| Autor: |
Balta C; 'Aurel Ardelean' Institute of Life Sciences, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania., Herman H; 'Aurel Ardelean' Institute of Life Sciences, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania., Ciceu A; 'Aurel Ardelean' Institute of Life Sciences, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania., Mladin B; 'Aurel Ardelean' Institute of Life Sciences, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania., Rosu M; 'Aurel Ardelean' Institute of Life Sciences, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania., Sasu A; 'Aurel Ardelean' Institute of Life Sciences, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania., Peteu VE; Victor Babes National Institute of Pathology, 050096 Bucharest, Romania., Voicu SN; Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania., Balas M; Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania., Gherghiceanu M; Victor Babes National Institute of Pathology, 050096 Bucharest, Romania.; Department of Cellular and Molecular Biology and Histology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania., Dinischiotu A; Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania., Olah NK; Faculty of Pharmacy, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania., Hermenean A; 'Aurel Ardelean' Institute of Life Sciences, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania.; Faculty of Medicine, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania. |
| Abstrakt: |
In this study, we aimed to explore the hepatoprotective effects of the gemmotherapy bud extract of Corylus avellana in a model of liver fibrosis on diabetic mice. An evaluation of total flavonoids and polyphenols contents and LC/MS analyses were performed. Experimental fibrosis was induced with CCl 4 (2 mL/kg by i.p. injections twice a week for 7 weeks) in streptozotocin-induced diabetic mice. Our results showed a content of 6-7% flavonoids, while hyperoside and chlorogenic acids were highlighted in the bud extract. Toxic administration of CCl 4 increased oxidative stress, mRNA expression of the transforming growth factor-β1 ( TGF-β1 ) and Smad 2/3 , and reduced Smad 7 expression. Furthermore, up-regulation of α-smooth muscle actin ( α-SMA ) revealed an activation of hepatic stellate cells (HSCs), while collagen I ( Col I ) up-regulation and matrix metalloproteinases ( MMPs ) unbalance led to an altered extracellular matrix enriched in collagen, confirmed as well by a trichrome stain and electron microscopy analysis. Treatment with gemmotherapy extract significantly restored the liver architecture and the antioxidant balance, and significantly decreased collagen deposits in the liver and improved the liver function. Our results suggest that Corylus avellana gemmotherapy extract may have anti-fibrotic effects and could be useful in the prevention and treatment of liver fibrosis. The hepatoprotective mechanism is based on HSC inhibition, a reduction in oxidative stress and liver damage, a downregulation of the TGF-β1/Smad signaling pathway and a MMPs/TIMP rebalance. |
