Berberis vulgaris extract/β-cyclodextrin complex increases protection of hepatic cells via suppression of apoptosis and lipogenesis pathways

Ivan,Alexandra; Herman,Hildegard; Balta,Cornel; Hadaruga,Daniel  I.; Mihali,Ciprian‑Valentin; Ardelean,Aurel; Hermenean,Anca

doi:10.3892/etm.2017.4240

Berberis vulgaris extract/β-cyclodextrin complex increases protection of hepatic cells via suppression of apoptosis and lipogenesis pathways

Authors:
- Alexandra Ivan
- Hildegard Herman
- Cornel Balta
- Daniel I. Hadaruga
- Ciprian‑Valentin Mihali
- Aurel Ardelean
- Anca Hermenean
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Affiliations: Department of Experimental and Applied Biology, Institute of Life Sciences, Vasile Goldis Western University of Arad, 310414 Arad, Romania, Department of Applied Chemistry and Organic‑Natural Compounds Engineering, Faculty of Industrial Chemistry and Environmental Engineering, Politehnica University of Timişoara, 300006 Timişoara, Romania
Published online on: March 20, 2017 https://doi.org/10.3892/etm.2017.4240
Pages: 2143-2150
Copyright: © Ivan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Berberis vulgaris (Bv) is well known worldwide for its healing properties. However, limited information is available concerning its mechanism of action and the increased hepatoprotective activity of formulated extracts. This study evaluated the protective effect of Bv bark extract against CCl4‑induced cytotoxicity in Huh7 cells, as well whether β-cyclodextrin complexation of the extract resulted in increased hepatoprotective effects. Huh7 cells were incubated for 48 h with 5, 7.5 and 10 µg/ml of unformulated or formulated Bv extract alone and in co‑treatment with CCl4. The effects on Huh7 cell growth and apoptosis were evaluated by MTT assay, caspase‑3/7 activity and caspase-3 expression, whereas fatty acid changes were investigated by Oil red O staining and the detection of peroxisome proliferator-activated receptor-γ (PPARγ) expression using immunofluorescence. Ultrastructural alterations were observed by electron microscopy. The MTT assay showed that co‑exposure to CCl4 and 7.5 µg/ml formulated extract led to a 1.25‑fold increase in cell viability compared with the non‑formulated extract. Caspase‑3/7 activity decreased by 50% and 70% following co-treatment with unformulated or formulated extract, compared with that in cells treated with CCl4 alone. Furthermore, hepatocyte ultrastructure was protected from CCl4‑induced injury in the two co‑treated groups, intracytoplasmic lipid accumulation decreased significantly and PPARγ expression was restored, in comparison with CCl4-treated cells alone. Formulated and unformulated extracts were efficient against the anti-proliferative and pro‑apoptotic actions of CCl4 through suppression of CCl4‑induced caspase‑3 activation and lipid accumulation. The protective effect of the formulated extract was more pronounced than that of the unformulated one, which may be due to its increased solubility.

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