Hesperidin induces antinociceptive effect in mice and its aglicone, hesperetin, binds to μ-opioid receptor and inhibits GIRK1/2 currents

► Hesperidin showed depressant and antinociceptive effects only by the i.p. route. ► Hesperidin actions in vivo are mediated by an opioid mechanism of action. ► Hesperetin did not show any central nervous system effects in vivo in mice. ► Hesperetin binds to mu-opioid receptor with low-affinity. ► Hesperetin inhibited inward GIRK1/2 currents expressed in Xenopus oocytes.