Ellagic acid: Pharmacological activities and molecular mechanisms involved in liver protection.
Traditional drugs or therapies rarely have effects on regression of chronic liver diseases, which result in many cases from sustained oxidative stress. In recent years, ellagic acid (EA) has gained attention due to its multiple biological activities and several molecular targets. This is the first review focused on the pharmacological properties and on the molecular mechanisms activated by EA in terms of liver protection. EA possesses antioxidant, antihepatotoxic, antisteatosic, anticholestatic, antifibrogenic, antihepatocarcinogenic and antiviral properties that improves the hepatic architectural and functions against toxic and pathological conditions. The molecular mechanisms that EA activates include the scavenging of free radicals, regulation of phase I and II enzymes, modulation of proinflammatory and profibrotic cytokines synthesis, the regulation of biochemical pathways involved in the synthesis and degradation of lipids as well as the maintenance of essential trace elements levels. EA also inhibits hepatic stellate cells and mast cells activation, the proliferation of transformed cells, as well as viral replication by increasing antioxidant response, induction of apoptosis, downregulation of genes involved in cell cycle and angiogenesis, and stimulation of cellular immune response. Despite the enormous therapeutic potential of EA as an innovative pharmacological strategy, the number of phase I and II trials in patients is scarce, precluding its clinical application. In these sense, the use of new delivery systems that enhances EA bioavailability would improve the results already obtained. Also it remains to be determined if treatment with urolithins instead of EA would represent a better strategy in hepatic disease treatment.
Department of Cardiovascular Biomedicine, National Institute of Cardiology "Ignacio Chávez", Juan Badiano No. 1, Section XVI, 14080, D.F., Mexico. Electronic address: wramsesgarcia@gmail.com.
Wylly Ramsés
WR
García-Niño
Department of Cardiovascular Biomedicine, National Institute of Cardiology "Ignacio Chávez", Juan Badiano No. 1, Section XVI, 14080, D.F., Mexico.
Cecilia
C
Zazueta
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000517:prevention & control*; D002779:Cholestasis / Q000517:prevention & control; D004610:Ellagic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D005234:Fatty Liver / Q000517:prevention & control; D055166:Hepatic Stellate Cells / Q000187:drug effects; D006518:Hepatitis Viruses / Q000187:drug effects; D006801:Humans; D008113:Liver Neoplasms / Q000517:prevention & control; D020011:Protective Agents / Q000494:pharmacology*
D000998:Antiviral Agents; D020011:Protective Agents; D004610:Ellagic Acid
Alcohol (Pubchem CID: 702); Carbon tetrachloride (Pubchem CID: 5943); Cisplatin (Pubchem CID: 2767); Cyclosporine A (Pubchem CID: 5284373); Ellagic acid; Ellagic acid (PubChem CID: 5281855); Isoniazid (Pubchem CID: 3767); Lipopolysacharide (Pubchem CID: 11970143); Liver protection; Molecular targets; Paracetamol (Pubchem CID: 1983); Pharmacological activities; Rifampicin (Pubchem CID: 5381226); d-Galactosamine (Pubchem CID: 24154)