Antifibrotic Mechanism of Pinocembrin: Impact on Oxidative Stress, Inflammation and TGF-β /Smad Inhibition in Rats.

Abstract

INTRODUCTION:

The present study aimed to elucidate the potential antifibrotic effects of pinocembrin (PIN), a flavanone found abundantly in honey and propolis, by studying its effect on different oxidative stress, inflammatory and fibrosis markers in an experimental model of CCl4-induced liver fibrosis.

MATERIAL AND METHODS:

PIN (20 mg/kg) was given orally 3 times/week for 6 consecutive weeks alternating with CCl4 (0.5 mL/kg, 1:1 mixture with corn oil, i. p.) twice weekly. Different hepatotoxicity indices, oxidative stress, inflammatory and liver fibrosis markers were assessed.

RESULTS:

PIN significantly restored liver transaminases and total cholesterol to normal levels. Also, PIN ameliorated oxidative stress injury evoked by CCl4 as evidenced by inhibition of reduced glutathione depletion and lipid peroxidation as well as elevation of antioxidant enzyme superoxide dismutase (SOD). Further, PIN upregulated the nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), thereby inducing the expression and activity of the cytoprotective enzyme hemeoxygenase-1 (HO-1). Moreover, PIN alleviated pro-inflammatory cytokines such as TNF-α via inhibiting nuclear factor-κB (NF-κB) activation. As markers of fibrosis, collagen and α-SMA expression increased markedly in the CCl4 group and PIN prevented these alterations. In addition, PIN down-regulated TGFβ1 and p-Smad2/3, thereby inhibiting TGFβ1/Smad signaling pathway.

CONCLUSION:

These results suggest that PIN possess potent antifibrotic effects that can be explained on its antioxidant properties. It ameliorates oxidative stress and inflammation during induction of fibrogenesis via its ability to augment celular antioxidant defenses, activating Nrf2-mediated HO-1 expression and modulating NF-κB and TGF-β1/Smad signaling pathway.

• Authors: Marwa M Said, Samar S Azab, Noha M Saeed, Ebtehal El-Demerdash
• Journal: Annals of hepatology (Ann Hepatol) Vol. 17 Issue 2 Pg. 307-317 (Mar 01 2018) ISSN: 1665-2681 [Print] Mexico
• PMID: 29469035 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Biomarkers
• Flavanones
• Inflammation Mediators
• NF-E2-Related Factor 2
• NF-kappa B
• Nfe2l2 protein, rat
• Smad2 Protein
• Smad2 protein, rat
• Smad3 Protein
• Smad3 protein, rat
• Tgfb1 protein, rat
• Transforming Growth Factor beta1
• pinocembrin
• Carbon Tetrachloride
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Biomarkers (metabolism)
• Carbon Tetrachloride
• Chemical and Drug Induced Liver Injury (etiology, metabolism, pathology, prevention & control)
• Flavanones (pharmacology)
• Heme Oxygenase (Decyclizing) (metabolism)
• Inflammation Mediators (metabolism)
• Lipid Peroxidation (drug effects)
• Liver (drug effects, metabolism, pathology)
• Liver Cirrhosis, Experimental (chemically induced, metabolism, pathology, prevention & control)
• Male
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)
• Phosphorylation
• Rats, Wistar
• Signal Transduction (drug effects)
• Smad2 Protein (metabolism)
• Smad3 Protein (metabolism)
• Transforming Growth Factor beta1 (metabolism)