The biological activity of Hypericum extracts should

The biological activity of Hypericum extracts should not be exclusively explained based on the effects of the major compound because it may also include the response to other bioactive compounds present in smaller concentrations. Interaction between compounds (synergistic effect) present in the extracts and also to metabolites formed during the metabolism of phytochemicals that could be more active than the original compound can also not be excluded at this point. In conclusion, Hypericum water extracts possess antigenotoxic properties and protect colon hyPerFUsion™ high-fidelity DNA polymerase from oxidative and alkylating DNA damage also increasing alkylating DNA repair activity. The protective effect could be due, in part, to the presence of high amount of phenolic compounds that showed to be also protective. However, other factors, referred previously, should be attended to in future studies. Consumption of herbal teas produced with Hypericum sp, namely Hypericum perforatum, Hypericum androsaeum, and Hypericum undulatum may contribute to colon cancer prevention.
Conflict of Interest
Acknowledgements Marques F. was supported by the Foundation for Science and Technology (FCT), Portugal, Grant UMINHO/BI/35/2012. This work was supported by FCT by the Project PTDC/AGR-AAM/70418/2006.
Introduction β-methylamino-l-alanine (BMAA) exposure has long been associated with neurodegenerative diseases, particularly on Guam where high rates of amyotrophic lateral sclerosis (ALS) and Parkinson’s disease-like dementia complex (ALS-PDC) have been reported (Reed and Brody, 1975, Bradley and Mash, 2009). Such conditions have been linked to consumption of foodstuffs with high BMAA levels, typically flying foxes and other animals that bioaccumulate BMAA in their tissues as a result of eating cycad seeds (Bradley and Mash, 2009, Cox et al., 2003). The increasing westernisation of the diet on Guam has decreased consumption of these BMAA rich dietary sources and this has been linked to decreases in the incidence of ALS and ALS-PDC on Guam (Plato et al., 2003). These observations are consistent with BMAA being neurotoxic in humans. BMAA is present in cycad seeds through synthesis by symbiotic cyanobacteria. While numerous cyanobacteria species can produce BMAA (Cox et al., 2005), it is currently unclear to what extent humans may be exposed e.g. via cyanobacterial blooms (Faassen, 2014). However, BMAA has been found in the brains of ALS and other patients not only from Guam but also North America and this does suggest a more widespread exposure than initially considered (Murch et al., 2004a, Pablo et al., 2009). In vitro studies have shown that BMAA is toxic to neurons (Chiu et al., 2011, Lobner, 2009). BMAA can react with bicarbonate ions to form a β-carbamate that is a structural analogue of glutamate and hence can bind to various glutamate receptors including the N-methyl-d-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors leading to excitotoxicity. Receptor activation leads to a chain of events that involves increased concentrations of intracellular Na+ and Ca2+ and decreased K+ levels, altered membrane permeability, mitochondrial dysfunction and increased reactive oxygen species (ROS) production, and ultimately leads to cell death (Chiu et al., 2011, Lobner, 2009). BMAA can also act as a substitute for L-serine and be incorporated into human (Dunlop et al., 2013), though not bacterial proteins (van Onselen et al., 2015) nor proteins obtained from the brains of BMAA treated cynomologus monkeys (Spencer et al., 2016). BMAA incorporated into proteins can cause protein misfolding and aggregation (Dunlop et al., 2013) a process often linked to neurodegenerative disease (Rodgers, 2014). Furthermore, protein-bound BMAA may act as a reservoir that releases free BMAA as proteins are degraded (Murch et al., 2004b).