Fondazione Italiana Fegato, ONLUS, AREA Science Park Basovizza SS 14 km 163.5, 34149 Trieste, Italy.
Molecules. 2019 Apr 2;24(7):1280. doi: 10.3390/molecules24071280.
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.
水飞蓟宾被提议用于治疗非酒精性脂肪性肝炎（NASH）。在这项研究中，我们评估了水飞蓟宾在一个成熟的体外 NASH 早期共培养模型中的作用。LX2 和 Huh7 细胞暴露于游离脂肪酸（FFA）和水飞蓟宾的单一或共培养（SCC）中。在 24、96 和 144 小时时测定细胞活力、LX2 激活、胶原沉积、金属蛋白酶 2 和 9（MMP2-9）活性和 ROS 生成。FFA 的暴露如通过细胞活力的增加和胶原生物合成的上调所示诱导 LX2 的激活。有趣的是，虽然水飞蓟宾的共同处理并没有影响 LX2 中的胶原产生，但在 SCC 中观察到显著减少。MMP2-9 活性在 FFA 处理的 Huh7 和 SCC 中降低，并且与水飞蓟宾的共同处理诱导剂量依赖性增加，而在 LX2 中没有观察到。水飞蓟宾还通过减少所有细胞系统中 FFA 诱导的 ROS 产生表现出抗氧化特性。基于这些数据，水飞蓟宾通过减少 LX2 的增殖和 ROS 的产生发挥其有益作用。此外，肝细胞中 MMP2-9 的调节代表了这种 NASH 体外模型中胶原净减少的驱动机制，突出了肝细胞相互作用在 NASH 发展和解决中的重要性。
