Journal Article

Oral Administration of Silibinin Ameliorates Cognitive Deficits of Parkinson’s Disease Mouse Model by Restoring Mitochondrial Disorders in Hippocampus

Chenkang Wang, Shunji Hattori, Takashi Ikejima, Hitomi Fujisaki, Jianing Fu, Siaoyu Song, Kazunori Mizuno, Xiumin Liu, Toshihiko Hayashi, Weiwei Liu

2021

Overview

Besides motor disorder, cognitive dysfunction is also common in Parkinson’s disease (PD). Essentially no causal therapy for cognitive dysfunction of PD exists at present. In this study, a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD was used to analyze the neuroprotective potential of orally administered silibinin, a proverbial hepatoprotective flavonoid derived from the herb milk thistle (Silybum marianum). Results demonstrated that silibinin administration significantly attenuated MPTP-induced cognitive impairment in behavioral tests. Nissl staining results showed that MPTP injection significantly increases the loss of neurons in the hippocampus. However, these mice were protected by oral administration of silibinin, accompanying reduction in the cell apoptosis in the hippocampus. The hippocampal aggregates of α-synuclein (α-syn) appeared in MPTP-injected mice, but were significantly decreased by silibinin treatment. MPTP injection induced oxidative stress, as evidenced by increased malondialdehyde (MDA) and decreased superoxide dismutase (SOD). The oxidative stress was alleviated by silibinin treatment. Mitochondrial disorder including the decline of mitochondrial membrane potential (MMP) was another signature in the hippocampus of MPTP-treated mice, accompanying increased mitochondrial fission and decreased fusion. Silibinin administration restored these mitochondrial disorders, as expected for the protection against MPTP injury. These findings suggest that silibinin has a potential to be further developed as a therapeutic candidate for cognitive dysfunction in PD.

• Publisher: Springer Science and Business Media LLC,Springer US,Springer Nature B.V
• Subject: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Administration, Oral / alpha-Synuclein / alpha-Synuclein - metabolism / Animals / Apoptosis / Apoptosis - drug effects / Biochemistry / Biomedical and Life Sciences / Biomedicine / Cell Biology / Cerebral Cortex / Cerebral Cortex - drug effects / Cerebral Cortex - pathology / Cognitive ability / Cognitive Dysfunction / Cognitive Dysfunction - chemically induced / Cognitive Dysfunction - drug therapy / Cognitive Dysfunction - metabolism / Cognitive Dysfunction - pathology / Disorders / Flavonoids / Hippocampus / Hippocampus - drug effects / Hippocampus - metabolism / Hippocampus - pathology / Male / Malondialdehyde / Memantine / Memantine - therapeutic use / Membrane potential / Mice / Mice, Inbred C57BL / Mitochondria / Mitochondria - drug effects / Mitochondrial Diseases / Mitochondrial Diseases - chemically induced / Mitochondrial Diseases - drug therapy / Mitochondrial Diseases - pathology / Morris Water Maze Test / Morris Water Maze Test - drug effects / Movement disorders / MPTP / Neurochemistry / Neurodegenerative diseases / Neurology / Neurons / Neurons - drug effects / Neuroprotection / Neuroprotective Agents / Neuroprotective Agents - administration & dosage / Neuroprotective Agents - therapeutic use / Neurosciences / Open Field Test / Open Field Test - drug effects / Oral administration / Original Paper / Oxidative Stress / Oxidative Stress - drug effects / Parkinson's disease / Parkinsonian Disorders / Parkinsonian Disorders - chemically induced / Parkinsonian Disorders - drug therapy / Parkinsonian Disorders - metabolism / Parkinsonian Disorders - pathology / Silibinin / Silybin / Silybin - administration & dosage / Silybin - therapeutic use / Superoxide dismutase / Synuclein