An Isobolographic Analysis of the Antinociceptive Effect of Salvia hispanica L. in Combination with Citrus × latifolia in Rats.

This study aimed to evaluate the antinociceptive effect of Salvia hispanica L. seeds, Citrus × latifolia (Lime) juice, and the interaction of their combination in rats using the writhing test. Dose-response curves were constructed for an n-hexane extract of S. hispanica seeds (100-300 mg/kg; p.o.) and C. × latifolia juice (10-300 mg/kg; p.o.) administered individually or in combination to rats subjected to 1% acetic acid-induced writhing. Isobolographic analysis was used to assess the interaction between the combinations. Results showed that both medicinal plants exhibited dose-dependent antinociceptive effects. The antinociceptive effect of C. × latifolia (ED50 = 43.95 ± 1.9 mg/kg) exhibited greater potency than S. hispanica (ED50 = 112.9 ± 2.0 mg/kg). Their combination (1:1 ratio) showed a synergistic antinociceptive effect (Zexp = 4.9 ± 0.6 mg/kg vs. Zadd = 83.5 ± 1.7 mg/kg). Both extracts were non-toxic, according to the OECD-423 test. Antioxidant activity may have contributed to the observed antinociceptive synergy. This study demonstrates that the synergistic antinociceptive effects suggest that combining S. hispanica and C. × latifolia may be a promising therapeutic approach for managing inflammatory and visceral pain with potential clinical utility.