Plant Compound May Lessen Cognitive Impairment, Mouse Study Suggests

Oral doses of silibinin — a plant compound sold as a dietary supplement — were found to lessen cognitive impairment in a mouse model of Parkinson’s disease.

It worked, according to researchers, by preventing neurodegeneration in the hippocampus, a brain region associated with cognitive function.

These neuroprotective effects were associated with a reduction in toxic alpha-synuclein clumps, mitochondrial transit impairments, and oxidative stress — all features of Parkinson’s — in the hippocampus. Moreover, the effects were comparable to those of memantine, an approved therapy for Alzheimer’s disease, the investigators said.

Along with previous preclinical studies suggesting that silibinin may ease motor symptoms of Parkinson’s, these early findings point to the plant compound as a potential therapy for the disease’s motor and non-motor symptoms.

Further studies are needed to confirm silibinin’s therapeutic potential in Parkinson’s, the researchers said.

The study, “Oral Administration of Silibinin Ameliorates Cognitive Deficits of Parkinson’s Disease Mouse Model by Restoring Mitochondrial Disorders in Hippocampus,” was published in the journal Neurochemical Research.

Progressive nerve cell loss in Parkinson’s disease is associated with the toxic buildup of toxic alpha-synuclein clumps, problems in mitochondria (the cells’ powerhouses), and high levels of oxidative stress.

Oxidative stress is an imbalance between the cell’s production of harmful free radicals and antioxidant molecules to detoxify them.

While motor symptoms are the most well-recognized hallmark of Parkinson’s disease, patients often experience cognitive problems, from mild cognitive impairment to Parkinson’s disease dementia.

Silibinin, a natural compound of the herb milk thistle, is sold as an over-the-counter dietary supplement for liver-related disorders, diabetes, indigestion, and other conditions. Previous preclinical studies have highlighted its neuroprotective properties and showed that the compound can lessen motor symptoms in a mouse model of Parkinson’s disease.

However, whether silibinin can also reduce Parkinson’s cognitive impairment remains unclear.

Now, a team of researchers in China and Japan evaluated the effects of oral administration of silibinin in Parkinson’s-associated cognitive impairment and neurologic deficits in the hippocampus, a brain region involved in learning and memory, in a induced mouse model of the disease.

For comparison, the researchers treated another group of these mice with memantine, an Alzheimer’s oral treatment shown to prevent cognitive decline in that patient population. It is also used off-label for the treatment of Parkinson’s-related dementia.

Results of validated behavioral tests showed that silibinin treatment lessened or prevented learning and memory defects characteristic of the Parkinson’s mouse model.

These beneficial effects were associated with a significant reduction in nerve cell damage and loss, and in the levels of alpha-synuclein clumps in the hippocampus, with nearly rescuing effects.

“The amelioration in damage of neuron in the hippocampus further supports the neuroprotective effects of silibinin,” the researchers wrote.

In addition, silibinin also prevented mitochondria dysfunction and oxidative stress in the mice’s hippocampus by boosting antioxidant responses, suggesting that the natural compound has both neuroprotective and antioxidant effects.

Notably, silibinin’s effects were similar to those observed with memantine.

These data highlight that “silibinin confers neuroprotection against cognitive dysfunction in PD [Parkinson’s disease] mice by improving mitochondrial dynamics, reducing oxidative stress, thereby alleviating hippocampal nerve [cell death] and improving cognitive impairment,” the researchers wrote.

They also suggest that silibinin “has a potential to be further developed as a therapeutic candidate for cognitive dysfunction in PD,” the team wrote, noting that this compound may be “more suitable for PD than memantine,” since the latter does not have an effect on motor symptoms.