Journal
MOLECULAR AND CELLULAR BIOCHEMISTRY
Volume 468, Issue 1-2, Pages 129-142Publisher
SPRINGER
DOI: 10.1007/s11010-020-03717-7
Keywords
Hepatic stellate cell; Lipid metabolism; Liver fibrosis; Natural compound
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Funding
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo [FAPESP-2013/21186-7, 2016/23509-4, 2018/05286-3]
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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 mu M of silymarin reduced the synthesis of actin filaments in activated cells, the synthesis of the protein level of alpha-SMA, and other pro-fibrotic factors such as CTGF and PFGF. The concentration of 150 mu M 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 mu M of silymarin demonstrated to control molecules associated with lipid metabolism such as FASN, MLYCD, ACSL4, CPTs, among others. In contrast, cellular incubation with 150 mu M 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.
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