Beneficial effects of naringenin in liver diseases: Molecular mechanisms

World J Gastroenterol. 2018 Apr 28;24(16):1679-1707. doi: 10.3748/wjg.v24.i16.1679.


Liver diseases are caused by different etiological agents, mainly alcohol consumption, viruses, drug intoxication or malnutrition. Frequently, liver diseases are initiated by oxidative stress and inflammation that lead to the excessive production of extracellular matrix (ECM), followed by a progression to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). It has been reported that some natural products display hepatoprotective properties. Naringenin is a flavonoid with antioxidant, antifibrogenic, anti-inflammatory and anticancer properties that is capable of preventing liver damage caused by different agents. The main protective effects of naringenin in liver diseases are the inhibition of oxidative stress, transforming growth factor (TGF-β) pathway and the prevention of the transdifferentiation of hepatic stellate cells (HSC), leading to decreased collagen synthesis. Other effects include the inhibition of the mitogen activated protein kinase (MAPK), toll-like receptor (TLR) and TGF-β non-canonical pathways, the inhibition of which further results in a strong reduction in ECM synthesis and deposition. In addition, naringenin has shown beneficial effects on nonalcoholic fatty liver disease (NAFLD) through the regulation of lipid metabolism, modulating the synthesis and oxidation of lipids and cholesterol. Moreover, naringenin protects from HCC, since it inhibits growth factors such as TGF-β and vascular endothelial growth factor (VEGF), inducing apoptosis and regulating MAPK pathways. Naringenin is safe and acts by targeting multiple proteins. However, it possesses low bioavailability and high intestinal metabolism. In this regard, formulations, such as nanoparticles or liposomes, have been developed to improve naringenin bioavailability. We conclude that naringenin should be considered in the future as an important candidate in the treatment of different liver diseases.

Keywords: CCl4; Cirrhosis; Fibrosis; Flavonoids; Hepatic stellate cells; JNK; Liver; MAPKs; Naringenin; Smads; Transforming growth factor; α-SMA.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / therapeutic use*
  • Anticarcinogenic Agents / adverse effects
  • Anticarcinogenic Agents / pharmacokinetics
  • Anticarcinogenic Agents / therapeutic use*
  • Antioxidants / adverse effects
  • Antioxidants / pharmacokinetics
  • Antioxidants / therapeutic use*
  • Collagen / metabolism
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Flavanones / adverse effects
  • Flavanones / pharmacokinetics
  • Flavanones / therapeutic use*
  • Hepatic Stellate Cells / drug effects
  • Hepatic Stellate Cells / metabolism
  • Hepatic Stellate Cells / pathology
  • Humans
  • Inflammation Mediators / metabolism
  • Lipid Metabolism / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases / diagnosis
  • Liver Diseases / drug therapy*
  • Liver Diseases / etiology
  • Liver Diseases / metabolism
  • Oxidative Stress / drug effects
  • Signal Transduction / drug effects


  • Anti-Inflammatory Agents
  • Anticarcinogenic Agents
  • Antioxidants
  • Flavanones
  • Inflammation Mediators
  • Collagen
  • naringenin