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Issue 3-4, 2011
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Antiproliferative mechanisms of quercetin in rat activated hepatic stellate cells

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Abstract

Quercetin, rich in fruits and vegetables, has been used as a nutritional supplement because of its anti-inflammatory and antioxidative properties. Its positive effects on anti-hepatic fibrosis have also been suggested. However the anti-hepatofibrotic mechanisms upon which quercetin acts have yet to be well characterized. In the present study, we investigated the anti-proliferative effect of quercetin on activated hepatic stellate cells (aHSCs), the central role of hepatofibrosis, and evaluated the proteins involved in growth inhibition by a 2D gel electrophoretic analysis. Activated HSCs were isolated from Sprague Dawley rats and were spontaneously activated in vitro. Quercetin restrained the proliferation of aHSCs rather than quiescent HSCs and heptotcytes by inducing a G1 arrest as examined by cell cycle analysis and evidenced by increased levels of p53, p21CIP1/WAF1, as well as p27KIP1, and decreased abundance of cyclins (D1, D2, A, E). An apoptosis through extrinsic pathway as demonstrated by elevated expression of Fas/Fas ligand (FasL), annexin V labeling, chromatin condensation, sub-G1 fraction (7.39%), caspase-3 activity, was also observed. The 2D electrophoresis analysis revealed that quercetin negatively regulated protein molecules associated with metabolism (α-enolase, phosphoglycerate kinase), survival, cytokinesis (tubulin), and protein folding (protein disulfide isomerase A3) leading to cell growth retardation. Furthermore, quercetin might restrain HSC activation through reducing the levels of inflammatory cytokines (CXCL10, Midkine). Taken together, quercetin exerted diverse mechanisms to inhibit the growth of aHSCs. Proper consumption of quercetin could be beneficial to control the progression of heptofibrosis.

Graphical abstract: Antiproliferative mechanisms of quercetin in rat activated hepatic stellate cells

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Article information


Submitted
26 Oct 2010
Accepted
02 Mar 2011
First published
21 Mar 2011

Food Funct., 2011,2, 204-212
Article type
Paper

Antiproliferative mechanisms of quercetin in rat activated hepatic stellate cells

L. Wu, I. Lu, C. Chung, H. Wu and Y. Liu, Food Funct., 2011, 2, 204
DOI: 10.1039/C0FO00158A

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