Maslinic acid, a natural triterpene from Olea europaea, shows antiallodynic and antinociceptive properties

FR Nieto1, EJ Cobos1, JM Entrena2, A García-Granados3, A Parra3, A Martínez3, JM Baeyens0. 1University of Granada, Department of Pharmacology, Biomedical Research Center and Institute of Neurosciences, 18012, Spain, 2University of Granada, Animal Behavior Assessment Unit. Scientific Instrumentation Center, 18100, Spain, 3University of Granada, Department of Organic Chemistry, 18012, Spain

Antecedents

Maslinic acid (2-alfa, 3-betadihidroxi-28-carboxiolean-12-eno) is a triterpenoid compound found in high amounts in the fruit and leaf of the olive tree (Olea europaea). It is known that maslinic acid inhibits pro-inflammatory cytokines (such as interleukin-6 and tumour necrosis factor alpha) production. Since these cytokines are involved in pain generation and sensitization of pain transmission pathway neurons, we hypothesized that maslinic acid could have antiallodynic and/or analgesic effects.

Methods

Maslinic acid sodium salt (64-512 mg/kg) or its solvent (2% tween 80 in water) was subcutaneously (s.c.) administered to female CD-1 mice (25-30 g) and was tested in several behavioral tests (n=8-12 per group). Acute thermal nociception was measured as the latency to hind paw licking in a hot plate at 50 ºC. Chemically-induced tonic nociception was assessed by the writhing test and the formalin test. Writhings were induced by intraperitoneal injection of 0.6% acetic acid in saline (10 ml/kg), and the number of abdominal constrictions was evaluated. The time spent licking or biting the paw after the intraplantar administration of formalin (5% in saline) was evaluated during 45 minutes. We also evaluated the effects of the topical administration of maslinic acid (1% in triethanolamine salt hydrogel) to the hind paw after formalin injection. Mechanical allodynia was induced by an intraplantar injection of capsaicin (1 μg in 1% DMSO in saline) and the latency to paw withdrawal was evaluated with an electronic von Frey apparatus (force 0.5 g). Motor coordination was assessed by the rotarod test, using increasing speeds of rotation from 4 to 40 r.p.m. over 5 min. Results were compared to vehicle controls by a one-way or two-way ANOVA followed by Bonferroni post hoc test.

The experimental protocol was approved by the University of Granada Research Ethics Commitee.

Results

Table 1. Effects of maslinic acid (s.c.) in several tests for nociception:

*p<0.05; **p<0.01; ***p<0.001.

n.d.: not determined

# only the second (inflammatory) phase but not the first (acute nociceptive) phase of the formalin test was affected.

Interestingly, the topical administration of maslinic acid produced a strongly significant (p<0.01) ipsilateral antonociceptive effect in the formalin test (47.17 ± 6.26%), without affecting the response to formalin in the contralateral paw. The above mentioned effects can not be explained by sedation or motor incoordination since maslinic acid (512 mg/kg, s.c.) had no effect on the rotarod test.

Conclusion

These results demonstrated that the natural compound maslinic acid has analgesic and antiallodynic effects against a broad panel of behavioral tests representative of different types of pain and that at least a part of its effects are mediated peripherally.

Supported by Junta-Andalucía (CTS-109 and FQM-139 groups) and MEC grants.