Hyperforin Exhibits Antigenotoxic Activity on Human and Bacterial Cells

Abstract

Hyperforin (HF), a substance that accumulates in the leaves and flowers of Hypericum perforatum L. (St. John’s wort), consists of a phloroglucinol skeleton with lipophilic isoprene chains. HF exhibits several medicinal properties and is mainly used as an antidepressant. So far, the antigenotoxicity of HF has not been investigated at the level of primary genetic damage, gene mutations, and chromosome aberrations, simultaneously. The present work is designed to investigate the potential antigenotoxic effects of HF using three different experimental test systems. The antigenotoxic effect of HF leading to the decrease of primary/transient promutagenic genetic changes was detected by the alkaline comet assay on human lymphocytes. The HF antimutagenic effect leading to the reduction of gene mutations was assessed using the Ames test on the standard Salmonella typhimurium (TA97, TA98, and TA100) bacterial strains, and the anticlastogenic effect of HF leading to the reduction of chromosome aberrations was evaluated by the in vitro mammalian chromosome aberration test on the human tumor cell line HepG2 and the non-carcinogenic cell line VH10. Our findings provided evidence that HF showed antigenotoxic effects towards oxidative mutagen zeocin in the comet assay and diagnostic mutagen (4-nitroquinoline-1-oxide) in the Ames test. Moreover, HF exhibited an anticlastogenic effect towards benzo(a)pyrene and cisplatin in the chromosome aberration test.

Anti-Tumor Activity of Hypericum perforatum L. and Hyperforin through Modulation of Inflammatory Signaling, ROS Generation and Proton Dynamics

“…Tumor prevention. Regular use of SJW reduces cancer risk, by preventing the genotoxic effect of carcinogens [ 144 ]. This protective action is essentially based on the ability of HPF to slowdown inflammatory mediators and regulate ROS production and/or pH imbalance, resulting in counteraction of malignant phenotype.…”

“…Mainly due to their inhibitory action on inflammation-generated byproducts, SJW and HPF can also help preventing genotoxic effects. Actually, the anti-genotoxic ability of HPF has been verified by measuring the amount of bacterial gene mutations (Ames’ test), the occurrence of DNA strand breaks in human lymphocytes (comet assay) and the induction of chromosome aberrations in a mammalian cell line [ 144 ]. The results showed that HPF (at a concentration of about 1 µM) displays indeed anti-mutagenic activity as well as DNA protective effect against zeocin-induced single- and double-strand breaks and reduction of chromosome aberrations in human liver cells exposed to benzo[a]pyrene (B[a]P) or cisplatin.…”

“…The results showed that HPF (at a concentration of about 1 µM) displays indeed anti-mutagenic activity as well as DNA protective effect against zeocin-induced single- and double-strand breaks and reduction of chromosome aberrations in human liver cells exposed to benzo[a]pyrene (B[a]P) or cisplatin. This suggests that HPF could de facto contribute to reduce human environmental risk [ 144 ]. The SJW- and HPF-dependent prevention of ROS generation, observed in different in vitro and in vivo inflammatory models [ 123 , 124 , 126 , 127 , 128 , 145 , 146 ], may account for their protective effect against genotoxic insults.…”

“…In particular, the HPF ability to decrease ROS production could be crucial to prevent the genotoxic action of zeocin, that was reported to cause DNA damage in two breast cancer cell lines mainly by increasing intracellular ROS level [ 147 , 148 ]. Furthermore, the aforementioned protonophore action of HPF, by allowing protons to re-enter the cytosol and thus hinder intracellular alkalization, might explain the HPF protective effect on B[a]P-induced carcinogenesis, reported by Imreova et al [ 144 ]. In fact, intracellular alkalization was detected in rat hepatic epithelial F258 cells quickly upon exposure to B[a]P, resulting in alteration of pH dynamics in different cell compartments including mitochondria and affecting mitochondrial function [ 149 ].…”

Polycyclic Polyprenylated Acylphloroglucinol Derivatives from Hypericum acmosepalum

“…Hypericum plants have diverse pharmacological applications as folk medicines due to the diverse chemical constituents [4,5,6]. As a classical natural product from this family, polycyclic polyprenylated acylphloroglucinols (PPAPs) have intriguing chemical structures [7,8,9] and various biological activities, such as anti-neurodegenerative, anti-HIV, tumor inhibitory, antioxidative, antidepressant, and so on [10,11,12,13,14,15].…”