Matrix metalloproteinase (MMP)-9 plays an important role in the pathogenesis of
bronchial asthma.
Neovastat, having significant antitumor and antimetastatic properties, is classified as a naturally occurring multifunctional
antiangiogenic agent. We evaluated the
therapeutic effect of
Neovastat on airway
inflammation in a mouse model of
asthma. BALB/c mice were immunized subcutaneously with
ovalbumin (OVA) on days 0, 7, 14, and 21 and challenged with inhaled OVA on days 26, 29, and 31.
Neovastat was administrated by gavage (5 mg/kg
body weight) three times with 12 h intervals, beginning 30 min before OVA inhalation. On day 32, mice were challenged with inhaled
methacholine, and enhanced pause (Penh) was measured as an index of
airway hyperresponsiveness. The severity of airway
inflammation was determined by differential cell count of bronchoalveolar lavage (BAL) fluid. The MMP-9 concentration in BAL fluid samples was measured by ELISA, and MMP-9 activity was measured by zymography. The untreated
asthma group showed an increased inflammatory cell count in BAL fluid and Penh value compared with the normal control group. Mice treated with
Neovastat had significantly reduced Penh values and inflammatory cell counts in BAL fluid compared with untreated asthmatic mice. Furthermore, mice treated with
Neovastat showed significantly reduced MMP-9 concentrations and activity in BAL fluid. These results demonstrate that
Neovastat might have new therapeutic potential for airway asthmatic
inflammation.