Honokiol Attenuates the Severity of Acute Pancreatitis and Associated Lung Injury via Acceleration of Acinar Cell Apoptosis

Abstract

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.

Honokiol protects against renal ischemia/reperfusion injury via the suppression of oxidative stress, iNOS, inflammation and STAT3 in rats

“…In the present study, honokiol administration significantly decreased the levels of caspase-3 in the IRI rats. Weng et al suggested that honokiol attenuates the severity of acute pancreatitis and lung injury through suppression of apoptosis and caspase-3 activity (44). Honokiol also inhibits the activation of caspase-3 and caspase-9 in H 2 O 2 -induced apoptosis in human lens epithelial cells (45).…”

HMGB1 in health and disease

“…In patients and animals with AP, serum levels of HMGB1 are significantly elevated and positively correlate with the severity of this disease (Kocsis et al, 2009; Yasuda et al, 2007; Yasuda et al, 2006). Importantly, inhibiting the release or cytokine activity of HMGB1 (e.g., HMGB1 neutralizing antibody, ethyl pyruvate, danaparoid sodium, cisplatin, A box, antithrombin III, and pyrrolidine dithiocarbamate) confers protection against experimental AP (Cheng et al, 2007; Hagiwara et al, 2009g; Jo et al, 2013; Luan et al, 2013a; Luan et al, 2012; Luan et al, 2013b; Sawa et al, 2006; Weng et al, 2012; Yan et al, 2012a; Yang et al, 2009b; Yang et al, 2008; Yuan et al, 2009; Zhang et al, 2010). However, intracellular HMGB1 in the pancreas protects against acute pancreatitis (Kang et al, 2013b).…”

Rhein Induces a Necrosis‐Apoptosis Switch in Pancreatic Acinar Cells

“…We previously showed that DCQD can ameliorate pancreatic inflammation and pathological damage by inducing a necrosis-apoptosis switch in AR42J cells and a rat model of AP [7]. Other studies similarly reported that treatment with various components of DCQD induces apoptosis and reduces necrosis of acinar cells in AP [8–10]. However, the active components and mechanism underlying this effect remain uncertain.…”