Betulinic Acid Inhibits Lps-Induced Mmp-9 Expression by Suppressing Nf-Kb Activation in Bv2 Microglial Cells

The objective of the present study was to evaluate anti-inflammatory effects of betulinic acid on lipopolysaccharide (LPS)-stimulated BV2 microglial cells. Pretreatment of betulinic acid significantly attenuated LPSinduced NO production and protein expression of iNOS. Betulinic acid also significantly suppressed LPS-induced release and expression of cytokines such as TNF-

α

and IL-1

β

. Furthermore, betulinic acid significantly suppressed LPSinduced MMP-9 expression, which has been suggested to play an important role in the migration of activated microglia. In order to understand the possible mechanism by which betulinic acid suppresses LPS-induced cytokine production and migration of microglia, the role of NF-kB, a major proinflammatory transcription factor, was examined. Betulinic acid significantly suppressed LPS-induced degradation of IkB, which retains NF-kB in the cytoplasm. Therefore, nuclear translocation of NF-kB upon LPS stimulation was significantly suppressed bybetulinic acid. Taken together, the present study for the first time demonstrates thatbetulinic acid possesses anti-inflammatory activity and inhibition of microglial migration through the suppression of nuclear translocation of NF-kB in BV2 microglial cells.