Carvacrol alleviates LPS-induced myocardial dysfunction by inhibiting the TLR4/MyD88/NF-κB and NLRP3 inflammasome in cardiomyocytes

BackgroundSepsis-induced myocardial dysfunction (SIMD) may contribute to the poor prognosis of septic patients. Carvacrol (2-methyl-5-isopropyl phenol), a phenolic monoterpene compound extracted from various aromatic plants and fragrance essential oils, has multiple beneficial effects such as antibacterial, anti-inflammatory, and antioxidant properties. These attributes make it potentially useful for treating many diseases. This study aims to investigate the effects of CAR on LPS-induced myocardial dysfunction and explore the underlying mechanism.ResultsH9c2 cells were stimulated with 10 mu g/ml LPS for 12 h, and c57BL/6 mice were intraperitoneally injected with 10 mg/kg LPS to establish a septic-myocardial injury model. Our results showed that CAR could improve cardiac function, significantly reduce serum levels of inflammatory cytokines (including TNF-alpha, IL-1 beta, and IL-6), decrease oxidative stress, and inhibit cardiomyocyte apoptosis in LPS-injured mice. Additionally, CAR significantly downregulated the expression of TLR4, MyD88, and NF-kappa B in LPS-injured mice and H9c2 cells. It also inhibited the upregulation of inflammasome components (such as NLRP3, GSDMD, and IL-1 beta) in H9c2 cells triggered by LPS.ConclusionTaken together, CAR exhibited potential cardioprotective effects against sepsis, which may be mainly attributed to the TLR4/MyD88/NF-kappa B pathway and the NLRP3 inflammasome.