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Open AccessArticle

Silybin Modulates Collagen Turnover in an In Vitro Model of NASH

Fondazione Italiana Fegato, ONLUS, AREA Science Park Basovizza SS 14 km 163.5, 34149 Trieste, Italy
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Academic Editor: Dominique Delmas
Molecules 2019, 24(7), 1280; https://doi.org/10.3390/molecules24071280
Received: 1 March 2019 / Revised: 21 March 2019 / Accepted: 29 March 2019 / Published: 2 April 2019
(This article belongs to the Special Issue Silymarin and Derivatives: From Biosynthesis to Health Benefits)
Silybin has been proposed as a treatment for nonalcoholic steatohepatitis (NASH). In this study, we assessed the effect of Silybin in a well-established in vitro coculture model of early-stage NASH. LX2 and Huh7 cells were exposed to free fatty acid (FFA) and Silybin as mono- or coculture (SCC). Cell viability, LX2 activation, collagen deposition, metalloproteinase 2 and 9 (MMP2-9) activity, and ROS generation were determined at 24, 96, and 144 h. Exposure to FFA induced the activation of LX2 as shown by the increase in cell viability and upregulation of collagen biosynthesis. Interestingly, while cotreatment with Silybin did not affect collagen production in LX2, a significant reduction was observed in SCC. MMP2-9 activity was reduced in FFA-treated Huh7 and SCC and cotreatment with Silybin induced a dose-dependent increase, while no effect was observed in LX2. Silybin also showed antioxidant properties by reducing the FFA-induced production of ROS in all the cell systems. Based on these data, Silybin exerts its beneficial effects by reducing LX2 proliferation and ROS generation. Moreover, MMP2-9 modulation in hepatocytes represents the driving mechanism for the net reduction of collagen in this NASH in vitro model, highlighting the importance of hepatic cells interplay in NASH development and resolution. View Full-Text
Keywords: NAFLD; NASH; Silybin; fibrogenesis; coculture model; hepatic stellate cells NAFLD; NASH; Silybin; fibrogenesis; coculture model; hepatic stellate cells
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MDPI and ACS Style

Anfuso, B.; Giraudi, P.J.; Tiribelli, C.; Rosso, N. Silybin Modulates Collagen Turnover in an In Vitro Model of NASH. Molecules 2019, 24, 1280.

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