In the present study, the effect of
asiatic acid, a natural
triterpenoid compound, on murine experimental
colitis induced by
dextran sulfate sodium (DSS) and its possible mechanism were examined in vivo and vitro.
Oral administration of
asiatic acid dose-dependently attenuated the loss of
body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic scores of musco and
myeloperoxidase activity were also significantly reduced by
asiatic acid treatment.
Protein and
mRNA levels of DSS-induced pro-inflammatory
cytokines in colon, including TNF-α, IL-1β,
IL-6 and IFN-γ, were markedly suppressed by
asiatic acid. At the same time, decreased activation of caspase-1 in peritoneal macrophages was detected in
asiatic acid-treated mice, which suggested that the NLRP3
inflammasome activation was suppressed. In addition, we also found that
asiatic acid dose-dependently inhibited IL-1β secretion, caspase-1 activation as well as
inflammasome assembling in vitro. Furthermore, the mechanism of
asiatic acid was related to the inhibition of mitochondrial
reactive oxygen species generation and prevention of mitochondrial membrane potential collapse. Taken together, our results demonstrate the ability of
asiatic acid to inhibit NLRP3
inflammasome activation and its potential usage in the treatment of
inflammatory bowel diseases.