Artesunate alleviates radiation‐induced submandibular gland epithelial cell damage in rats by reducing inflammation and apoptosis

Salivary hypofunction is a common complication in patients with head and neck cancers following radiotherapy (RT). RT-induced inflammation in salivary gland cells leads to apoptosis and fibrosis. Artesunate (ART) is a bioactive compound with anti-inflammatory and anti-fibrosis properties. This study aimed to investigate the protective effects of ART on X-ray-induced injury of submandibular gland (SMG) epithelial cells in rats. Second-generation SMG epithelial cells were randomly divided into five groups: natural control group (NC), irradiated group (IR), and irradiated groups treated with ART at concentrations of 5, 10, and 20 μM. Cells were harvested 48 h postirradiation for analysis. The results demonstrated that ART attenuated the damage to AQP5, a crucial indicator of salivary gland function, as evidenced by the decreased expression of AQP5 at both mRNA and protein levels. Additionally, ART decreased the expression of inflammatory cytokines: IL-6 and TNF-α. TUNEL staining revealed reduced apoptosis in the ART groups, particularly the IR + 10 μM group. RT-PCR and Western blot analysis of apoptosis cytokines Bax/Bcl-2 and Caspase-3 confirmed these findings. Furthermore, ART inhibited the expression of NF-κB at both mRNA and protein levels. In conclusion, these results suggest that ART may reduce inflammation and apoptosis in SMG epithelial cells following radiation by inhibiting the NF-κB pathway.