Xandy Melissa Rodríguez-Mesa

Background: Breast and prostate cancers remain a major global health burden, driving the search for novel therapeutic candidates with improved efficacy and reduced toxicity. Objective:To evaluate the cytotoxic and pro-apoptotic effects of the essential oil (EO) and supercritical CO2 extract (SC-CO₂) of Origanum vulgare L. on breast cancer (MCF-7, MDA-MB231) and prostate cancer (PC-3) cell lines, to explore potential molecular mechanisms using molecular docking and molecular dynamics simulations. Methods: EO was obtained by hydrodistillation, whereas SC-CO₂ was produced using supercritical carbon dioxide (SC-CO₂) extraction. Chemical characterization of EO and SC-CO₂ was performed by gas chromatography–mass spectrometry (GC–MS). Cytotoxic activity was assessed using the MTT assay, and the half-maximal inhibitory concentration (IC₅₀) was determined. Flow cytometry evaluated the type of cell death and associated morphological changes, followed by statistical analysis using one-way ANOVA. Results: GC-MS profiling revealed carvacrol, thymol methyl ether, and β-caryophyllene as the major components of the EO and the SC-CO₂. The EO showed moderate to weak cytotoxicity across all cell lines, with IC₅₀ values ranging from 25.41 to 106.5 μg/mL (IC₅₀ = 25.41–106.5 μg/mL), whereas the SC-CO₂ displayed moderate activity only against PC-3 cells (IC₅₀ = 22.9 μg/mL). Both treatments reduced viable cell counts in a dose-dependent manner, induced apoptosis, and altered cell size and granularity, as observed by flow cytometric analysis. Molecular docking and MM-GBSA calculations revealed strong binding affinities of carvacrol for p53 and of β-caryophyllene and thymol methyl ether for Bcl-2. Molecular dynamics simulations demonstrated stable ligand–protein complexes, with root-mean-square deviation (RMSD) values remaining within acceptable ranges throughout the simulation period. Conclusions: Thesein vitro and computational findings suggest that EO and SC-CO₂ from O. vulgare may exert anticancer effects through apoptosis induction, supporting further mechanistic investigations and in vivo validation.

Different communities around the world traditionally use Bidens pilosa L. for medicinal purposes, mainly for its anti-inflammatory, antinociceptive, and antioxidant properties; it is used as an ingredient in teas or herbal medicines for the treatment of pain, inflammation, and immunological disorders. Several studies have been conducted that prove the immunomodulatory properties of this plant; however, it is not known whether the immunomodulatory properties of B. pilosa are mediated by its ability to modulate antigen-presenting cells (APCs) such as macrophages (MØs) and dendritic cells (DCs) (through polarization or the maturation state, respectively). Different polar and non-polar extracts and fractions were prepared from the aerial part of B. pilosa. Their cytotoxic and immunomodulatory effects were first tested on human peripheral blood mononuclear cells (PBMCs) and phytohemagglutinin (PHA)-stimulated PBMCs, respectively, via an MTT assay. Then, the non-cytotoxic plant extracts and fractions that showed the highest immunomodulatory activity were selected to evaluate their effects on human MØ polarization and DC maturation (cell surface phenotype and cytokine secretion) through multiparametric flow cytometry. Finally, the chemical compounds of the B. pilosa extract that showed the most significant immunomodulatory effects on human APCs were identified using gas chromatography coupled with mass spectrometry. The petroleum ether extract and the ethyl acetate and hydroalcoholic fractions obtained from B. pilosa showed low cytotoxicity and modulated the PHA-stimulated proliferation of PBMCs. Furthermore, the B. pilosa petroleum ether extract induced M2 polarization or a hybrid M1/M2 phenotype in MØs and a semi-mature status in DCs, regardless of exposure to a maturation stimulus. The immunomodulatory activity of the non-polar (petroleum ether) extract of B. pilosa on human PBMC proliferation, M2 polarization of MØs, and semi-mature status in DCs might be attributed to the low–medium polarity components in the extract, such as phytosterol terpenes and fatty acid esters.

Bidens pilosa L. has been used in different parts of the world mainly to treat diseases associated with immune response disorders, such as autoimmunity, cancer, allergies, and infectious diseases. The medicinal properties of this plant are attributed to its chemical components. Nevertheless, there is little conclusive evidence that describes the immunomodulatory activity of this plant. In this review, a systematic search was carried out in the PubMed-NLM, EBSCO Host and BVS databases focused on the pre-clinical scientific evidence of the immunomodulatory properties of B. pilosa. A total of 314 articles were found and only 23 were selected. The results show that the compounds or extracts of Bidens modulate the immune cells. This activity was associated with the presence of phenolic compounds and flavonoids that control proliferation, oxidative stress, phagocytosis, and the production of cytokines of different cells. Most of the scientific information analyzed in this paper supports the potential use of B. pilosa mainly as an anti-inflammatory, antioxidant, antitumoral, antidiabetic, and antimicrobial immune response modulator. It is necessary that this biological activity be corroborated through the design of specialized clinical trials that demonstrate the effectiveness in the treatment of autoimmune diseases, chronic inflammation, and infectious diseases. Until now there has only been one clinical trial in phase I and II associated with the anti-inflammatory activity of Bidens in mucositis.