Anti-Fibrotic Effects of Valproic Acid: Role of HDAC Inhibition and Associated Mechanisms

Abstract

Tissue injuries and pathological insults produce oxidative stress, genetic and epigenetic alterations, which lead to an imbalance between pro- and anti-fibrotic molecules, and subsequent accumulation of extracellular matrix, thereby fibrosis. Various molecular pathways play a critical role in fibroblasts activation, which promotes the extracellular matrix production and accumulation. Recent reports highlighted that histone deacetylases (HDACs) are upregulated in various fibrotic disorders and play a central role in fibrosis, while HDAC inhibitors exert antifibrotic effects. Valproic acid is a first-line anti-epileptic drug and a proven HDAC inhibitor. This review provides the current research and novel insights on antifibrotic effects of valproic acid in various fibrotic conditions with an emphasis on the possible strategies for treatment of fibrosis.

Keywords::

• epigenetics
• fibrosis
• HDAC inhibitors
• histone acetylation
• post-translational modifications
• valproic acid

Acknowledgements

The authors would like to thank C Gupta (Research Scientist, ResearchDx Irvine, CA, USA), S Kumar (Research Scientist, Wockhardt Research Centre, Aurangabad, India), K Prahlad Maremanda and V Rao Amara (Senior Research Fellows of department pharmacology and toxicology, NIPER S.A.S. Nagar, Punjab, India) for English language/grammatical corrections in the present manuscript.

Financial & competing interests disclosure

This work has been funded by National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali, India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work has been funded by National Institute of Pharmaceutical Education and Research, S.A.S. Nagar, Mohali, India. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.