Combination of pomegranate extract and curcumin ameliorates thioacetamide-induced liver fibrosis in rats: impact on TGF-β/Smad3 and NF-κB signaling pathways

Abstract

Protection against liver injury and its consequences is considered an essential issue to minimize the number of annual deaths caused by liver diseases. The present study was designed to evaluate the potential role of pomegranate extract (PE) and/or curcumin in the regression of thioacetamide (TAA)-induced liver fibrosis, focusing on their modulatory effects on Nrf2/HO-1, NF-κB, and TGF-β/Smad3 signaling pathways. Liver fibrosis was induced in male Wistar rats by intraperitoneal injection of TAA (100 mg/kg) three times a week, for 8 weeks. To assess the protective effects of PE and/or curcumin against TAA-induced liver fibrosis, rats were treated on a daily basis with oral doses of PE (200 mg/kg) and/or curcumin (200 mg/kg) for 8 weeks. The results indicated that PE and/or curcumin attenuated TAA-induced liver fibrogenesis, as evidenced by a significant improvement in the liver function tests (AST, ALT, ALP, and albumin), oxidative stress biomarkers (MDA, SOD, and GSH), and inflammatory biomarkers (NF-ĸB, TNF-α, IL-1β, iNOS, TGF-β, and MPO), compared to TAA group. Moreover, treatment with PE and/or curcumin exerted a significant upregulation of Nrf2/HO-1 gene expressions along with significant downregulation of NF-ĸB, TGF-β, and phospho-Smad3 protein expressions, as well as α-SMA and collagen-1 gene expressions. The histopathological examination has corroborated these findings. In conclusion, hepatoprotective activities of PE and/or curcumin could be linked to their abilities to modulate Nrf2/HO-1, NF-κB, and TGF-β/Smad3 signaling pathways. It is worth noting that the combination of PE and curcumin exerted superior hepatoprotective effects against TAA-induced liver fibrosis, as compared to monotherapy.

Keywords:

• Thioacetamide
• curcumin
• pomegranate extract
• liver fibrosis
• TGF-β/Smad3

Acknowledgments

The English editing for the whole manuscript has been appreciatively done by Dr. Mohammed Salah, Head of Translation Department & Academic Supervisor of Study Programs, Center for Foreign Language and Professional Translation (CLT), Cairo University. In addition, the English language of the manuscript was re-checked and re-edited by Prof. Elham Abdelfattah, Chief Executive Officer (CEO) of ISO Accredited Translation Firm.

Ethical approval

The study was approved by the Ethics Committee for Animal Experimentation at Faculty of Pharmacy, Cairo University (Permit number: PT 1920), and complied with the Guide for Care and Use of Laboratory Animals published by the US National Institutes of Health (NIH publication No. 85–23, revised 2011).

Author contribution

AMH Gowifel and MG Khalil conceived and designed the study, performed experiments, prepared figures, analyzed & interpreted data, and drafted the manuscript. MM Safar interpreted data, edited, and revised the manuscript. KA Ahmed examined histopathological specimens and interpreted its data. MM Salama performed phytochemical analysis and interpreted its data. SA Nada and SA Kenawy conceived and designed the study. The final manuscript was reviewed, and approved by all authors.

Disclosure statement

No potential conflict of interest was reported by the author(s).