Abstract

Aim In this study, the pharmacological interactions between a Rhodiola rosea ethanol extract and B-vitamins such as thiamine (B 1 ), riboflavine (B 2 ), pyridoxine (B 6 ), cyanocobalamin (B 12 ) and a mixture of vitamins B 1 + B 6 + B 12 was investigated in the mouse formalin test.

Methods Individual dose response curves of the Rhodiola rosea ethanol extract, as well as B-vitamins alone or in a mixture were evaluated in mice in which nociception was induced with 2% formalin intraplantarly. The antinociceptive mechanisms of the Rhodiola rosea were investigated by exploring the role of the opioid and serotonin receptors and the nitric oxide pathway. Isobolographic analysis was used to evaluate the pharmacological interactions between the Rhodiola rosea ethanol extract and each B-vitamin individually or the mixture of vitamins B 1 + B 6 +B 12 by using the ED 30 and a fixed 1:1 ratio combination.

Results Administration of the Rhodiola rosea extract alone or in combination with all of the vitamins produced a significant and dose-dependent antinociceptive response. The antinociceptive effect of the Rhodiola rosea extract (ED 50 = 81 mg/kg, p.o.) was significant and reverted in the presence of antagonists of the 5-HT 1A , GABA/BDZs and opioid receptors and by blocking mediators of the nitric oxide/cGMP/K+ channels pathway. Isobolograms demonstrate that all of the combinations investigated in this study produced a synergistic interaction experimental ED 30 values were significantly smaller than those calculated theoretically.