At the gates of the 21st century, it is already known the development of most of the diseases affecting the population is closely related to poor dietary habits. In recent years, nutritional science has been transformed by an explosion of evidence, shedding new light on key compounds and pathways for how diet influences health
and well-being. Among these, some of the most exciting advances are occurring in the field of flavonoids, a large group of polyphenolic compounds of natural origin, ubiquitously found in the plant kingdom as secondary metabolites. Beyond their relevance to plants, flavonoids exhibit multiple biological properties, which have played a significant role in the success of many medical treatments of ancient times, allowing their use to persevere up until our days. Throughout more than 20 years of work, our laboratory has described the potential of several flavonoids for the central nervous system, being pioneer in reporting the sedative and antinociceptive effects
of hesperidin (HID). This compound constitutes the main flavonoid in sweet oranges and lemons, besides being also found in many other edible plants, fundamental to any healthy diet. Since HID is metabolized to its aglicone, hesperetin (HET), and it has been described that it may be more rapidly absorbed and may exhibit more activity than HID, the aim of this study was to evaluate the antinociceptive properties of HET. Chemical and thermal nociception were assessed using the test model of acetic acid-induced writhing and the hot-plate test, respectively, in order to appraise both peripherally and centrally mediated effects of HET. In addition, the locomotor activity test was performed to rule out the possibility that the drug would be affecting animals’ locomotion. The results demonstrated that, at a high dose, HET was able to prevent acetic acid-induced nociception in mice; but it did not exhibit any inhibition of the nociceptive behavior during hot-plate test. In addition, no alterations in locomotion were observed. Together, these results allowed us to propose HET as an antinociceptive agent, acting probably through peripheral mechanisms. Further studies would be necessary in order to determine the exact mechanisms involved and its implications in critical conditions in human health, such as neuropathic pain.