Analgesic and anti-inflammatory activities of Citrus aurantium L. blossoms essential oil (neroli): involvement of the nitric oxide/cyclic-guanosine monophosphate pathway

J Nat Med. 2015 Jul;69(3):324-31. doi: 10.1007/s11418-015-0896-6. Epub 2015 Mar 12.


The analgesic and anti-inflammatory properties of Citrus aurantium L. blossoms essential oil (neroli) were investigated in mice and rats. The analgesic activity of neroli was assessed by acetic acid-induced writhing and Eddy's hot plate methods, while acute and chronic anti-inflammatory effects were investigated by inflammatory paw edema in rat and the cotton pellet-induced granuloma tissue model, respectively. Mechanistic studies were conducted using L-nitro arginine methyl ester (L-NAME), an inhibitor of NO synthase. Neroli significantly decreased the number of acetic acid-induced writhes in mice compared to animals that received vehicle only. Also, it exhibited a central analgesic effect, as evidenced by a significant increase in reaction time in the hot plate method. The oil also significantly reduced carrageenan-induced paw edema in rats. The inhibitory activity of neroli (especially at 40 mg/kg) was found to be very close to the standard drug, diclofenac sodium (50 mg/kg). In cotton pellet-induced granuloma, neroli was effective regarding the transudate and granuloma formation amount. Neroli was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS) and twenty-three constituents, representing 91.0 % of the oil, were identified. The major components of neroli were characterized as linalool (28.5 %), linalyl acetate (19.6 %), nerolidol (9.1 %), E,E-farnesol (9.1 %), α-terpineol (4.9 %), and limonene (4.6 %), which might be responsible for these observed activities. The results suggest that neroli possesses biologically active constituent(s) that have significant activity against acute and especially chronic inflammation, and have central and peripheral antinociceptive effects which support the ethnomedicinal claims of the use of the plant in the management of pain and inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Citrus / chemistry*
  • Cyclic GMP / metabolism
  • Drug Evaluation, Preclinical
  • Edema / chemically induced
  • Edema / drug therapy
  • Flowers / chemistry*
  • Gas Chromatography-Mass Spectrometry
  • Male
  • Mice
  • Nitric Oxide / metabolism
  • Oils, Volatile / pharmacology*
  • Plant Extracts / pharmacology*
  • Plant Oils / pharmacology
  • Rats, Wistar
  • Second Messenger Systems


  • Analgesics
  • Anti-Inflammatory Agents
  • Oils, Volatile
  • Plant Extracts
  • Plant Oils
  • Nitric Oxide
  • Cyclic GMP