Tanshinone IIA potentiates the therapeutic efficacy of glucocorticoids in lipopolysaccharide-treated HEI-OC1 cells through modulation of the FOXP3/Nrf2 signaling pathway

• Tanshinone IIA (TA) enhances the therapeutic efficacy of glucocorticoids (GCs) in an in vitro model of sudden sensorineural hearing loss (SSNHL) by promoting cell proliferation and suppressing apoptosis in lipopolysaccharide-treated HEI-OC1 cells. • TA upregulates HDAC2 expression via NRF2-mediated transcriptional activation, with the NRF2 binding site identified at bases 419–429 (ATGACACTCCA) in the HDAC2 promoter. • TA also upregulates FOXP3, which in turn activates NRF2 transcription through a predicted FOXP3 binding site at bases 864–870 (GCAAACA) in the NRF2 promoter, revealing a FOXP3/Nrf2 signaling cascade. • These findings suggest that TA may serve as a promising adjunct to overcome GC resistance in SSNHL patients, offering a potential therapeutic strategy for this challenging condition.