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The use of alternative medicine to treat pain has been increased, and the combination of several medicinal plants for its relief is a common practice in traditional medicine. The present study is aimed at determining whether a combination of  Syzygium aromaticum  ( S. aromaticum ) and  Rosmarinus officinalis  L. ( R. officinalis ) potentiates their antinociceptive and anti-inflammatory effects. These effects were explored using the formalin and carrageenan assays in rats, respectively. Animals received local pretreatment with  S. aromaticum  oil or  R. officinalis  ethanolic extract (0.1–100  μ g/paw) alone or combined in a 1 : 1 rate. Concentration-response curves were built to compare pharmacological responses after an individual administration of  S. aromaticum ,  R. officinalis , or their combination. The pharmacological interaction was investigated by an isobolographic study using the EC 50  of each component in a fixed 1 : 1 ratio.  S. aromaticum  and  R. officinalis  administered alone showed significant and concentration-dependent antinociceptive and anti-inflammatory effects, but  R. officinalis  was more potent than  S. aromaticum  in both the antinociceptive and anti-inflammatory effects (EC 50  = 7.96 ± 0.6  μ g/paw vs. EC 50  = 41.6 ± 1.7  μ g/paw; EC 50  = 1.97 ± 0.3  μ g/paw vs. EC 50  = 26.9 ± 2.5  μ g/paw, respectively). The isobolographic analysis of the combination of these species in a 1 : 1 ratio showed a synergistic interaction between  S. aromaticum  and  R. officinalis  since  Z  mix  (experimental value) was lower than  Z  add  (theoretical value) for both the antinociceptive effect ( Z  mix  = 0.45 ± 0.1 <  Z  add  = 24.8 ± 1.3) and the anti-inflammatory effect ( Z  mix  = 5.2 ± 0.6 <  Z  add  = 14.4 ± 2.2), suggesting a potentiation for both pharmacological effects. These results prove evidence of the efficacy of mixture herb-herb used in folk medicine for pain therapy. It also emphasizes the requirement of pharmacological studies to explore the efficacy and safety of herb interactions.

Synergistic Herb-Herb Interaction of the Antinociceptive and Anti-Inflammatory Effects of Syzygium aromaticum and Rosmarinus officinalis Combination