrial function and cGAS-STING signaling

Fucoxanthin (FX), a natural carotenoid derived from marine brown algae, possesses extremely high anti-inflammatory activity. However, the precise mechanisms underlying its protective effects against stomatitis remain to be elucidated. This study aimed to explore the protective effects and mechanisms of FX in the treatment of stomatitis. Histopathological examination was conducted on oral mucosal tissues from rats with 5-fluorouracil (5-FU)-induced oral mucositis. Western blotting and immunofluorescence staining were used to explore the epithelial-mesenchymal transition (EMT), tight junction proteins, mitochondrial function, mitochondrial autophagy and the expression of key molecules involved in the cGAS-STING signaling in HOKs. Moreover, molecular docking analysis was applied to predict the binding interactions between FX and cGAS/STING proteins. The results showed that FX markedly alleviated the symptoms of whitening and swelling of the oral mucosa and thinning of the epithelium in 5-FU-induced rats. In LPS-induced HOKs, FX restored the abnormal localization of Occludin and ZO-1 proteins, ameliorated mitochondrial dysfunction, and inhibited EMT. Furthermore, the protein levels of cGAS, STING, and TBK1 were downregulated by FX treatment. Molecular docking revealed direct binding between FX and both cGAS and STING. Collectively, these findings indicate that FX may alleviate LPS-induced stomatitis by ameliorating mitochondrial dysfunction to reduce mitochondrial DNA (mtDNA) release, thereby inhibiting the cGAS-STING signaling pathway. These results suggest that FX holds promise as a therapeutic candidate for stomatitis.