Oxysophocarpine Ameliorates Carrageenan-induced Inflammatory Pain via Inhibiting Expressions of Prostaglandin E2 and Cytokines in Mice

Planta Med. 2015 Jul;81(10):791-7. doi: 10.1055/s-0035-1546153. Epub 2015 Jul 1.

Abstract

Oxysophocarpine is an alkaloid extracted from Sophora alopecuroides. We investigated the analgesic effect of oxysophocarpine on carrageenan-induced inflammatory pain in mice, in order to explore its possible mechanisms. Mouse ear swelling tests and carrageenan-induced paw edema tests were used to investigate the effects of oxysophocarpine on inflammatory pain in mice. Morphological changes on inflamed paw sections were measured by hematoxylin-eosin staining. The mRNA and protein expression of extracellular signal-regulated kinase, phosphorylation of extracellular signal-regulated kinase 1/2, cyclooxygenase-2, tumor necrosis factor α, interleukin-1 beta, interleukin-6 and prostaglandin E2 were investigated by real-time quantitative polymerase chain reaction, immunohistochemistry, western-blot and enzyme-linked immunosorbent assay. In our results, oxysophocarpine shows a significant anti-inflammatory effect in the mouse ear swelling test. Oxysophocarpine also significantly reduced the paw edema volume and improved mechanical allodynia threshold value on carrageenan-induced inflammatory pain, as well as relieved paw tissues inflammatory damage and reduced the numbers of neutrophils in mice. Oxysophocarpine significantly suppressed over-expression of cyclooxygenase-2, tumor necrosis factor α, interleukin-1 beta, interleukin-6 and prostaglandin E2, and inhibited the over-phosphorylation of extracellular signal-regulated kinase 1/2. Based on these findings we propose that oxysophocarpine attenuates inflammatory pain by suppressing the levels of phosphorylation of extracellular signal-regulated kinase 1/2, cyclooxygenase-2, prostaglandin E2, tumor necrosis factor α, interleukin-1 beta and interleukin-6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Carrageenan / toxicity
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dinoprostone / antagonists & inhibitors
  • Dinoprostone / metabolism*
  • Edema / chemically induced
  • Edema / drug therapy
  • Gene Expression Regulation / drug effects
  • Inflammation / chemically induced
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Interleukin-1beta / metabolism
  • Mice
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Pain / chemically induced
  • Pain / drug therapy*

Substances

  • Alkaloids
  • Anti-Inflammatory Agents, Non-Steroidal
  • Cytokines
  • Interleukin-1beta
  • oxysophocarpine
  • Carrageenan
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • Mapk1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Dinoprostone