Anti-hyperalgesic properties of ethanolic crude extract from the peels of Citrus reticulata (Rutaceae).

Thiago C Martins,Ana Caroline Heymanns,Bruna L Turnes,Rachel F Magnago,Daniel F Martins,Karen S.C Wilson,Anna P Piovezan,Jasper Zanco,Luiz A Kanis,Adriele C.A Schneider,Kauê M Custódio,Ana P Batisti,Maria E.M Lisboa

doi:10.1590/0001-3765202020180793

Abstract

The therapeutic effects from Citrus reticulata on painful inflammatory ailments are associated to its flavonoids constituent and phytochemical studies with Citrus genus affirm that the peels have important amounts of it. These bioactive compounds have been a considerable therapeutic source and evaluate potential application of the peel extract is significant. This research aims to investigate the influence of ethanolic crude extract from the peels of Citrus reticulata and its possible mechanism of action in different animal models of pain. The extract reduced hyperalgesia in the second phase of formalin test (vehicle: 501.5 ± 40.0 s; C. reticulata extract 300 mg/kg: 161.8 ± 41.1 s), in the carrageenan model (vehicle at 4th h: 82.5 ± 9.6 %; C. reticulata extract 300 mg/kg at 4th h: 47.5 ± 6.5 %) and in Complete Freund's Adjuvant model (vehicle: 501.5 ± 40.0 s; C. reticulata extract 300 mg/kg: 161.8 ± 41.1 s). The possible contribution of opioidergic and adenosinergic systems in the anti-hyperalgesic effect of C. reticulata extract was observed after treatment, with non-selective antagonists for both systems, which produced reversal effects. In conclusion, these properties of C. reticulata extract suggest a potential therapeutic benefit in treating painful conditions.

Highlights

For many populations, relations based on herbal medicines is being groundwork for treating many inflammatory and painful disorders, given that conventional medicines are associated with many adverse effects, toxicity and drug interactions (Chan et al 2017)
Taking the above discussed into account, the aim of this study was to investigate antinociceptive and anti-hyperalgesic properties of ethanolic crude extract from peels of Citrus reticulata (ECECR) in different animal models of neurogenic and inflammatory pain (Santos et al 1998) and preliminarily explore possible contribution of adenosinergic and opioidergic systems for this effect
Concerning to the anti-hyperalgesic effect of ethanolic crude extract of Citrus reticulata (ECE-CR) in the carrageenan model, different results were obtained depending on the type of treatment, whether it was prophylactic or therapeutic

Summary

Introduction

Relations based on herbal medicines is being groundwork for treating many inflammatory and painful disorders, given that conventional medicines are associated with many adverse effects, toxicity and drug interactions (Chan et al 2017). Development of safe alternatives for treating such diseases from compounds derived from plants have been studied for medicinal purposes and some of them have shown anti-inflammatory and analgesic properties, including Achillea millefolium L., Arnica montana L., Curcuma longa. L. amonh others from Citrus species (Al-Snafi 2016). These properties are associated with naturally occurring bioactive compounds that have been a considerable therapeutic source. Flavonones are the preponderance flavonoids in Citrus species (Waheed et al 2009) and around the world, citrus plants like tangerines are widely consumed by the population, mainly as food supplements. Spain and Brazil account for 60.3% of world tangerine production, while Brazil was the second world leading citrus producer in 2014 (19 million tons) after China (33 million tons) (FAO 2016)

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