Severe
acute pancreatitis remains a life-threatening disease with a high mortality rate among a defined proportion of those affected. Apoptosis has been hypothesized to be a beneficial form of cell death in
acute pancreatitis.
Honokiol, a low-molecular-weight
natural product, possesses the ability of anti-
inflammation and apoptosis induction. Here, we investigate whether
honokiol can ameliorate severe
acute pancreatitis and the associated
acute lung injury in a mouse model. Mice received six
injections of
cerulein at 1-h intervals, then given one
intraperitoneal injection of bacterial
lipopolysaccharide for the induction of severe
acute pancreatitis. Moreover, mice were intraperitoneally given vehicle or
honokiol 10 min after the first
cerulein injection.
Honokiol protected against the severity of
acute pancreatitis in terms of increased serum
amylase and
lipase levels, pancreas pathological injury, and associated
acute lung injury.
Honokiol significantly reduced the increases in serum
tumor necrosis factor-α,
interleukin 1, and
nitric oxide levels 3 h and serum high-mobility group box 1 24 h after
acute pancreatitis induction.
Honokiol also significantly decreased
myeloperoxidase activities in the pancreas and the lungs. Endoplasmic reticulum stress-related molecules eIF2α (phosphorylated) and CHOP
protein expressions, apoptosis, and
caspase-3 activity were increased in the pancreas of mice with severe
acute pancreatitis, which was unexpectedly enhanced by
honokiol treatment. These results suggest that
honokiol protects against
acute pancreatitis and limits the spread of inflammatory damage to the lung in a severe
acute pancreatitis mouse model. The acceleration of pancreatic cell apoptosis by
honokiol may play a pivotal role.