Exploring the antiprotozoal and anticancer potential of medicinal Hypericum species through molecular and pharmacological approaches

• H. scabrum and H. perforatum showed selective antiparasitic effects . • Hypericum extracts reduced cancer cell viability, notably in HT-29 cells. • Extracts increased BAX expression and decreased ODC in cancer cells. • Molecular docking highlights rutin, hesperidin, kaempferol, and gallic acid. • Kaempferol and gallic acid had the best ADME and drug-like properties. Hypericum scabrum and Hypericum perforatum are traditionally used medicinal plants known for their therapeutic properties, including wound healing and mood regulation. This study aims to validate their traditional uses by investigating their anticancer and antiparasitic activities. To characterize the bioactive compounds of H. scabrum and H. perforatum extracts and evaluate their potential anticancer and antiparasitic mechanisms, gene expression profiling, and in silico modeling. Ethanolic extracts of both species were analyzed to determine phytochemical composition. Anticancer effects were tested on colon adenocarcinoma and lung carcinoma cells using MTT assay and flow cytometry. Antiparasitic activity was assessed against Leishmania amazonensis, Trypanosoma cruzi, Acanthamoeba castellanii , and Naegleria fowleri . Gene expression of apoptosis and polyamine synthesis markers were evaluated by RT-PCR. Molecular docking and ADME/Tox predictions were conducted to identify active compounds and assess their drug-likeness. Both extracts reduced cancer cell viability and induced apoptosis in cancer cells. H. scabrum showed potent activity against T. cruzi , L. amazonensis , and Acanthamoeba , while H. perforatum was active against N. fowleri, T. cruzi , and L. amazonensis . Gene expression analysis revealed upregulation of pro-apoptotic BAX and downregulation of ODC. Molecular docking identified rutin, hesperidin, kaempferol, and gallic acid as key binders to cancer and parasite target proteins. Kaempferol and gallic acid displayed favorable ADME profiles. The study supports the traditional use of H. scabrum and H. perforatum by confirming their antiparasitic and anticancer potential. Kaempferol and gallic acid emerge as promising candidates for drug development.