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
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 their
combination. Notably, productions of inflammatory cytokines, including tumor necrosis
factor-α, interleukin-6 or prostaglandin E2, which were enhanced by lipopolysaccharide
(LPS), were repressed by culturing with metaxalone. Levels of cyclooxygenase (COX)-1,
COX-2 and nuclear factor kappa B, which were increased by LPS treatment, were
reduced by metaxalone.
Conclusion: Metaxalone was found to suppress the activity of inflammatory
macrophages in vitro.