Mechanistic action of linalyl acetate: Acyclic monoterpene isolated from bitter orange leaf as anti-inflammatory, analgesic, antipyretic agent: Role of TNF-α, IL1β, PGE2, and COX-2

The intervention of inflammation disorders with conventional synthetic drugs has several hazards. Medicinal plants and their byproducts are beneficial in the treatment of inflammations with greater safety. Herein, the essential oils of bitter orange leaf extract (Citrus aurantium) were characterized via GC-MS, whereby, Linalyl acetate was the most major compound was isolated using column chromatography and identified by NMR analysis. The in vivo inflammation inhibition activity against carrageenan-induced models, and central analgesic effect as well as antipyretic potentiality of linalyl acetate were evaluated in rats. The administration of linalyl acetate (100 and 200 mg/kg) exhibited significant fast onset not long-standing anti-inflammatory effect in rat paw edema model in dose-dependent manner, compared to the control and reference drug. This significant inflammation reduction were supported by improving the antioxidant status of the paw via reduction of malondialdehyde (MDA) level and restoration of glutathione (GSH) levels as well as attenuation of proinflammatory cytokines levels (TNF-α), IL-1b, prostaglandin E2 (PGE2), and COX-2 in paw tissues. Although, the oral administration of linalyl acetate (100 and 200 mg/kg) has minimal analgesic it has potent long-lasting antipyretic activity in rats. The higher dose of linalyl acetate (200 mg/kg) displayed fast-onset anti-inflammatory activity better than the reference drug. Furthermore, linalyl acetate (200 mg/kg) has the best antipyretic activity. These findings shed light on promising medicinal uses of linalyl acetate against numerous inflammatory and hyperthermia ailments that could be attributed to its active constituents.