Synergistic interactions between the antinociceptive effect of Rhodiola rosea extract and B vitamins in the mouse formalin test.
OBJECTIVE
In this study, the pharmacological interactions between a Rhodiola rosea ethanol extract and B-vitamins such as thiamine (B1), riboflavine (B2), pyridoxine (B6), cyanocobalamin (B12) and a mixture of vitamins B1+B6+B12 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 B1+B6+B12 by using the ED30 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 (ED50=81 mg/kg, p.o.) was significant and reverted in the presence of antagonists of the 5-HT1A, 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 ED30 values were significantly smaller than those calculated theoretically.


CONCLUSIONS
These results provide evidence that a Rhodiola rosea ethanol extract in combination with B-vitamins produces a significant diminution in the nociceptive response in a synergistic manner, which is controlled by various mechanisms. These findings could aid in the design of clinical studies and suggest that these combinations could be applied for pain therapy.
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, DF 11340, Mexico.
Rosa Mariana
RM
Montiel-Ruiz
María Eva
ME
González-Trujano
Myrna
M
Déciga-Campos
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D005260:Female; D005557:Formaldehyde; D051379:Mice; D008813:Mice, Inbred ICR; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D029771:Rhodiola; D014803:Vitamin B Complex / Q000494:pharmacology / Q000627:therapeutic use*
D000700:Analgesics; D010936:Plant Extracts; D014803:Vitamin B Complex; D005557:Formaldehyde
Antinociception; B-vitamin; Isobolographics; Plant-drug interaction; Rhodiola rosea; Synergism