Pharmacological disadvantages in the spasmolytic effects by using the mixture known as “three toronjiles” in folk medicine

In Mexico, Agastache mexicana subsp. mexicana (PT) and subsp. xolocotziana (WT), and Dracocephalum moldavica (BT), are used together as the “three toronjiles” to treat gastrointestinal spasms. To evaluate if the spasmolytic activity of these three medicinal species is better in combination or in an individual manner. Spasmolytic effect of PT, WT and BT alone or combinate were evaluated in rings of the guinea-pig ileum contracted with potassium chloride (KCl), electrical field stimulation (EFS), or acetylcholine (ACh). Chemical analysis by thin layer and ultra-high pressure liquid chromatography of the aqueous extracts of each species were done for their comparison, and their acute toxicity were determined in mice. PT and WT diminished in a dose-dependent manner the contractions induced by KCl, EFS, and ACh. Whereas BT did not altered contractions in any experimental protocol. A combination of the PT (EC50) and WT (EC50) diminished the contractions induced by KCl or EFS. Interestingly, the addition of BT extract (10 μg/ml) to the combination (PT EC30 + WT EC30) blocked the inhibitory effect produced on the contracted tissue in the presence of KCl, EFS, or ACh. Moreover, addition of BT extract (100 μg/ml) to the same combination blocked the inhibitory effect on the pre-contracted tissue only in the presence of EFS. None of the aqueous extracts produced toxicity in its individual administration in mice. Chemical analysis demonstrated similarities between PT and WT, but differences with BT. The results of this study confirmed that either combined or by themselves aqueous extracts of PT and WT produced a spasmolytic action on guinea pig ileum, suggesting that this combination of medicinal plants could relieve gastrointestinal diseases in human, but when BT aqueous extract is added to those obtained with PT and WT, the spasmolytic activity diminished or even was blocked. Our results give evidence that mixture of several plants might produce disadvantages in the medicinal properties of their individual activity. [Display omitted] •PT and WT, but not BT, induced spasmolytic effects in individual administration.•A synergistic interaction was observed in the combination of PT + PW.•BT antagonized the spasmolytic effect of PT + PW.•PT, WT and BT did not produce acute toxicity.