A pinusolide derivative, 15-methoxypnusolidic acid from Biota orientalis inhibits inducible nitric oxide synthase in microglial cells:: Implication for a potential anti-inflammatory effect

The inhibitory effect of 15-methoxypinusotidic acid (15-MPA) isolated from Bioto orientalis (Cupressaceae) on lipopotysaccharide (LPS)-induced inflammation in microglial BV2 cells was investigated. 15-MPA significantly reduced the expression of inducible nitric oxide synthase (MOS), the activity of MOS, and the production of nitric oxide (NO) in LPS-stimulated BV2 cells. In addition, 15-MPA significantly suppressed the expressions of tumor necrosis factor (TNF)-alpha., interteukin (IL)-6, and cyclooxygenase (COX)-2. However, 15-MPA did not affect LPS-induced degradation of inhibitor kappa B-alpha (I kappa B-alpha) and translocation of nuclear factor-kappa B (NF-kappa B) into the nucleus. LPS-activated p38 MAPK, extraceltular signal- regutated kinase (ERK)-1/2,and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) were not affected by 15-MPA. Taken together, this study demonstrates that 15-MPA inhibits LPS-induced MOS expression and NO production, independent on MAPK and NF-kappa B, suggesting a potential anti -inflammatory effect of the compound on microglial cells. (c) 2007 Elsevier B.V. All. rights reserved.