Anti-inflammatory effects of compounds alpha-humulene and (-)-trans-caryophyllene isolated from the essential oil of Cordia verbenacea

Eur J Pharmacol. 2007 Aug 27;569(3):228-36. doi: 10.1016/j.ejphar.2007.04.059. Epub 2007 May 22.


This study evaluated the anti-inflammatory properties of two sesquiterpenes isolated from Cordia verbenacea's essential oil, alpha-humulene and (-)-trans-caryophyllene. Our results revealed that oral treatment with both compounds displayed marked inhibitory effects in different inflammatory experimental models in mice and rats. alpha-humulene and (-)-trans-caryophyllene were effective in reducing platelet activating factor-, bradykinin- and ovoalbumin-induced mouse paw oedema, while only alpha-humulene was able to diminish the oedema formation caused by histamine injection. Also, both compounds had important inhibitory effects on the mouse and rat carrageenan-induced paw oedema. Systemic treatment with alpha-humulene largely prevented both tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) generation in carrageenan-injected rats, whereas (-)-trans-caryophyllene diminished only TNFalpha release. Furthermore, both compounds reduced the production of prostaglandin E(2) (PGE(2)), as well as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) expression, induced by the intraplantar injection of carrageenan in rats. The anti-inflammatory effects of alpha-humulene and (-)-trans-caryophyllene were comparable to those observed in dexamethasone-treated animals, used as positive control drug. All these findings indicate that alpha-humulene and (-)-trans-caryophyllene, derived from the essential oil of C. verbenacea, might represent important tools for the management and/or treatment of inflammatory diseases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / isolation & purification
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Brazil
  • Cordia / chemistry*
  • Cyclooxygenase 2 / drug effects
  • Cyclooxygenase 2 / metabolism
  • Dexamethasone / pharmacology
  • Dinoprostone / biosynthesis
  • Edema / chemically induced
  • Edema / drug therapy
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / metabolism
  • Male
  • Medicine, Traditional
  • Mice
  • Monocyclic Sesquiterpenes
  • Nitric Oxide Synthase Type II / drug effects
  • Nitric Oxide Synthase Type II / metabolism
  • Oils, Volatile / chemistry
  • Plant Components, Aerial
  • Plants, Medicinal
  • Polycyclic Sesquiterpenes
  • Rats
  • Rats, Wistar
  • Sesquiterpenes / isolation & purification
  • Sesquiterpenes / pharmacology*
  • Tumor Necrosis Factor-alpha / drug effects
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-1beta
  • Monocyclic Sesquiterpenes
  • Oils, Volatile
  • Polycyclic Sesquiterpenes
  • Sesquiterpenes
  • Tumor Necrosis Factor-alpha
  • humulene
  • Dexamethasone
  • caryophyllene
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Dinoprostone