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

## TL;DR

This study shows that combining Salvia hispanica and Citrus × latifolia has a stronger pain-relieving effect in rats than using either alone.

## Contribution

The novel finding is the synergistic antinociceptive effect of Salvia hispanica and Citrus × latifolia combination in a rat model.

## Key findings

- Citrus × latifolia showed greater antinociceptive potency than Salvia hispanica.
- The 1:1 combination of the two plants exhibited a synergistic effect in pain relief.
- The combination was non-toxic and may have antioxidant contributions to its effect.

## Abstract

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.