Pharmacological interaction of α-bisabolol and diclofenac on nociception, inflammation, and gastric integrity in rats

Drug Dev Res. 2018 Feb;79(1):29-37. doi: 10.1002/ddr.21418. Epub 2017 Dec 15.


Preclinical Research & Development The combination of nonsteroidal anti-inflammatory drugs (NSAIDs) with herbal products having analgesic and anti-inflammatory effects may increase their beneficial effects and limit their side effects. In this study, the effects of an interaction between α-bisabolol and the NSAID, diclofenac on nociception (formalin test), inflammation (paw inflammation produced by carrageenan) and gastric injury in rat was assessed. Diclofenac, α-bisabolol, or diclofenac-α-bisabolol combinations produced antinociceptive and anti-inflammatory effects in rat (p < .05). The systemic administration of diclofenac, but not α-bisabolol, produced gastric damage while the diclofenac-α-bisabolol combinations produced limited gastric damage. Effective dose (ED40 ) values were determined for each individual drug and analyzed isobolographically. The theoretical ED40 values for the antinociceptive (98.89 mg/kg) and the anti-inflammatory (41.2 mg/kg) effects differed from the experimental ED40 values (antinociception: 38.7 mg/kg and anti-inflammation: 13.4 mg/kg). We concluded that the interactions between diclofenac and α-bisabolol are synergistic. These data suggest that the diclofenac-α-bisabolol combinations can interact to produce minor gastric damage, thereby offering a safer therapeutic alternative for the clinical management of inflammation and/or inflammatory pain.

Keywords: diclofenac; gastric damage; inflammation; nociception; α-bisabolol.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Carrageenan
  • Diclofenac / therapeutic use*
  • Drug Synergism
  • Edema / chemically induced
  • Edema / drug therapy*
  • Formaldehyde
  • Male
  • Monocyclic Sesquiterpenes
  • Nociception / drug effects*
  • Rats, Wistar
  • Sesquiterpenes / therapeutic use*
  • Stomach / drug effects
  • Stomach / pathology


  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Monocyclic Sesquiterpenes
  • Sesquiterpenes
  • Diclofenac
  • Formaldehyde
  • bisabolol
  • Carrageenan