20.500.12556/DiRROS-22854 Insights into chemopreventive effects of rosmarinic acid against aflatoxin B1-induced genotoxic effects In this study, the chemopreventive effects of rosmarinic acid (RA), a major phenolic acid of the plant Rosmarinus officinalis L., against the carcinogenic naturally occurring mycotoxin aflatoxin B1 (AFB1) were investigated using both in silico and in vitro approaches. The in silico investigation of the chemical reactions between rosmarinic acid and the carcinogenic metabolite of AFB1, aflatoxin B1 exo-8,9-epoxide (AFBO), was conducted by activation free energies calculations with DFT functionals M11-L and MN12-L, in conjunction with the 6-311++G(d,p) flexible basis set and implicit solvation model density (SMD), according to a newly developed quantum mechanics-based protocol for the evaluation of carcinogen scavenging activity (QM-CSA). Following the computational analyses, the chemoprotective effects of RA were further studied in vitro in human hepatocellular carcinoma HepG2 cells by analyzing its influence on AFB1-induced genotoxicity using a comet assay, γH2AX, and p-H3, while its impact on cell proliferation and cell cycle modulation was assessed using flow cytometry. Our computational results revealed that the activation free energy required for the reaction of RA with AFBO (14.86 kcal/mol) is significantly lower than the activation free energy for the competing reaction of AFBO with guanine (16.88 kcal/mol), which indicates that RA acts as an efficient natural scavenger of AFBO, potentially preventing AFB1-specific DNA adduct formation. The chemoprotective activity of RA was confirmed through in vitro experiments, which demonstrated a statistically significant (p < 0.05) reduction in AFB1-induced single- and double-strand breaks in HepG2 cells exposed to a mixture of AFB1 and RA at non-cytotoxic concentrations. In addition, RA reversed the AFB1-induced reduction in cell proliferation. rosmarinic acid aflatoxin B1 chemopreventive effects antigenotoxic effects density functional theory chemical carcinogen scavenger toxicology rožmarinska kislina aflratoksin B1 kemoprotektivni učinki antigenotoskični učinki toksikologija true false true Angleški jezik Slovenski jezik Neznano 2025-07-03 16:28:06 2025-07-03 16:28:06 2025-10-24 03:52:20 0000-00-00 00:00:00 2025 0 0 Soavtorji: Matjaž Novak, Martina Štampar, Alja Štern, Bojana Žegura and Urban Bren; Nasl. z nasl. zaslona; Opis vira z dne 3. 7. 2025; str. [1]-17 art. no. ǂ2111 iss. 12 Jun. 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2025-06-16 615.9 2304-8158 10.3390/foods14122111 241332995 https://doi.org/10.3390/foods14122111 1 f2a2c115-5819-11f0-8080-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=33248 RAZ_Furlan_Veronika_2025.pdf RAZ_Furlan_Veronika_2025.pdf 1 1E545E41B201D6B9041FA2E96E908A93 6547a18507726cef1f7d0bc18cd39eded73c707f1b16feaa9cea27498b17f69f 2e26a92d-581a-11f0-8080-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=33249 foods-14-02111-s001.zip foods-14-02111-s001.zip Dopolnilne informacije Supplementary materials 1 7A75CB92CDF722848BD23140E88C6FB0 04f40520286c1226225f9cfecf01eb97c5c37de30f0003941315059eae2686e7 146ba441-58a5-11f0-8080-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=33250 Nacionalni inštitut za biologijo 0 0 0