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Metaxalone Suppresses Production of Inflammatory Cytokines Associated with Painful Conditions in Mouse Macrophages RAW264.7 Cells in Vitro: Synergistic Effect with β-caryophyllene

Yamaguchi M, Levy RM

Current molecular medicine, 2020

Abstract

UNLABELLED: Backgrounds and Objective: Inflammation is implicated in the pathogenesis of many diseases. Inflammatory cytokines with painful conditions are well known as biomarkers in human muscle pain, and they are produced by macrophages. Metaxalone is used as a skeletal muscle relaxant, but the mechanism by which metaxalone acts is unknown. This study was undertaken to investigate whether or not metaxalone exhibits an inhibitory effect on the activity of inflammatory macrophages in vitro.

METHODS: Mouse macrophage RAW264.7 cells were cultured in Dulbecco's Modification of Eagle's Medium containing 10% fetal bovine serum in the presence of metaxalone. Cell growth was assayed by counting the number of cells attached to culture dishes. Inflammatory cytokines released into the culture medium were analyzed with the ELISA kit.

RESULTS: Metaxalone (1-100 μM) was found to decrease the number of macrophages by inhibiting the proliferation and stimulating the death of RAW264.7 cells in vitro. The combination of metaxalone (0.1 or 1 μM) and β-caryophyllene (10 or 50 μM), which alone did not have a significant effect on the cell number, caused potential effects on the growth and death of RAW264.7 cells. Mechanistically, molecular levels of mitogenactivated protein kinase were decreased by treatment with metaxalone or β- caryophyllene, and each effect was enhanced by their combination. Furthermore, levels of caspase-3 were increased by metaxalone or β-caryophyllene and enhanced by…

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