Antinociceptive activity of 3-O-β-d-glucopyranosyl-23,24-dihydrocucurbitacin F from Hintonia standleyana (Rubiaceae)

Oral administration of a MeOH-CH₂Cl₂ (1:1) extract of the stem bark of Hintonia standleyana (HSE) produced a dose-dependent antinociceptive effect when tested in mice using the writhing (150-750 mg/kg) and the hot-plate (150-600 mg/kg) models. From the active extract 3-O-β-d-glucopyranosyl-23,24-dihydrocucurbitacin F (GDHCF), 5-O-[β-d-apiofuranosyl-(1→6)-β-d-glucopyranosyl]-7-methox y-3′,4′-dihydroxy-4-phenylcoumarin (AG4-PC) and desoxycordifolinic acid (DCA) were isolated. GDHCF (10-100 mg/kg, p.o.) significantly reduced acetic acid-induced abdominal contortions and increased the hot-plate latency in comparison to vehicle-treated mice. Metamizol (50-100 mg/kg) and morphine (2.5-5 mg/kg) were used as positive controls, respectively. GDHCF-induced antinociception was partially blocked by naloxone (1 mg/kg, i.p.), l-NAME (150 mg/kg, i.p.) and glibenclamide (10 mg/kg, i.p.) suggesting that its pharmacological effect could be due to the activation of the nitric oxide pathway, followed by the opening of the ATP-sensitive K⁺ channels, as well as an activation of the opioid receptors.