Abstract
The present study addresses the chemoprotective effects of xanthohumol (XN), a prenylated flavonoid found in the female inflorescences (hops) of the plant Humulus lupulus L., against the carcinogenic food contaminant aflatoxin B1 (AFB1). The chemical reactions of XN and its derivatives (isoxanthohumol (IXN), 8-prenylnaringenin (8-PN), and 6-prenylnaringenin (6-PN)) with the AFB1 metabolite, aflatoxin B1 exo-8,9-epoxide (AFBO), were investigated in silico, by calculating activation free energies (ΔG‡) at the Hartree–Fock level of theory in combination with the 6-311++G(d,p) basis set and two implicit solvation models. The chemoprotective effects of XN were investigated in vitro in the metabolically competent HepG2 cell line, analyzing its influence on AFB1-induced cytotoxicity using the MTS assay, genotoxicity using the comet and γH2AX assays, and cell cycle modulation using flow cytometry. Our results show that the ΔG‡ required for the reactions of XN and its derivatives with AFBO are comparable to the ΔG‡ required for the reaction of AFBO with guanine, indicating that XN, IXN, 8-PN, and 6-PN could act as scavengers of AFBO, preventing DNA adduct formation and DNA damage induction. This was also reflected in the results from the in vitro experiments, where a reduction in AFB1-induced cytotoxicity and DNA single-strand and double-strand breaks was observed in cells exposed to combinations of AFB1 and XN, highlighting the chemoprotective effects of this phytochemical.
Highlights
Nutrition and diet are fundamentally involved in human cancer etiology and prevention
XN was evaluated for its chemoprotective properties against the carcinogenic mycotoxin Aflatoxin B1 (AFB1), which, upon ingestion, is converted to the ultimate carcinogen AFBO and other hydroxylated metabolites by the cytochrome P450 enzymes (CYP450) isoforms CYP3A4 and CYP1A2 [26]
XN is metabolized by CYP450s (Figure 1)
Summary
Nutrition and diet are fundamentally involved in human cancer etiology and prevention. The human diet is highly complex and versatile, containing numerous potentially mutagenic and carcinogenic ingredients, compounds, and contaminants [1], as well as various antioxidants and potentially chemoprotective and anticarcinogenic bioactive chemicals [2,3,4,5]. Prenylated flavonoids comprise a group of dietary phytochemicals with various beneficial health-related effects [6]. In the range of 0.03–0.39 mg/L and total prenylated flavonoids, mainly the flavone isoxanthohumol (IXN), at concentrations of up to 9.47 mg/L [8]. Some brands offer XN enriched beers, which can be achieved by prevention of XN isomerization through specialized brewing techniques and the late addition of hops at high quantities, which can result in XN concentrations of more than 10 mg/L in the finished beer [10]
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