Effects of an ethanol extract and the diterpene, xylopic acid, of Xylopia aethiopica fruits in murine models of musculoskeletal pain

Pharm Biol. 2016 Dec;54(12):2978-2986. doi: 10.1080/13880209.2016.1199040. Epub 2016 Jul 18.

Abstract

Context: Fruits of Xylopia aethiopica (Dunal) A. Rich. (Annonaceae) are used traditionally to manage arthritis, headache and other pain disorders.

Objective: The analgesic properties of the X. aethiopica ethanol fruit extract (XAE) and xylopic acid (XA) were evaluated in musculoskeletal pain models.

Materials and methods: Acute muscle pain was induced in gastrocnemius muscle of Sprague-Dawley rats with 3% carrageenan (i.m.). Rats received XAE (30-300 mg/kg), XA (10-100 mg/kg) or morphine (1-10 mg/kg) after 12 h. Effects of XAE and XA on muscle pain were assessed by measuring post-treatment grip strength of the rats. Chronic muscle pain was similarly induced, but drug treatment was on the eighth day and effects of XAE and XA assessed with Randall-Selitto test for hyperlagesia. Acute-skeletal pain was induced in knee joints of rats with 3% carrageenan-kaolin mixture and effects determined 12-h later. Similar induction protocol was used for chronic knee pain with treatment and measurement as done for chronic muscle pain.

Results: XAE and XA significantly and dose-dependently ameliorated both acute muscle (ED50 mg/kg: XAE = 22.9; XA = 6.2) and skeletal hyperalgesia (XAE = 39.9; XA = 17.7) induced by 3% carrageenan. Similarly, chronic skeletal hyperalgesia was reduced by XAE and XA treatment similar to morphine (ED50: XAE = 13.0; XA = 4.6). This reduction was also seen in chronic muscle hyperalgesia (ED50: XAE = 79.1; XA = 42.7). XAE and XA significantly reduced the spread of hyperalgesia to contralateral limbs in both models of chronic hyperalgesia.

Conclusion: These findings establish analgesic properties of the ethanol fruit extract of X. aethiopica and xylopic acid in musculoskeletal pain.

Keywords: Acute pain; carrageenan; chronic pain; kaolin; morphine; myalgia.

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Diterpenes / isolation & purification
  • Diterpenes / therapeutic use*
  • Dose-Response Relationship, Drug
  • Ethanol / therapeutic use
  • Female
  • Fruit*
  • Male
  • Musculoskeletal Pain / drug therapy*
  • Musculoskeletal Pain / metabolism
  • Plant Extracts / isolation & purification
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Treatment Outcome
  • Xylopia*

Substances

  • Diterpenes
  • Plant Extracts
  • Ethanol