Antinociceptive Synergism of Pomegranate Peel Extract and Acetylsalicylic Acid in an Animal Pain Model

Several modern drugs, which are derived from traditional herbal medicine are used in contemporary pharmacotherapy. Currently, the study of drug–plant interactions in pain has increased in recent years, looking for greater efficacy of the drug and reduce side effects. The antinociception induced by intragastric co-administration of the combination of pomegranate peel extract (PoPEx) and acetylsalicylic acid (ASA) was assessed using the isobolographic analysis in formalin test (nociceptive and inflammatory pain). The effective dose that produced 30% of antinociception (ED(30)) was calculated for both drugs from the logarithmic dose–response curves, subsequently generating a curve with the combination on fixed proportions (1:1) of PoPEx and ASA. Through isobolographic analysis, this experimental ED(30) was compared with the calculated theoretical additive ED(30). The result was a synergistic interaction, the experimental ED(30) was significantly smaller (p < 0.05) than the theoretical ED(30). The antinociceptive mechanism of the PoPEx-ASA combination involves the l-Arginine/NO/cGMP pathway, antioxidant capacity, and high content of total phenols. These findings suggest that an interaction between PoPEx and ASA could be a novel treatment for inflammatory and nociceptive pain, also diminish the secondary reactions of ASA.