Carnosol exerts anti-inflammatory effects in pulpitis by inhibiting the RAGE/NF-κB signalling pathway

Effective pulpal inflammation control remains a global challenge. This study evaluated the protective efficacy of carnosol (CA) and its underlying mechanism both in vivo and in vitro. Human dental pulp cells (hDPCs) were isolated from third molars or orthodontically healthy teeth and treated for 6 h with 1 µg/mL lipopolysaccharide (LPS) alone or in combination with CA. Levels of receptor for advanced glycation end products (RAGE), interleukin (IL)-1β, IL-6, and tumour necrosis factor -α, and nuclear factor kappa B (NF-κB) activity, were examined. Sprague-Dawley rats were divided into: drilled (pulp exposure), CA-treated, DMSO-treated, and intact controls CA treatment at 2.5, 5, and 10 µM markedly suppressed pro-inflammatory cytokine expression in LPS-treated hDPCs in a concentration-dependent manner. CA treatment suppressed LPS-induced RAGE expression, reduced NF-κB phosphorylation, and blocked nuclear translocation of the NF-κB p65 subunit in hDPCs. RAGE silencing inhibited the NF-κB signalling pathway, leading to reduced inflammatory cytokine expression, and enhanced anti-inflammatory capacity of CA in vitro. CA treatment modulated RAGE mRNA expression without affecting the stability of the RAGE protein. In rats, CA administration to inflamed dental pulp reduced pulpal inflammation. CA alleviates pulpal inflammation through the RAGE/NF-κB pathway, which indicates its potential as a therapeutic option for managing pulpitis.