Targeting the epigenome: Screening bioactive compounds that regulate histone deacetylase activity

Abstract

Scope Nutrigenomics is a rapidly expanding field that elucidates the link between diet-genome interactions. Recent evidence demonstrates that regulation of the epigenome, and in particular inhibition of HDACs, impact pathogenetic mechanisms involved in chronic disease. Few studies, to date, have screened libraries of bioactive compounds that act as epigenetic modifiers. This study screened a library of 131 natural compounds to determine bioactive compounds that inhibit Zn-dependent HDAC activity. Methods and results Using class-specific HDAC substrates, we screened 131 natural compounds for HDAC activity in bovine cardiac tissue. From this screen, we identified 18 bioactive compound HDAC inhibitors. Using our class-specific HDAC substrates, we next screened these 18 bioactive compounds against recombinant HDAC proteins. Consistent with inhibition of HDAC activity, these compounds were capable of inhibiting activity of individual HDAC isoforms. Lastly, we report that treatment of H9c2 cardiac myoblasts with bioactive HDAC inhibitors was sufficient to increase lysine acetylation as assessed via immunoblot. Conclusion This study provided the first step in identifying multiple bioactive compound HDAC inhibitors. Taken together, this report sets the stage for future exploration of these bioactive compounds as epigenetic regulators to potentially ameliorate chronic disease.

Natural Products and Chemical Biology Tools: Alternatives to Target Epigenetic Mechanisms in Cancers

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“…Apigenin is abundantly present in common fruits and vegetables such as grapefruit, parsley, chamomile and wheat sprouts, and has been shown to be an in vitro HDAC inhibitor, with an IC 50 value of 27 μM for class I HDAC and no observed inhibition of class IIa and IIb . In a 2012 study, Pandey et al .…”

“…Godoy et al . measured IC 50 values ranging from 17 and 18 μM for inhibition of class I, IIa and IIb HDAC, among the lowest for flavonoid derivatives . In 2011, Attoub et al .…”

Therapeutic Potential for Natural Product HDAC Inhibitors in Heart Failure

“…Recently, we screened several isolated bioactive compounds (131 compounds) found in plants, herbs, and food stuffs as potential inhibitors of HDAC activity in the bovine heart [60]. HDACs were specific to the non-sirtuin, zinc-dependent HDACs-class I, IIa, and IIb.…”

Fermented Butyrate of Aloe vera and A. arborescens by Endophytic Bacteria: Its Prophylactic Action on Brain Insulin Resistance

“…Recent evidence demonstrates that regulation of the epigenome, and in particular inhibition of HDACs, impact pathogenic mechanisms involved in chronic disease. Godoy et al [8] investigated a library of 131 natural compounds to determine bioactive compounds that inhibit Zn-dependent HDAC activity.…”