Phytochemical Profiling and Anti-Fibrotic Activities of the Gemmotherapy Bud Extract of <i>Corylus avellana</i> in a Model of Liver Fibrosis on Diabetic Mice
Cornel Balta,
Hildegard Herman,
Alina Ciceu,
Bianca Mladin,
Marcel Rosu,
Alciona Sasu,
Victor Eduard Peteu,
Sorina Nicoleta Voicu,
Mihaela Balas,
Mihaela Gherghiceanu,
Anca Dinischiotu,
Neli Kinga Olah,
Anca Hermenean
Affiliations
Cornel Balta
“Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania
Hildegard Herman
“Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania
Alina Ciceu
“Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania
Bianca Mladin
“Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania
Marcel Rosu
“Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania
Alciona Sasu
“Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania
Victor Eduard Peteu
Victor Babes National Institute of Pathology, 050096 Bucharest, Romania
Sorina Nicoleta Voicu
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania
Mihaela Balas
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania
Mihaela Gherghiceanu
Victor Babes National Institute of Pathology, 050096 Bucharest, Romania
Anca Dinischiotu
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania
Neli Kinga Olah
Faculty of Pharmacy, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania
Anca Hermenean
“Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University, 86 Rebreanu, 310414 Arad, Romania
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 CCl4 (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 CCl4 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.
