Currently, the consumption of dietary supplement containing botanical products and foods is growing at a remarkable speed, in terms of the promotion of health or prevention and treatment of diseases. The extract from Hypericum perforatum (St. John's wort, SJW) possess clinical efficacy in the therapy of mild to moderate depression. 1,2) The most important constituents of SJW are phloroglucinols such as hyperforin and pseudohyperforin, naphthodianthrones such as hypericin and pseudohypericin, in addition to flavonoids such as rutin, quercetin, quercitrin. Several in vitro studies have indicated that SJW and hyperforin may act via a blockade of reuptake of serotonin, noradrenaline and dopamine in similar manner as most of the current antidepressants such as tricyclic antidepressants, [3][4][5] which have been known to exhibit antinociceptive properties by monoamine reuptake blockade.Harpagophytum procumbens extract (HPE) and Grape seed proanthocyanidins extract (GSPE) have been reported to exert anti-inflammatory activity in rodents.6-8) Harpagophytum procumbens commonly known as Devil's claw is an herbaceous plant, growing specifically in Southern Africa. Preparations of its secondary roots contain iridoid glycosides, mainly harpagoside, harpagogide and procumbide. HPE have been shown to possess clinical efficacy in the treatment of degenerative rheumatoid arthritis, osteoarthritis and tendonitis. [6][7][8] In addition, experimental study has revealed antiinflammatory activity of HPE in Freund's adjuvant-induced arthritis model. 9) Proanthocyanidins are naturally occurring polyphenolic compounds widely available in fruits, vegetables, nuts, seeds, flowers and bark. Grape seed proanthocyanidins, a combination of biologically active polyphenolic flavonoids including oligomeric proanthocyanidins, have been shown to exert a novel spectrum of biological, pharmacological, therapeutic and chemoprotective properties against oxygen free radicals and oxidative stress. GSPE protects against free radicals models and has exhibited superior antioxidant performance as compared to vitamin C, E and b-carotene.
10)Previous studies with antidepressant activity of SJW and anti-inflammatory effects of HPE and GSPE have led to the idea that these herbal products exert antinociceptive action. Thus, the aim of this study was to clarify the antinociceptive properties of SJW, HPE and GSPE after oral administration to mice with mechanisms that might potentially underlie these activities. The effects of these herbal extracts on the antinociception and plasma and brain concentrations of morphine were also examined.
MATERIALS AND METHODSDrugs SJW and HPE were kindly donated by Indena (Milan, Italy). SJW was standardized to the content of hypericin (0.3%) and hyperforin (3.2%) and HPE was also standardized to the content of harpagoside (1.9%). GSPE was kindly supplied by Kikkoman Co. (Chiba, Japan), and standardized to the content of proanthocyanidin (83.9%). Morphine hydrochloride was purchased from Takeda Pharmaceutical Co. (Osaka, Japan). A...