Chemoprotective Effects of Xanthohumol against the Carcinogenic Mycotoxin Aflatoxin B1

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.

Biological Activities Related to Plant Protection and Environmental Effects of Coumarin Derivatives: QSAR and Molecular Docking Studies

“…Polyphenols, secondary plant metabolites that include phenolic acids, tannins, coumarins, lignins, stilbenes, terpenes, and flavonoids, naturally offer plants protection against abiotic stresses, UV light, pathogens, parasites, and plant predators [ 77 ]. Xanthohumol, a prenylated flavonoid isolated from hops ( Humulus lupulus L.), was proven to have chemoprotective effects against the carcinogenic food contaminant aflatoxin B1 that is produced by the fungi Aspergillus flavus and Aspergillus parasiticus [ 78 ]. Its antimutagenic effect is based on preventing the DNA adduct formation and DNA damage induction.…”

Antimicrobial Properties of Different Hop (Humulus lupulus) Genotypes

“…Namely, hops contain bitter acids, which represent a great portion of dry hop cones and are further divided into α-acids (humulones) and β-acids (lupulones) [ 10 ]. In addition, flavonoids (with the main representative xanthohumol (XH)) also form important hop compounds [ 11 ] that exhibit antimicrobial activities [ 10 , 12 , 13 ] and anticarcinogenic effects [ 14 , 15 ].…”

Phytochemistry and pharmacology of natural prenylated flavonoids

“…The chemoprotective effect of 579 was investigated in vitro in the metabolically competent HepG2 cell line. The results indicated that 579 could act as a scavenger of AFBO, preventing DNA adduct formation and DNA damage induction (Štern et al 2021 ). 579 impaired the PMA-driven migratory and invasive capacity of A549 cells by decreasing the level of MMP-9 expression and concomitantly increasing TIMP-1 protein expression, a specific blocker of PRO-MMP-9 activation.…”