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

The inhibitory effect of 15-methoxypinusolidic acid (15-MPA) isolated from Biota orientalis (Cupressaceae) on lipopolysaccharide (LPS)-induced inflammation in microglial BV2 cells was investigated. 15-MPA significantly reduced the expression of inducible nitric oxide synthase (iNOS), the activity of iNOS, 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, interleukin (IL)-6, and cyclooxygenase (COX)-2. However, 15-MPA did not affect LPS-induced degradation of inhibitor kappaB-alpha (IkappaB-alpha) and translocation of nuclear factor-kappaB (NF-kappaB) into the nucleus. LPS-activated p38 MAPK, extracellular signal-regulated 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 iNOS expression and NO production, independent on MAPK and NF-kappaB, suggesting a potential anti-inflammatory effect of the compound on microglial cells.