Infusions of Valeriana pilosa are commonly used in Peruvian folk medicine for treating gastrointestinal disorders. This study aimed to investigate the spasmolytic and antispasmodic effects of Valeriana pilosa essential oil (VPEO) on rat ileum. The basal tone of ileal sections decreased in response to accumulative concentrations of VPEO. Moreover, ileal sections precontracted with acetylcholine (ACh), potassium chloride (KCl), or barium chloride (BaCl₂) were relaxed in response to VPEO by a mechanism that depended on atropine, hyoscine butylbromide, solifenacin, and verapamil, but not glibenclamide. The results showed that VPEO produced a relaxant effect by inhibiting muscarinic receptors and blocking calcium channels, with no apparent effect on the opening of potassium channels. In addition, molecular docking was employed to evaluate VPEO constituents that could inhibit intestinal contractile activity. The study showed that α-cubebene, β-patchoulene, β-bourbonene, β-caryophyllene, α-guaiene, γ-muurolene, valencene, eremophyllene, and δ-cadinene displayed the highest docking scores on muscarinic acetylcholine receptors and voltage-gated calcium channels, which may antagonize M₂ and/or M₃ muscarinic acetylcholine receptors and block voltage-gated calcium channels. In summary, VPEO has both spasmolytic and antispasmodic effects. It may block muscarinic receptors and calcium channels, thus providing a scientific basis for its traditional use for gastrointestinal disorders.

Juglans neotropica (Peruvian walnut) has been widely used by Andean populations in the form of infusions and decoctions for its antioxidant, hypoglycemic, hepatoprotective, antifungal, and antibacterial properties. This study aimed to investigate the effect of Juglans neotropica extract (JNE) on the spasmolytic activity in rat ileum. Our experiments demonstrated that JNE displayed spasmolytic activity at high concentrations, but did not exhibit antispasmodic effects. Additionally, we determined the juglone concentration in JNE by HPLC-DAD, synthesized juglone using green chemistry and compared its spasmolytic activity with that displayed by JNE. Juglone displayed spasmolytic activity on isolated rat ileal sections. Juglone produced a relaxant effect after contraction by a mechanism involving the inhibition of M₂ and M₃ muscarinic receptors and the blockade of calcium channels, with no apparent effect on the opening of potassium channels. Finally, in silico molecular docking analyses showed that juglone displayed high docking scores for M₂ and M₃ muscarinic acetylcholine receptors and Ca_V1.2 voltage-gated calcium channels. In summary, JNE exhibits a spasmolytic, but not an antispasmodic, effect, whereas juglone demonstrates both spasmolytic and antispasmodic activities. These findings provide a scientific basis for the potential use of juglone for managing intestinal hypercontractility disorders. Further research is needed to elucidate the precise molecular interactions to explore its therapeutic applications in gastrointestinal dysfunction.