Antinociceptive properties of 25-methoxy hispidol A, a triterpinoid isolated from Poncirus trifoliata (Rutaceae) through inhibition of NF-κB signalling in mice

Phytother Res. 2019 Feb;33(2):327-341. doi: 10.1002/ptr.6223. Epub 2018 Nov 19.

Abstract

The 25-methoxy hispidol A (25-MHA) is a triterpenoid, isolated from the immature fruit of Poncirus trifoliata (Rutaceae). The pretreatment with 25-MHA markedly (p < 0.001) attenuated the formalin-induced biphasic responses as well as acetic acid-induced writhing responses. The intraperitoneal administration of 25-MHA significantly attenuated the mechanical hyperalgesia (p < 0.001) and allodynia (p < 0.05). Similarly, 25-MHA also significantly attenuated (p < 0.001) complete Freund's adjuvant (CFA)-induced paw edema in mice. The 25-MHA treatment significantly attenuated the production of nuclear kappa B (NF-κB) (p65 nuclear subunit). The cytokines are the important mediators of inflammation and pain; however, treatment with 25-MHA exhibited significant inhibition (p < 0.001) on the mRNA expression levels of various inflammatory mediators. The 25-MHA administration also significantly enhanced antioxidant enzymes (p < 0.001) and inhibited the oxidative stress markers. The current study indicates that 25-MHA significantly (p < 0.001) inhibited the nitric oxide (NO) in mice plasma. Similarly, the haematoxylin and eosin (H&E) staining shows that 25-MHA administration significantly inhibited the inflammatory process in the mice paw tissue compared with the CFA-treated group. The 25-MHA treatment did not exhibited any toxicity on the liver, kidney, muscles strength, and motor co-ordination in mice. The 25-MHA was coadministered with the various drugs such as tramadol, piroxicam, and gabapentin to observe the synergistic effect.

Keywords: CFA; allodynia; carrageenan; cytokines; hyperalgesia; nociception.

MeSH terms

  • Analgesics / pharmacology
  • Analgesics / therapeutic use*
  • Animals
  • Carrageenan
  • Down-Regulation / drug effects
  • Edema / chemically induced
  • Edema / drug therapy
  • Freund's Adjuvant
  • Hyperalgesia / chemically induced
  • Hyperalgesia / drug therapy*
  • Hyperalgesia / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Male
  • Mice
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Pain / chemically induced
  • Pain / drug therapy*
  • Pain / metabolism
  • Poncirus / chemistry*
  • Rutaceae / chemistry
  • Signal Transduction / drug effects
  • Triterpenes / pharmacology
  • Triterpenes / therapeutic use*

Substances

  • 25-methoxyhispidol A
  • Analgesics
  • NF-kappa B
  • Triterpenes
  • Nitric Oxide
  • Carrageenan
  • Freund's Adjuvant
  • Nitric Oxide Synthase Type II