Related Mechanism of Limonene Improves LPS-Induced Neuroinflammation

Limonene, a component of volatile oils extracted from citrus plants, is known traditionally to treat inflammation. However, the anti-neuroinflammation efficacy and mechanism remain unclear. In this study, lipopolysaccharide was used as a neuroinflammatory inducer to investigate the mechanism of limonene in combating neuroinflammation in mice. Gas chromatography-mass spectrometry (GCMS) was used to identify the main components of Citrus sinensis (L.) Osbeck essential oil. A total of 21 compounds were identified in Citrus sinensis (L.) Osbeck essential oil, of which limonene, myrcene, and carene were the main components. Limonene was found to reduce LPS-induced neuroinflammatory responses in mice, as evidenced by decreased glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule 1 (IBA-1) levels, along with suppressed expression of inflammatory cytokines. In addition, limonene improved the spatial memory and learning ability of mice caused by neuroinflammation, as well as neuronal death in the cerebral cortex and hippocampus. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results showed that limonene had no obvious toxicity to BV2 cells when the concentration was 4 mg/ml. Transcriptomic analysis revealed the effects of limonene on inflammatory response, immune regulation, and other signaling pathways. These results reveal that limonene may improve LPS-induced neuroinflammation by regulating microglia and astrocyte activation and inflammatory response and may be used as a drug for the treatment of neuroinflammation in the future.