Abstract:
Background: Geraniin, a dehydroellagitannin, is a major
component of the aqueous extract of the aerial parts
of Phyllanthus muellerianus (Kuntze) Exell. (Euphorbi-
aceae). Several Phyllanthus species are traditionally used
for painful disorders. The anti-nociceptive effects of the
aqueous extract of the aerial parts of P. muellerianus and
of geraniin have been scientifically established. The aim
of the paper is to determine whether a combination of
geraniin and diclofenac or geraniin and morphine leads
to better anti-nociceptive effects.
Methods: The nature of the interactions of morphine
and diclofenac with geraniin was evaluated by under-
taking the isobolographic analysis. Mice were treated
with geraniin (3–30 mg/kg), morphine (1–10 mg/kg), and
diclofenac (10–100 mg/kg) to obtain the ED50 values of the
agents in the formalin test. Dose-response curves were
then obtained and analyzed after the co-administration of
geraniin with morphine or diclofenac in fixed ratio (1:1)
combinations based on specific fractions (1/2, 1/4, and 1/8)
of their respective ED50 values for the formalin test.
Results: Geraniin was less potent than morphine but more
potent than diclofenac in the formalin-induced nocic-
eption. The isobolographic analysis of geraniin/morphine
(G/M) and geraniin/diclofenac combinations (G/D) at
different fractions revealed the potentiation of their anti-
nociceptive effects. The degrees of potentiation, which
were calculated as interaction indices, showed synergism
for both combinations in both phase I (G/M: 0.040, G/D:
0.017) and phase II (G/M: 0.004, G/D: 0.002) of the forma-
lin test.
Conclusions: The present study demonstrates synergism
for the co-administration of geraniin with both morphine
and diclofenac.
