20-Hydroxy-3-oxolupan-28-oic
acid (
HOA), a
lupane-type
triterpene, was obtained from the leaves of Mahonia bealei, which is described in the Chinese Pharmacopeia as a remedy for
inflammation and related diseases. The anti-inflammatory mechanisms of
HOA, however, have not yet been fully elucidated. Therefore, the objective of this study was to characterize the molecular mechanisms of
HOA in
lipopolysaccharide (LPS)-stimulated RAW264.7 cells.
HOA suppressed the release of
nitric oxide (NO), pro-inflammatory
cytokine tumor necrosis factor α (TNF-α), and
interleukin 6 (IL-6) in LPS-stimulated RAW264.7 macrophages without affecting cell viability. Quantitative real-time reverse-transcription polymerase chain reaction (RT-qPCR) analysis indicated that
HOA also suppressed the gene expression of inducible
NO synthase (iNOS), TNF-α, and
IL-6. Further analyses demonstrated that
HOA inhibited the phosphorylation of upstream signaling molecules, including p85, PDK1, Akt, IκBα, ERK, and JNK, as well as the nuclear translocation of nuclear factor κB (NF-κB) p65. Interestingly,
HOA had no effect on the LPS-induced nuclear translocation of
activator protein 1 (AP-1). Taken together, these results suggest that
HOA inhibits the production of
cytokine by downregulating iNOS, TNF-α, and
IL-6 gene expression via the downregulation of
phosphatidylinositol 3-kinase (PI3K)/Akt and
mitogen-activated protein kinases (MAPKs), and the inhibition of NF-κB activation. Our findings indicate that
HOA could potentially be used as an
anti-inflammatory agent for medical use.