TY - JOUR
T1 - Synergistic interactions between the antinociceptive effect of Rhodiola rosea extract and B vitamins in the mouse formalin test
AU - Montiel-Ruiz, Rosa Mariana
AU - González-Trujano, María Eva
AU - Déciga-Campos, Myrna
N1 - Funding Information:
This work was supported by an SIP-IPN 20130857 grant (MD-C). This work is part of the PhD dissertation of Montiel-Ruiz Rosa Mariana. Montiel-Ruiz is a Consejo Nacional de Ciencia y Tecnología (CONACYT) and Programa Integral de Fortalecimiento Institucional-Instituto Politécnico Nacional (PIFI-IPN) fellow.
PY - 2013/11/15
Y1 - 2013/11/15
N2 - Aim In this study, the pharmacological interactions between a Rhodiola rosea ethanol extract and B-vitamins such as thiamine (B1), riboflavine (B2), pyridoxine (B6), cyanocobalamin (B 12) and a mixture of vitamins B1 + B6 + 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 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.
AB - Aim In this study, the pharmacological interactions between a Rhodiola rosea ethanol extract and B-vitamins such as thiamine (B1), riboflavine (B2), pyridoxine (B6), cyanocobalamin (B 12) and a mixture of vitamins B1 + B6 + 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 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.
KW - Antinociception
KW - B-vitamin
KW - Isobolographics
KW - Plant-drug interaction
KW - Rhodiola rosea
KW - Synergism
UR - http://www.scopus.com/inward/record.url?scp=84886097614&partnerID=8YFLogxK
U2 - 10.1016/j.phymed.2013.07.006
DO - 10.1016/j.phymed.2013.07.006
M3 - Artículo
C2 - 23920277
SN - 0944-7113
VL - 20
SP - 1280
EP - 1287
JO - Phytomedicine
JF - Phytomedicine
IS - 14
ER -