Natural Dibenzo-α-Pyrones: Friends or Foes?

Abstract

Natural dibenzo-α-pyrones (DAPs) can be viewed from two opposite angles. From one angle, the gastrointestinal metabolites urolithins are regarded as beneficial, while from the other, the emerging mycotoxin alternariol and related fungal metabolites are evaluated critically with regards to potential hazardous effects. Thus, the important question is: can the structural characteristics of DAP subgroups be held responsible for distinct bioactivity patterns? If not, certain toxicological and/or pharmacological aspects of natural DAPs might yet await elucidation. Thus, this review focuses on comparing published data on the two groups of natural DAPs regarding both adverse and beneficial effects on human health. Literature on genotoxic, estrogenic, endocrine-disruptive effects, as well as on the induction of the cellular anti-oxidative defense system, anti-inflammatory properties, the inhibition of kinases, the activation of mitophagy and the induction of autophagy, is gathered and critically reviewed. Indeed, comparing published data suggests similar bioactivity profiles of alternariol and urolithin A. Thus, the current stratification into hazardous Alternaria toxins and healthy urolithins seems debatable. An extrapolation of bioactivities to the other DAP sub-class could serve as a promising base for further research. Conclusively, urolithins should be further evaluated toward high-dose toxicity, while alternariol derivatives could be promising chemicals for the development of therapeutics.

Keywords: DNA damage; bioactives; chemoprevention; emerging contaminants; estrogenicity; functional nutrition; microbiome; mycotoxins; neuroprotection; urolithins.

Figure 1

Chemical structures of the basic DAP scaffold (A), as well as two signature representatives of natural DAP derivatives: the bacterial polyphenol metabolite urolithin A (B) and the Alternaria mycotoxin alternariol (C). The hydroxy group at C1 (marked green) is a common feature of most natural DAPs. Methylation of C5, as well as hydroxylation of C11 (marked red), are common in biosynthesized DAPs but are not featured in ellagitannin biodegradation products.