Anti-Inflammatory, Antihyperalgesic, and Gastric Safety Profiling of Ocimene: Attenuation of Nonsteroidal Anti-Inflammatory Drug-Induced Gastric Ulcers by Modulating Toll-like Receptor 4 and Pyroptosis Pathways.

Monocyclic monoterpenoid ocimene (OC) was evaluated as a potential inhibitor of TLR4/NLRP3/GSDMD-driven pyroptosis, implicated in conditions such as chronic pain, inflammation, and gastric ulcers. This study investigated OC's protective effects against indomethacin (IND)-induced gastric ulcers, aiming to identify an analgesic and anti-inflammatory agent with enhanced gastric safety. OC's analgesic efficacy was demonstrated by reducing formalin-evoked paw licking, writhing provoked by acetic acid-induced and tail immersion reaction latencies in animal models. Anti-inflammatory effects were confirmed through reduced paw edema (formalin and carrageenan), along with in vitro suppression of protein denaturation and membrane stabilization. qRT-PCR showed that OC significantly (p < 0.001) downregulated TLR4, MyD88, NFκB, NLRP3, and inflammatory mediators (IL-18, IL-1β, caspase-1, ASC, GSDMD, COX-1, COX-2) with upregulation of anti-inflammatory cytokines IL-4 and IL-10. ELISA results indicated a reduction in the oxidative stress marker MDA and inflammatory mediators PGE-2 and 5-LOX, with increased antioxidant markers GSH, CAT, and SOD. Macroscopic and histological analysis showed that OC provided gastric protection by reducing the ulcer index (UI) and improving ulcer scores, with effects comparable to omeprazole. In summary, OC shows potential as a safe antinociceptive and anti-inflammatory agent, effectively reducing gastric ulcer risk by mitigating pyroptosis and inflammation, critical for treating chronic inflammatory conditions with hyperalgesia.