Silibinin attenuates motor dysfunction in a mouse model of Parkinson's disease by suppression of oxidative stress and neuroinflammation along with promotion of mitophagy

Liu, Xiumin; Liu, Weiwei; Wang, Chenkang; Chen, Yinzhe; Liu, Panwen; Hayashi, Toshihiko; Mizuno, Kazunori; Fujisaki, Hitomi; Ikejima, Takashi

doi:10.1016/j.physbeh.2021.113510

Cited by 32 publications

(17 citation statements)

References 78 publications

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“…Despite a lack of direct measurement of the permeability across the blood–brain barrier, several studies have reported the treatment effects of silibinin on neurological disorders after oral administration. For example, silibinin attenuated the loss of dopamine neurons and hippocampal neuron apoptosis in mice models of Parkinson’s disease [ 47 , 48 ]. Moreover, oral administration of silibinin (200 mg/kg) decreased Aβ deposition and the levels of soluble Aβ1–40/1–42 in the hippocampus by downregulating APP and BACE1 in the brains of APP/PS1 mice [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Silibinin Protects against H2O2-Induced Oxidative Damage in SH-SY5Y Cells by Improving Mitochondrial Function

Tie

et al. 2022

Antioxidants

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Oxidative stress plays a critical role in the pathogenesis of various neurodegenerative diseases. Increasing evidence suggests the association of mitochondrial abnormalities with oxidative stress-related neural damage. Silibinin, a natural flavonol compound isolated from Silybum marianum, exhibits multiple biological activities. The present study investigated the effects of silibinin on H2O2-induced oxidative stress in human neuroblastoma SH-SY5Y cells. Exposure to H2O2 (750 µM) reduced the viability of SH-SY5Y cells, which was coupled with increased reactive oxygen species (ROS), abnormal cell morphology, and mitochondrial dysfunction. Remarkably, silibinin (1, 5, and 10 µM) treatment attenuated the H2O2-induced cell death. Moreover, silibinin reduced ROS production and the levels of malondialdehyde (MDA), increased the levels of superoxide dismutase (SOD) and glutathione (GSH), and increased mitochondrial membrane potential. Moreover, silibinin normalized the expression of nuclear factor 2-related factor 2 (Nrf2)-related and mitochondria-associated proteins. Taken together, our findings demonstrated that silibinin could attenuate H2O2-induced oxidative stress by regulating Nrf2 signaling and improving mitochondrial function in SH-SY5Y cells. The protective effect against oxidative stress suggests silibinin as a potential candidate for preventing neurodegeneration.

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Section: Discussionmentioning

confidence: 99%

Silibinin Protects against H2O2-Induced Oxidative Damage in SH-SY5Y Cells by Improving Mitochondrial Function

Tie

et al. 2022

Antioxidants

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“…Dopaminergic nerve protection is achieved by stimulating mitophagy, which removes the detrimental consequences of damaged mitochondria. These data implied that silibinin has the potential to be further explored as a treatment option for PD [48]. In another study, silibinin significantly reduced the motor impairment and dopaminergic neuronal degeneration induced by MPTP.…”

Section: Polyphenols Effects On Mitochondria In Pdmentioning

confidence: 93%

“…In vitro: PC12 neuronal cells ↓Mitochondrial apoptotic pathway [102] In vitro: PC12 neuronal cells ↓Mitochondrial apoptotic signaling [48] Schisandrin Lignan In vivo: Rat cortical cells ↓Ca 2+ , ↓ROS, ↓cytochrome C [25] Ellagic acid…”

Section: Flavonementioning

confidence: 99%

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Targeting Mitochondria by Plant Secondary Metabolites: A Promising Strategy in Combating Parkinson’s Disease

Fakhri

Abdian

Zarneshan

et al. 2021

IJMS

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Parkinson’s disease (PD) is one of the most prevalent and debilitating neurodegenerative conditions, and is currently on the rise. Several dysregulated pathways are behind the pathogenesis of PD; however, the critical targets remain unclear. Accordingly, there is an urgent need to reveal the key dysregulated pathways in PD. Prevailing reports have highlighted the importance of mitochondrial and cross-talked mediators in neurological disorders, genetic changes, and related complications of PD. Multiple pathophysiological mechanisms of PD, as well as the low efficacy and side effects of conventional neuroprotective therapies, drive the need for finding novel alternative agents. Recently, much attention has been paid to using plant secondary metabolites (e.g., flavonoids/phenolic compounds, alkaloids, and terpenoids) in the modulation of PD-associated manifestations by targeting mitochondria. In this line, plant secondary metabolites have shown promising potential for the simultaneous modulation of mitochondrial apoptosis and reactive oxygen species. This review aimed to address mitochondria and multiple dysregulated pathways in PD by plant-derived secondary metabolites.

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“…Mutations in PINK and PARKIN genes have been related to the origin of familial PD, which can represent around 10% of the diagnosed forms of PD [112][113][114]. Interestingly, normalizing PINK and PARKIN activity through chemical agents restored mitophagy and cognitive impairment in ND models [13,115]. Additionally, PINK1 overexpression rescued mitochondrial dysfunction and restored the removal of defective mitochondria in transgenic animal models of AD and HD [11,12,116].…”

Section: Alteration Of Mitochondrial Dynamics In Niandnddsmentioning

confidence: 99%

Nanotechnology-Based Drug Delivery Strategies to Repair the Mitochondrial Function in Neuroinflammatory and Neurodegenerative Diseases

2021

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Mitochondria are vital organelles in eukaryotic cells that control diverse physiological processes related to energy production, calcium homeostasis, the generation of reactive oxygen species, and cell death. Several studies have demonstrated that structural and functional mitochondrial disturbances are involved in the development of different neuroinflammatory (NI) and neurodegenerative (ND) diseases (NI&NDDs) such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Remarkably, counteracting mitochondrial impairment by genetic or pharmacologic treatment ameliorates neurodegeneration and clinical disability in animal models of these diseases. Therefore, the development of nanosystems enabling the sustained and selective delivery of mitochondria-targeted drugs is a novel and effective strategy to tackle NI&NDDs. In this review, we outline the impact of mitochondrial dysfunction associated with unbalanced mitochondrial dynamics, altered mitophagy, oxidative stress, energy deficit, and proteinopathies in NI&NDDs. In addition, we review different strategies for selective mitochondria-specific ligand targeting and discuss novel nanomaterials, nanozymes, and drug-loaded nanosystems developed to repair mitochondrial function and their therapeutic benefits protecting against oxidative stress, restoring cell energy production, preventing cell death, inhibiting protein aggregates, and improving motor and cognitive disability in cellular and animal models of different NI&NDDs.

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Silibinin attenuates motor dysfunction in a mouse model of Parkinson's disease by suppression of oxidative stress and neuroinflammation along with promotion of mitophagy

Cited by 32 publications

References 78 publications

Silibinin Protects against H2O2-Induced Oxidative Damage in SH-SY5Y Cells by Improving Mitochondrial Function

Silibinin Protects against H2O2-Induced Oxidative Damage in SH-SY5Y Cells by Improving Mitochondrial Function

Targeting Mitochondria by Plant Secondary Metabolites: A Promising Strategy in Combating Parkinson’s Disease

Nanotechnology-Based Drug Delivery Strategies to Repair the Mitochondrial Function in Neuroinflammatory and Neurodegenerative Diseases

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