Synergistic anti-inflammatory potential of Cinnamomum verum and Thymus capitatus essential oils: Mechanism of action and molecular docking studies

Abstract

• Cinnamomum verum and Thymus capitatus essential oils exhibit strong antioxidant and anti-inflammatory activities. • The combination of both oils shows a synergistic anti-inflammatory effect with enhanced potency and selectivity. • This combination significantly inhibited NF-κB activation by dowregulating COX-2, iNOS, and TBK1 gene expression. • Molecular docking studies revealed strong binding affinities of cinnamaldehyde and carvacrol to inflammation-related enzymes. • The study provides a comprehensive in-vitro and in-silico investigation of essential oil synergy in inflammation control. Chronic inflammation plays a central role in the onset of degenerative and metabolic diseases, and the adverse side effects associated with conventional therapies highlight the urgent need to develop safer and more effective natural alternatives. This study investigated the anti-inflammatory potential of Cinnamomum (C.) verum and Thymus (T.) capitatus essential oils (EOs), individually and in combination. C. verum exhibited strong radical scavenging activity and potent anti-inflammatory effect in LPS- stimulated RAW 264.7 macrophages. When combined with T. capitatus, the EOs displayed synergistic interaction, resulting in 5.78 and 3.71 − fold enhancement of the anti-inflammatory potency and improvement of the selectivity indices to 4.9 and 2, respectively compared with their individual effects. The combination significantly downregulated COX-2 and iNOS gene expression by 87.42 % and 87.93 %, respectively, and nearly abolished TBK1 expression (99.2 % inhibition). Molecular docking studies confirmed complementary mechanisms of action, showing that carvacrol enhances the activity of cinnamaldehyde by exerting stronger inhibition of COX-2 and iNOS, while cinnamaldehyde additionally targets TBK1. These findings provide scientific evidence supporting the traditional use of C. verum and T. capitatus EOs as natural food additives and highlight their synergistic potential as safe and effective alternatives to synthetic anti-inflammatory agents, with promising application in functional foods and therapeutic formulations.