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

Area of Science:

• Nutrigenomics and Epigenetics
• Molecular Biology
• Biochemistry

Background:

• Nutrigenomics explores diet-genome interactions.
• Epigenetic regulation, particularly histone deacetylase (HDAC) inhibition, is implicated in chronic disease.
• Limited research exists on screening bioactive compounds as epigenetic modifiers.

Purpose of the Study:

• To screen a library of natural compounds for histone deacetylase (HDAC) inhibitory activity.
• To identify bioactive compounds that can modify the epigenome.
• To lay the groundwork for developing novel epigenetic therapies for chronic diseases.

Main Methods:

• Screened 131 natural compounds using class-specific HDAC substrates in bovine cardiac tissue.
• Tested identified inhibitors against recombinant HDAC proteins to confirm isoform-specific activity.
• Assessed the effect of HDAC inhibitors on lysine acetylation in H9c2 cardiac myoblasts via immunoblot.

Main Results:

• Identified 18 natural compounds that inhibit HDAC activity.
• Confirmed that these compounds inhibit specific HDAC isoforms.
• Demonstrated that treatment with these compounds increases lysine acetylation in cardiac myoblasts.

Conclusions:

• This study represents a significant first step in identifying novel bioactive HDAC inhibitors from natural sources.
• The identified compounds show potential as epigenetic regulators.
• Further research into these compounds could lead to new strategies for ameliorating chronic diseases.