Preclinical Characterization of Antinociceptive Effect of Bergamot Essential Oil and of Its Fractions for Rational Translation in Complementary Therapy.

Damiana Scuteri,Chizuko Watanabe,Giacinto Bagetta,Kengo Hamamura,Michele Crudo,Shinobu Sakurada,Paolo Tonin,Laura Rombolà,Tsukasa Sakurada,Hirokazu Mizoguchi,Maria Tiziana Corasaniti

doi:10.3390/pharmaceutics14020312

Abstract

Bergamot essential oil (BEO) is endowed with consistent and reproducible antinociceptive and anti-allodynic properties when administered via an inhalation route. However, the effects of its main constituents and of its decolored (DEC) and deterpenated (DET) fractions, which are enriched in limonene or in linalool and linalyl acetate, respectively, on spontaneous motor activity related to anxiety and on formalin-induced licking/biting biphasic behavior have never been investigated before. Therefore, the present research aims to characterize the role of BEO components on an experimental pain model that is relevant to clinical translation. Under our present experimental conditions, a paper filter disc soaked with different volumes of the phytocomplex and of its fractions that was applied at the edge of the observation chamber allowed the effects on the spontaneous motor activity and on the formalin-induced nocifensive response in ddY-strain mice to be studied. The present research demonstrated the effects of the DEC fraction of BEO on motor activity and on formalin-induced licking/biting behavior for the first time, proving that limonene is implicated in reduced motor activity and that it is important for the analgesic effect.

Highlights

IntroductionThe translational use of essential oils still requires preclinical validation in support of clinical efficacy and safety
The exposure of the mice to bergamot essential oil (BEO) and to its DEC fraction produced a significant re-4 of 10 duction in the locomotor activity with a progressive increase in the inactivity time, which occurred in a volume-dependent manner
After 20 min of treatment, there was a marked reduction in motor activity that was induced by the inhalation of 800 μL of both BEO and the DEC fraction (p < 0.001)

Summary

Introduction

The translational use of essential oils still requires preclinical validation in support of clinical efficacy and safety. This evidence has already been achieved for bergamot essential oil (BEO) [1]. BEO is produced from the cold pressing of the epicarp and the partly cold pressing of the mesocarp of fresh bergamot fruit (Citrus bergamia Risso et Poiteau), and it is composed of a volatile fraction (93–96%) that includes monoterpene and sesquiterpene hydrocarbons, of which one of the most important is limonene. The volatile fraction includes oxygenated derivatives, such as linalool. There is a nonvolatile fraction (4–7%) that is made up of waxes, polymethoxylated flavones, coumarins, and psoralens such

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Results

Conclusion