Abstract
The Mediterranean plant Silybum marianum L., commonly known as milk thistle, has been used for centuries to treat liver disorders. The flavonolignan silibinin represents a natural antioxidant and the main bioactive ingredient of silymarin (silybin), a standard extract of its seeds. Mitochondrial dysfunction and the associated generation of reactive oxygen/nitrogen species (ROS/RNS) are involved in the development of chronic liver and age-related neurodegenerative diseases. Silibinin A (SIL A) is one of two diastereomers found in silymarin and was used to evaluate the effects of silymarin on mitochondrial parameters including mitochondrial membrane potential and ATP production with and without sodium nitroprusside- (SNP-) induced nitrosative stress, oxidative phosphorylation, and citrate synthase activity in HepG2 and PC12 cells. Both cell lines were influenced by SIL A, but at different concentrations. SIL A significantly weakened nitrosative stress in both cell lines. Low concentrations not only maintained protective properties but also increased basal mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) levels. However, these effects could not be associated with oxidative phosphorylation. On the other side, high concentrations of SIL A significantly decreased MMP and ATP levels. Although SIL A did not provide a general improvement of the mitochondrial function, our findings show that SIL A protects against SNP-induced nitrosative stress at the level of mitochondria making it potentially beneficial against neurological disorders.
Highlights
The Mediterranean plant Silybum marianum L. (Gaertn.; (Compositae)), commonly known as milk thistle, has been used for centuries to treat disorders of the liver
Our data showed that mitochondrial parameters measured in hepatic HepG2 and in undifferentiated PC12 cells significantly differ from each other
In hepatic HepG2 cells, Silibinin A (SIL A) enhanced the activity of respiratory complexes and subsequently may be responsible for an increase in the production of adenosine triphosphate (ATP)
Summary
The Mediterranean plant Silybum marianum L. (Gaertn.; (Compositae)), commonly known as milk thistle, has been used for centuries to treat disorders of the liver. HepG2 cells are widely used to study the mechanisms of drug actions, and it has already been reported that SIL A reduced oxidative stress in HepG2 cells [10]. SIL A prevents dopaminergic neuronal loss in cellular and animal models of PD, and it was suggested that its neuroprotective effect might be mediated by the stabilization of the mitochondrial membrane potential (MMP) [14]. In PC12 cells, silybin and SIL A were found to attenuate oxidative and nitrosative stress [15, 16]. In this work, we evaluated the effects of SIL A on oxidative phosphorylation, MMP, ATP levels, and citrate synthase activity in PC12 cells and HepG2 cells, both subjected to and without SNP-induced nitrosative stress
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