title: Antinociceptive effects of St. John's wort, Harpagophytum procumbens extract and Grape seed proanthocyanidins extract in mice.
abstract: Hypericum perforatum extract (St. John's wort, SJW), Harpagophytum procumbens extract (HPE) and Grape seed proanthocyanidin extract (GSPE) have a broad spectrum of biological activities including antidepressant, anti-inflammatory or anti-oxidant effects. The aim of this study was to clarify antinociceptive properties of SJW, HPE and GSPE in mice with mechanisms that might potentially underlie these activities. Also, the effects of these herbal extracts on the antinociception and plasma and brain concentrations of morphine were examined. Oral pretreatment with SJW (100-1000 mg/kg) and HPE (30-300 mg/kg) attenuated significantly times of licking/biting both first and second phases of formalin injection in mice in the dose-dependent manner, and GSPE (10-300 mg/kg) suppressed second phase. Naloxone (5 mg/kg, s.c.) significantly attenuated antinociceptive effect of HPE but not SJW and GSPE. Formalin injection resulted in significant increase in the content of nitrites/nitrates (NO(x)) in mouse spinal cord. The rise of spinal NO(x) content by formalin was significantly attenuated by HPE and SJW. The pretreatment with SJW significantly potentiated an antinociceptive effect of morphine (0.3 mg/kg, s.c.), although concentrations of morphine in plasma and brain were not significantly changed by these herbal extracts. In conclusion, the present study has shown that SJW, HPE and GSPE exert significant antinociceptive effects in the formalin test of mice. In addition, opioidergic system seems to be involved in the antinociceptive effect of HPE but not SJW and GSPE. Furthermore, SJW potentiates morphine-induced antinociception possibly by pharmacodynamic interaction.
authors.affiliation: Department of Pharmacokinetics and Pharmacodynamics and Global COE Program, School of Pharmaceutical Sciences, University of Shizuoka, Suruga-ku, Shizuoka, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Uchida
authors.forename: Keita
authors.initials: K
authors.lastname: Hirai
authors.forename: Junya
authors.initials: J
authors.lastname: Hatanaka
authors.forename: Junko
authors.initials: J
authors.lastname: Hanato
authors.forename: Keizo
authors.initials: K
authors.lastname: Umegaki
authors.forename: Shizuo
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000493:pharmacokinetics; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D031684:Harpagophytum / Q000737:chemistry*; D006358:Hot Temperature; D020902:Hypericum / Q000737:chemistry*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000493:pharmacokinetics; D009043:Motor Activity / Q000187:drug effects; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010147:Pain Measurement / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology; D044945:Proanthocyanidins / Q000302:isolation & purification / Q000494:pharmacology*; D011930:Reaction Time / Q000187:drug effects; D012639:Seeds / Q000737:chemistry; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D027843:Vitis / Q000737:chemistry*
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D009566:Nitrates; D009573:Nitrites; D010936:Plant Extracts; D044945:Proanthocyanidins; D005557:Formaldehyde; D009020:Morphine