hyperoside and Pain

The antinociceptive profile of St. John's Wort (SJW) was investigated in mice in a condition of acute thermal and chemical pain, together with the mechanism that might underlie this effect. A dried extract of SJW induced a prolonged antinociception that persisted for 120 minutes after administration. The thermal antinociception was prevented by naloxone and by the protein kinase C (PKC) activator PMA, whereas the chemical antinociception was prevented by PMA, remaining naloxone insensitive. A chloroform (CHL) and a methanol (MET) fraction, obtained to investigate the involvement of the SJW main components, hyperforin and hypericin/flavonoid, respectively, increased pain threshold with a time course comparable to the dried extract. The CHL antinociception was prevented by naloxone, whereas the MET antinociception was antagonized by PMA. Purified hyperforin and hypericin showed an antinociceptive efficacy comparable to CHL and MET, respectively. Conversely, flavonoids were devoid of any effect. The administration of yohimbine and atropine did not modify SJW, CHL and MET antinociception. These results indicate that both CHL and MET fractions mediate the SJW-induced antinociception. In particular, the presence of hypericin was fundamental to induce both thermal and chemical antinociception through the inhibition of the PKC activity, whereas hyperforin selectively produced a thermal opioid antinociception.. This article presents evidence of a persistent thermal and chemical antinociception of SJW that is mainly mediated by PKC-inhibiting mechanisms. These findings identify important targets for a longer-acting activation of endogenous pain systems and should potentially help clinicians who seek safe, tolerable, and prolonged treatments for pain relief.

Topics: Acetic Acid; Analgesics; Analgesics, Opioid; Animals; Anthracenes; Chromatography, High Pressure Liquid; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Administration Routes; Drug Administration Schedule; Drug Compounding; Hypericum; Male; Mice; Naloxone; Naltrexone; Narcotic Antagonists; Pain; Pain Measurement; Pain Threshold; Perylene; Phorbol Esters; Phytotherapy; Protein Kinase C; Quercetin; Somatostatin; Spectrometry, Mass, Electrospray Ionization; Statistics, Nonparametric; Time Factors

In previous works, we reported that Hyp (hyperin) showed strong analgesic effect, and inhibited discharges induced by multianalgesics, but without anesthetic action. In this study, the analgesic mechanism of Hyp was further investigated. In the tail-flick test in mice, EGTA was shown to markedly enhance the analgesic effect of Hyp and shift the dose-effect curve to the upper-left. CaCl2 significantly antagonized the effect of Hyp and shifted the dose-effect curve to the lower-right. In the afferent discharges induced by analgesics, EGTA markly elevated while cacl2 lowered the effect of Hyp. It was also found that A23187, which promote influx of Ca2+, could antagonize the effect of Hyp. In the frog sciatic nerves, we found that Hyp could significantly inhibit influx of Ca2+. This finding suggests that the analgesic effect of Hyp may have close relationship with the reduction of calcium in afferent nerve endings.

Topics: Analgesics; Animals; Anura; Calcium; Electrophysiology; Female; Flavonoids; Male; Mice; Pain; Quercetin; Rabbits; Sciatic Nerve; Sensory Thresholds