Mechanistic Insights into the Antispasmodic and Anti‐Inflammatory Activities of Dysphania ambrosioides L. Hydroethanolic Extract: A Combined In Vitro, In Vivo, and In Silico Approach

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Dysphania ambrosioides L ., is commonly used in traditional medicine to treat gastrointestinal (GI) disorders and fever. In this context, this present study aimed to evaluate the antispasmodic and anti‐inflammatory activities of its hydroethanolic extract. The antispasmodic activity and underlying mechanism of action were evaluated on the jejunal part of the rat intestine precontracted with potassium chloride. Additionally, anti‐inflammatory activity was assessed both in vitro and in vivo. Subsequently, molecular docking was performed to validate these pharmacological properties by evaluating the interaction of the predominant bioactive compounds present in the extract with the active site involved in relevant pharmacological pathways. In addition, their pharmacokinetic profiles were investigated through ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analysis. The hydroethanolic extract demonstrated a concentration‐dependent spasmolytic response on isolated rat jejunum, with an IC 50 of 1.17 ± 0.11 mg/mL, blocking L ‐type calcium channels at a concentration of 2 mg/mL. Moreover, it exhibited significant anti‐inflammatory activity by inhibiting protein denaturation, with an IC 50 of 1.35 ± 0.04 mg/mL, and substantially reducing edema induced by phenol and carrageenan in animal models. Molecular docking studies revealed that the bioactive compounds of D. ambrosioides interact with target active sites associated with antispasmodic and anti‐inflammatory activities, thereby supporting the in vitro and in vivo findings. Moreover, these compounds comply with Lipinski's rule of five, highlighting their potential for therapeutic development. The findings of this study provide scientific validation for the traditional use of D. ambrosioides in managing intestinal disorders and inflammation, underscoring its potential as a promising candidate for future therapeutic applications.