Fibrosis process in the liver is a clinical condition established in response to chronic lesions and may be reversible in many situations. In this process, hepatic stellate cells (HSCs) activate and produce extracellular matrix compounds. During fibrosis, the lipid metabolism is also altered and contributes to the transdifferentiation of the HSCs. Thus, controlling lipid metabolism in HSCs is suggested as a method to control or reverse the fibrotic condition. In the search for therapies that modulate lipid metabolism and treat liver diseases, silymarin has been identified as a relevant natural compound to treat liver pathologies. The present study aimed to evaluate the cellular and molecular effects of silymarin in the transdifferentiation process of HSCs (LX-2) from activated phenotype to a more quiesced-like cells , also focusing on understanding the modulatory effects of silymarin on lipid metabolism of HSCs. In our analyses, 100 µM of silymarin reduced the synthesis of actin filaments in activated cells, the synthesis of the protein level of α-SMA, and other pro-fibrotic factors such as CTGF and PFGF. The concentration of 150 µM silymarin did not reverse the activation aspects of LX-2 cells. However, both evaluated concentrations of the natural compound protected the cells from the negative effects of dimethyl sulfoxide (DMSO). Furthermore, we evaluated lipid-related molecules correlated to the transdifferentiation process of LX-2, and 100 µM of silymarin demonstrated to control molecules associated with lipid metabolism such as FASN, MLYCD, ACSL4, CPTs, among others. In contrast, cellular incubation with 150 µM of silymarin increased the synthesis of long-chain fatty acids and triglycerides, regarding the higher presence of DMSO (v/v) in the solvent. In conclusion, silymarin acts as a hepatoprotective agent and modulates the pro-fibrogenic stimuli of LX-2 cells, whose effects depend on stress levels in the cellular environment.

中文翻译：

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水飞蓟素对LX-2细胞转分化过程的细胞和分子作用及其与脂质代谢的关系。

肝脏中的纤维化过程是针对慢性病变而建立的临床状况，在许多情况下可能是可逆的。在这个过程中，肝星状细胞（HSC）活化并产生细胞外基质化合物。在纤维化过程中，脂质代谢也会发生改变，并有助于HSC的转分化。因此，建议控制HSC中的脂质代谢作为控制或逆转纤维化病状的方法。在寻找调节脂质代谢和治疗肝脏疾病的疗法中，水飞蓟素已被确定为治疗肝脏疾病的相关天然化合物。本研究旨在评估水飞蓟素在HSC（LX-2）从活化表型到更静止的细胞的转分化过程中的细胞和分子作用，还着重于了解水飞蓟素对HSCs脂质代谢的调节作用。在我们的分析中，水飞蓟素100 µM减少了活化细胞中肌动蛋白丝的合成，α-SMA蛋白质水平的合成以及其他促纤维化因子（例如CTGF和PFGF）的合成。150 µM水飞蓟素的浓度不会逆转LX-2细胞的激活状态。但是，两种评估浓度的天然化合物均可保护细胞免受二甲基亚砜（DMSO）的不利影响。此外，我们评估了与LX-2转分化过程相关的脂质相关分子，并证明了100 µM水飞蓟素可控制与脂质代谢相关的分子，例如FASN，MLYCD，ACSL4，CPT等。相反，考虑到溶剂中DMSO（v / v）的含量较高，用150 µM水飞蓟素进行细胞温育可增加长链脂肪酸和甘油三酸酯的合成。总之，水飞蓟素可作为肝保护剂并调节LX-2细胞的促纤维化刺激作用，其作用取决于细胞环境中的应激水平。