PURPOSE: Nitric oxide (NO) is a marker of pulmonary inflammation.In asthma, levels of exhaled NO are elevated and the source of the increased NO is inducible nitric oxide synthase (iNOS) within airway epithelial cell.Epimagnolin and fargesin are compounds which are isolated from the ethanol extract of Magnoliae flos. Magnoliae flos is the seed from the Magnolia and used to treat nasal congestion, headache, sinusitis in Korea.This study investigated whether epimagnolin and fargesin inhibit mitogen-activated protein kinases (MAPKs) activation, iNOS expression and decrease NO production in stimulated human respiratory epithelial cells.
METHODS: An immortal Type II alveolar cell line of human origin (A549) was stimulated with cytomix which was composed of IL-1β, TNF-α, IFN-γ with or without epimagnolin or fargesin at various concentration. We evaluated the cytokine-induced activation of NO production, iNOS expression and the activation of signal transduction pathways of inflammation in the A549 cells.
RESULTS: A549 cells stimulated with cytomix showed increases of iNOS mRNA and protein expression and nitrite accumulation in the cell culture media. However, treatment with epimagnolin or fargesin resulted in decreases of iNOS mRNA and protein expression and nitrite accumulation.Cytomix stimulated a rapid increase in the activities of early intracellular signalling molecules such as extracellular signal-regulated kinase (ERK) and C-Jun N-terminal kinase JNK (JNK), while epimagnolin and fargesin inhibited ERK and p-JNK activation.
CONCLUSION: Epimagnolin and fargesin inhibit intracellular signaling, iNOS expression and decrease production of NO in stimulated human respiratory epithelial cells.
CLINICAL IMPLICATIONS: These results from the present study indicate that epimagnolin and fargesin would be a therapeutic medicine for asthma treatment.
DISCLOSURE: Yang Deok Lee, No Financial Disclosure Information; No Product/Research Disclosure Information