The Therapeutic Effect of Silymarin and Silibinin on Depression and Anxiety Disorders and Possible Mechanism in the Brain: A Systematic Review

Background: Depression and anxiety are the most common mental disorders worldwide. Objective: We aimed to review silymarin and silibinin effects and underlying mechanisms in the central nervous system (CNS) for depression and anxiety treatment. Methods: The research protocol was prepared based on following the PRISMA statement. An extensive search was done in essential databases such as PubMed, Cochrane Library, Web of Science (ISI), Embase, and Scopus. Considering the study inclusion and exclusion criteria, 17 studies were finally included. The desired information was extracted from the studies and recorded in Excel, and the consequences and mechanisms were reviewed. Results: Silymarin and silibinin upregulated brain-derived neurotrophic factor (BDNF) and improved neural stem cells (NSCs) proliferation in the cortex and hippocampus. They also increased neurochemical serotonin (5-HT), dopamine (DA), and norepinephrine (NE) levels. Silymarin and silibinin reduced malondialdehyde (MDA) formation and increased glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT) activities. In addition, silymarin and silibinin reduced interleukin (IL)-6, IL-1β, and IL-12β, reducing tumor necrosis factor α (TNF-α) induced neuroinflammation. Conclusion: Silymarin and silibinin exert anti-depression and anxiolytic effects by regulating neurotransmitters, endocrine, neurogenesis, and immunologic systems. Therefore, as natural and complementary medicines, they can be used to reduce the symptoms of depression and anxiety; However, more clinical studies are needed in this field.