Insights into Chemopreventive Effects of Rosmarinic Acid Against Aflatoxin B1-Induced Genotoxic Effects
Year: 2025
Type: article
Abstract: 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.
Source: Foods
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,499
Awards: Computer-aided framework for the systematic synthesis, design, and integration of flow chemistry and microprocesses into sustainable production systems targeting Power-to-X, Understanding the mechanisms and prevention of aggregation of biopharmaceutic proteins, BBMRI, Multi-omic analysis of NFkB-mediated signaling in multiple sclerosis, Unlocking the Selective Catalytic Conversion Processes of CO2 to Ethanol – UliSess, Chemical Carcinogenesis and Neurodegeneration: Molecular-Level Mechanistic Impact of Microwave Irradiation, Optical Chemical/Bio Sensor Systems (OPTISENS), Production, Isolation and Formulation of Health Beneficial Substances from Helichrysum Italicum for Applications in Cosmetic Industry, Computationally intensive complex systems, Unveiling the Analgesic Potential of Herkinorin: A Comprehensive Approach to Designing Safer Opioids, Mycotoxins and their complex mixtures: relevance for human health hazard from contaminated food, Ecotoxicology, toxicogenomics and carcinogenesis, Mechanistic insights into the anticarcinogenic, antioxidative, and antimicrobial activity of natural polyphenolic compounds from Helichrysum italicum, Non-invasive multi-omics biomarkers in immune cells subtypes for personalized medicine in childhood asthma and molecular mechanisms of non-response to inhaled corticosteroids, Separation Processes and Product Design, Library of opioid binding patterns in correlation with their adverse side effects, Coronaviral therapeutic target mutagenesis platform for communal treatment evaluation and the development of pan-coronavirus inhibitors, Development of Electrochemical Biosensor for Detection of Methylmercury, ProBiS-Fold approach for binding site detection for whole structural human proteome in drug discovery
OpenAlex ID: W4411344839