Tenuigenin down-regulates the release of nitric oxide, matrix metalloproteinase-9 and cytokines from lipopolysaccharide-stimulated microglia

Tenuigenin (TEN), an active component of Polygala tenuifolia root extracts, has been shown to provide neuroprotection in neurodegenerative disorders. To date, most of these studies have focused on the effect that TEN has on neurons. Because activated microglia can release neurotoxic factors that cause neuronal damage, the present study was designed to investigate the effects of TEN on activated microglia. The results showed that TEN can significantly decrease the release of nitric oxide (NO) from lipopolysaccharide (LPS)-activated rat microglia in a dose-dependent manner. The western blotting results showed that TEN did not inhibit iNOS expression at protein level. However, the electron paramagnetic resonance (EPR) technique revealed that TEN directly scavenged the NO radical. Additionally, TEN can significantly decrease the secretion and mRNA levels of matrix metalloproteinase-9 (MMP-9) and pro-inflammatory cytokines (TNF-α/IL-1β) in activated microglia. At a high dose (10−4M), TEN can significantly inhibit the secretion of another gelatinolytic MMP, MMP-2, but it had no effect on the mRNA level of MMP-2. In conclusion, these results suggest that TEN exerts an anti-inflammatory effect by down-regulating the release of NO, MMP-9 and cytokines.