Salvianolic acid B decreases oxidative stress and alleviates the tumor-promoting effects of arecoline in oral cancer.

Arecoline, which is a primary alkaloid in areca nuts, contributes in key ways to the development of oral submucous fibrosis and the subsequent oral cancer through the induction of oxidative stress, promotion of fibrosis, and activation of oncogenic signaling. Salvianolic acid B (SAB) is the most abundant water-soluble phenolic compound found in Salvia miltiorrhiza Bunge. SAB appears to have the potential to mitigate the effects of arecoline. However, the interaction between SAB and arecoline in oral cancer has been less frequently discussed. Therefore, we conducted this study in which SCC-4 tongue cancer cells were treated with arecoline alone or in combination with SAB. The effects on collagen contraction, cell migration, reactive oxygen species (ROS) production, and transcriptomic alterations were assessed. Arecoline increased collagen contraction, ROS accumulation, and the activation of tumor-promoting pathways, including TGF-β/Smad, EGFR, MAPK, and ferroptosis. In contrast, SAB effectively decreased collagen contraction, reduced cell migration, and attenuated oxidative stress in a dose-dependent manner. Moreover, in the presence of arecoline, SAB supplementation reversed fibrosis-related processes, modulated metabolic activity, and enhanced DNA repair mechanisms, thereby counteracting arecoline-induced oncogenic effects. Therefore, SAB, through its ability to reduce oxidative stress, fibrosis, and metabolic dysregulation, is a promising therapeutic candidate for mitigating arecoline-induced tumor progression. Our study offers novel insights into the role of SAB in protecting against the pathophysiology of oral cancer and highlights its potential as a natural compound for the prevention and treatment of this disease.