Neuroprotective Potential of Silymarin against CNS Disorders: Insight into the Pathways and Molecular Mechanisms of Action

Abstract

Silymarin, a C25 containing flavonoid from the plant Silybum marianum, has been the gold standard drug to treat liver disorders associated with alcohol consumption, acute and chronic viral hepatitis, and toxin-induced hepatic failures since its discovery in 1960. Apart from the hepatoprotective nature, which is mainly due to its antioxidant and tissue regenerative properties, Silymarin has recently been reported to be a putative neuroprotective agent against many neurologic diseases including Alzheimer's and Parkinson's diseases, and cerebral ischemia. Although the underlying neuroprotective mechanism of Silymarin is believed to be due to its capacity to inhibit oxidative stress in the brain, it also confers additional advantages by influencing pathways such as β-amyloid aggregation, inflammatory mechanisms, cellular apoptotic machinery, and estrogenic receptor mediation. In this review, we have elucidated the possible neuroprotective effects of Silymarin and the underlying molecular events, and suggested future courses of action for its acceptance as a CNS drug for the treatment of neurodegenerative diseases.

Adolescent silymarin treatment increases anxiety-like behaviors in adult mice

“…As indicated earlier, previous studies have shown that SM treatment can increase serotonin levels in the PFC in mice (Lu et al, 2010;Borah et al, 2013). We and others have shown that the PFC and the serotoninergic system in the brain play important roles in regulating anxietyrelated behaviors in humans and rodents (Davidson, 2002;Akimova et al, 2009;Solati et al, 2011).…”

“…There is increasing evidence from clinical and experimental studies that silymarin (SM), a mixture of flavonolignans including silybin, silydianin, and silychristin extracted from the milk thistle (Silybum marianum), can be used as a hepatoprotective, antioxidative, antiinflammatory, or neuroprotective drug (for a review, see Borah et al, 2013). Previous studies have also indicated that SM can influence cytokine production, RNA and protein synthesis, scavenging of free radicals, and stabilization of the cell membrane (Gupta et al, 2000;Li et al, 2006;Wu et al, 2009;Patel et al, 2010;Muley et al, 2012).…”

Neuroprotective mechanism of the novel melatonin derivative Neu-P11 in brain ischemia related models

“…Several authors propose antioxidants as good neuroprotective agents for brain ischemia, even though some of them, edaravone, sylimarin, minocycline or quercetin, among others, have not shown efficacy in clinic (7,(42)(43)(44)(45)(46). In line with this, because melatonin is a direct and indirect antioxidant, it has been proposed as a neuroprotective agent (47) and it has shown to be a good candidate, as it has demonstrated neuroprotection against oxidative stress implied in different neurodegenerative diseases such as AD (48,49), PD (50,51), brain trauma (52) and…”

Immunomodulation as a neuroprotective and therapeutic strategy for Parkinson's disease

“…Many natural and/or endogenous compounds have recently been shown to be effective in rodent models of PD as well, such as resveratrol [26–28], tanshinone [29,30], silymarin [31–35], resolvins [36], diadzein [37], and apocynin derivatives [38,39]. The majority of these compounds act as both anti-inflammatory agents as well as anti-oxidants.…”