Calycosin alleviates cerulein-induced acute pancreatitis by inhibiting the inflammatory response and oxidative stress via the p38 MAPK and NF-κB signal pathways in mice

Biomed Pharmacother. 2018 Sep:105:599-605. doi: 10.1016/j.biopha.2018.05.080. Epub 2018 Jun 8.

Abstract

Acute pancreatitis (AP) is a common acute abdominal disease accompanied by systemic inflammatory response syndrome, and could even be complicated by multiple-organ damage. This study aimed to examine whether calycosin, an isoflavone isolated from Radix astragali with antioxidant and anti-inflammatory activity, could protect against AP induced by cerulein. To this end, Balb/C mice were injected with cerulein (50 μg/kg) to establish the animal model of AP. Calycosin (25 and 50 mg/kg, p.o.) was administered 1 h prior to the first cerulein injection. After the last injection of cerulein, the mice were sacrificed and blood was obtained for cytokine analysis. The pancreas was removed for morphological examination, myeloperoxidase (MPO) and malondialdehyde (MDA) analyses, immunohistochemistry, and western blot analysis. Calycosin treatment reversed the increased serum levels of amylase and lipase, alleviated the pathological damage in the pancreas, and decreased the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β in mice with AP. Additionally, calycosin significantly reduced cerulein-induced pancreatic edema, inhibited MPO activity and increased superoxide dismutase (SOD) activity, and inhibited the expression of NF-κB/p65 and phosphorylation of the inhibitor of NF-κB (IκBα) and p38 MAPK. These results suggested that calycosin protects against AP by exerting anti-inflammatory and anti-oxidative stress effects via the p38 MAPK and NF-κB signal pathways. Calycosin's benefits for AP patients need to be explored further.

Keywords: Acute pancreatitis; Calycosin; Cerulein; Inflammatory response; Radix astragali.

MeSH terms

  • Acute Disease
  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / therapeutic use*
  • Astragalus propinquus
  • Ceruletide
  • Cytokines / immunology
  • Disease Models, Animal
  • Drugs, Chinese Herbal / chemistry
  • Isoflavones / isolation & purification
  • Isoflavones / therapeutic use*
  • Male
  • Mice, Inbred BALB C
  • NF-kappa B / metabolism*
  • Oxidative Stress / drug effects*
  • Pancreatitis / chemically induced
  • Pancreatitis / drug therapy*
  • Pancreatitis / immunology
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Drugs, Chinese Herbal
  • Isoflavones
  • NF-kappa B
  • 7,3'-dihydroxy-4'-methoxyisoflavone
  • Ceruletide
  • Huang Qi
  • p38 Mitogen-Activated Protein Kinases