Silibinin Attenuates MPP⁺-Induced Neurotoxicity in the Substantia NigraIn Vivo

Abstract

Parkinson's disease (PD) is characterized by degeneration of the nigrostriatal dopaminergic (DA) pathway. The cause of neuronal death in PD is largely unknown, but it is becoming clear that inflammation plays a significant role in the pathophysiology of PD. Silibinin is a major flavonoid in milk thistle which has an anti-inflammatory activity. We investigated whether silibinin could have neuroprotective effects on DA neurons in the 1-methyl-4-phenylpyridinium ion (MPP(+))-treated animal model of PD in vivo. To address this question, animals received intraperitoneal (i.p.) injections 10, 50, or 100 mg/kg of silibinin, starting 1 day before MPP(+) injection and continued daily until 6 days post-lesion for tyrosine hydroxylase (TH) staining, or until 1 hour prior to the MPP(+) injection to examine the expression levels of inflammatory proteins. Finally, their brains were harvested at the indicated time points for the analyses. Silibinin treatment with 10 mg/kg had no significantly neuroprotective effects in the substantia nigra (SN). However, 50 and 100 mg/kg of silibinin ameliorated the MPP(+)-induced neurotoxicity in the SN in a dose-dependent manner, and the increased levels of inflammatory molecules such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and inducible nitric oxide synthase (iNOS) by MPP(+) treatment were attenuated by treatment with 100 mg/kg of silibinin. These results indicate that silibinin could be a useful and beneficial natural product offering promise for the prevention of DA neuronal degeneration involved in PD.

Recent trends in the development of nanophytobioactive compounds and delivery systems for their possible role in reducing oxidative stress in Parkinson’s disease models

“…[37][38][39] Bioactive compounds play a major role in sustained protection against loss of dopaminergic neuron due to oxidative stress, among the various treatments to improve these symptoms in patients with PD. 3,36,[40][41][42][43] Extensive animal model studies have been conducted about the sustained protective role of different synthetic and natural bioactive compounds against dopaminergic neuron loss in PD. [44][45][46][47][48][49] Based on limitations for using synthetic compounds, [50][51][52] natural phytobioactive compounds play an important role in preventing PD.…”

“…43,[229][230][231][232] Silibinin protects against neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of PD by stabilizing mitochondria potential, antioxidative, and anti-neuroinflammatory reactions. 230 Similarly, silibinin attenuates mitochondrial dysfunction, oxidative stress, and neuronal loss following injection of MPP + in a rat model of PD.…”

“…229 Higher doses of silibinin enhance the protective effect in a 1-methyl-4-phenylpyridinium ion-treated animal model of PD in vivo. 43 However, the bioavailability of silibinin to various organs is limited but can be greatly enhanced by nanosizing the compound. 233,234 The bioavailability of silibinin-loaded nanotubes with a size range of 20-30 nm is greatly enhanced in cancer cell lines, even at very low concentrations.…”

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

“…Also, resveratrol causes an upregulation of suppressor of cytokine signaling (SOCS-1), and tanshinone treatment inhibited nitric oxide (NO) production, as well as NADPH and iNOS expression. In the MPTP model, silymarin treatment stabilizes mitochondrial membrane potential, decreases levels of TNFα, iNOS, and IL-1β, and ultimately, decreases striatal levels of caspase-3 and NF-κB indicating an anti-apoptotic and anti-inflammatory function [32,34,35]. Taken together, these findings help to justify the potential beneficial use of natural anti-inflammatory agents for the treatment of PD.…”

A Study of the Effects of Different Doses of Silymarin on Rotenone-Induced Rat Model of Parkinsonism.

“…iNOS and pro-inflammatory cytokines may be involved in nigrostriatal dopaminergic neuronal death. Increasing evidence suggests that activated microglia generate ROS, resulting in oxidative stress to dopaminergic neurons in the SN (Jung et al, 2014).…”