Pharmacological potential of chalepensin from Ruta chalepensis L.: Acute toxicity and in vivo antitumor activity in the L5178Y-R murine model.

[ETHNOPHARMACOLOGICAL RELEVANCE] Ruta chalepensis L. (rue) is a medicinal plant commonly used in folk medicine and is known to contain bioactive secondary metabolites with pharmacological potential. Among these, chalepensin has been previously described to exhibit antitumor activity in vitro; however, its in vivo efficacy and safety profile remain poorly characterized.

[AIM OF THE STUDY] To evaluate the in vitro and in vivo antitumor activity of chalepensin against L5178Y-R murine lymphoma and to assess its acute toxicity profile.

[MATERIALS AND METHODS] Chalepensin was isolated from the leaves and stems of R. chalepensis. Cytotoxic activity was determined in vitro with the MTT assay against tumor and normal cell lines. In silico analyses were performed to predict pharmacokinetic properties and explore potential molecular interactions. Acute toxicity was assessed in BALB/c mice following intraperitoneal administration of chalepensin (100 and 1000 mg/kg). Antitumor efficacy was evaluated in BALB/c mice bearing L5178Y-R lymphoma by monitoring tumor volume and survival.

[RESULTS] Chalepensin exhibited potent cytotoxic activity against L5178Y-R cells (IC = 8.1 μg/mL; SI = 66.5). In silico analyses predicted favorable pharmacokinetic properties. Acute toxicity studies revealed no mortality, clinical signs of toxicity, or significant alterations in biochemical and hematological parameters. In vivo, chalepensin induced a significant reduction in tumor volume between days 10 and 20 (p < 0.05) and significantly prolonged mean survival time, showing comparable or superior efficacy to vincristine under the tested conditions. Molecular docking suggested a preferential interaction with the Cyclin A2-CDK2 complex, supporting a potential cytostatic mechanism consistent with the observed in vivo effects.

[CONCLUSION] Chalepensin demonstrates promising antitumor activity against L5178Y-R murine lymphoma, along with a favorable acute toxicity profile. These findings support its potential for further preclinical development and warrant additional studies to elucidate its molecular mechanisms and long-term safety.