Study finds Zizyphi spinosi semen may reduce brain aging and improve cognitive function in neurodegenerative disease models.
Study: Simply crushed Zizyphi spinosi semen prevents neurodegenerative diseases and reverses age-related cognitive decline in mice. Image Credit: Leiter1940s/Shutterstock.com
In a recent study posted to eLife, a team of researchers evaluated the neuroprotective and rejuvenating effects of non-extracted simple crush powder of Zizyphi spinosi semen (ZSS) in preventing neurodegenerative diseases and enhancing cognitive function in aged mice.
Background
Neurodegenerative diseases, such as Alzheimer's disease (AD), frontotemporal dementia (FTD), and Parkinson's disease (PD), are marked by the accumulation of amyloidogenic proteins like amyloid beta (Aβ), tau, and α-synuclein, which form toxic aggregates that disrupt synaptic function and propagate neuropathology.
This process leads to cognitive decline and motor impairment, often beginning decades before clinical symptoms appear. Cellular senescence, driven by factors like oxidative stress and telomere attrition, contributes to neurodegeneration by inducing a damaging inflammatory response.
Current drug development focuses on immunotherapy, which can be costly and invasive. This highlights the need for safe, affordable, and non-invasive preventive options. Further research is essential to explore effective dietary interventions.
About the study
Dried ZSS was sourced from Auropure LifeScience Co., Ltd. in China. The hot water extract was prepared by boiling the dried ZSS in a water suspension for one hour, followed by filtration and spray-drying with dextrin to create the extract.
In the laboratory, the non-extracted simple crush powder was produced by sterilizing and crushing the dried ZSS, then sieving to obtain a fine powder. This powder was subsequently heated in water and filtered, with the resulting residue dried under reduced pressure.
Component analysis for jujuboside A, jujuboside B, and spinosin in the ZSS preparations was conducted by Japan Food Research Laboratories. The dried ZSS materials underwent methanol extraction and were analyzed using high-performance liquid chromatography (HPLC) coupled with mass spectrometry.
Mouse models for neurodegenerative diseases, including Amyloid Precursor Protein 23 (APP23), Tau784, and Human Alpha-Synuclein (Huα-Sy)A53T, were used to evaluate the effects of the ZSS preparations. Mice received oral administration of the extracts for one month, with control groups receiving water.
Behavioral assessments were performed using the Morris water maze and rotarod tests, while histological analyses examined neuropathology and markers of cellular senescence. Oxidative stress was measured via Enzyme-Linked Immunosorbent Assay (ELISA) for 8-hydroxy-2’-deoxyguanosine.
Radical-scavenging activity was evaluated using a superoxide dismutase assay kit. Statistical analyses were performed using Analysis of Variance (ANOVA), with significance set at p < 0.05.
Study results
The effects of ZSS hot water extract on cognitive function and Aβ pathology were assessed in APP23 mice, which model AD. These mice, aged 13-15 months, display Aβ oligomer accumulation and memory impairment. The extract was administered orally at a dosage of 0.1 mg per shot for one month.
Results indicated an improvement in memory, though not fully restored. A subsequent trial with a higher dose of 0.5 mg per shot in 15-16-month-old APP23 mice led to significant memory enhancement, reaching levels comparable to non-transgenic littermates.
Immunohistochemical analysis revealed that the lower dosage significantly reduced Aβ oligomer levels and amyloid deposits in the cerebral cortex and hippocampus. Additionally, synaptophysin levels in the hippocampal Cornu Ammonis areas 2 and 3 (CA2/3) regions were notably increased following treatment.
The study then examined the impact of ZSS hot water extract on Tau784 mice, which exhibit tau pathology related to frontotemporal dementia.
Administered at 0.1 and 0.5 mg per shot for one month, the higher dosage resulted in complete recovery of cognitive function to levels like non-transgenic (non-Tg) littermates, while the lower dose produced moderate effects. The treatment effectively reduced phosphorylated tau levels and tau oligomers in the hippocampus and cerebral cortex, with significant recovery of synaptophysin levels.
Further comparison of the hot water extract, extraction residue, and non-extracted simple crush powder of ZSS demonstrated that the simple crush powder markedly enhanced cognitive function beyond that of non-Tg littermates, while the hot water extract and extraction residue showed only moderate effects.
Immunohistochemical analysis confirmed that all preparations reduced tau pathology, but the simple crush powder exhibited the strongest effects. Notably, the simple crush powder significantly increased brain-derived neurotrophic factor (BDNF) levels, which are crucial for neuron health.
In Huα-Syn(A53T) mice, which model PD, the simple crush powder was shown to improve motor function and reduce α-synuclein pathology significantly. Furthermore, the treatment enhanced BDNF expression in key brain regions and increased neurogenesis in the dentate gyrus and substantia nigra.
The positive cognitive effects observed in aged mice following treatment with the simple crush powder of ZSS suggested potential brain-rejuvenating properties.
Cognitive assessments revealed that ZSS treatment significantly improved memory in aged mice, aligning it with the cognitive levels of younger counterparts. In addition, key neuroprotective markers such as synaptophysin and BDNF were elevated, along with increased neurogenesis.
Cellular senescence markers were assessed, revealing that ZSS treatment significantly reduced levels of Cyclin-Dependent Kinase Inhibitor 2A (p16INK4a), Cyclin-Dependent Kinase Inhibitor 1 (p21CIP1/WAF1), and Phosphorylated Histone H2AX (γH2AX), further supporting its potential to counteract aging effects.
Additionally, ZSS powder reduced deoxyribonucleic acid (DNA) oxidation markers, indicating antioxidant activity, although its radical-scavenging ability was relatively weak compared to known potent antioxidants.
Lastly, analysis of ZSS components revealed lower concentrations of jujuboside A, jujuboside B, and spinosin in the simple crush powder compared to the extract.
When these compounds were tested as a mixture, they demonstrated significantly weaker cognitive enhancement than the full extract, suggesting that ZSS likely contains other active substances that contribute to its neuroprotective effects, which may be diminished during the extraction process.
Conclusions
To summarize, the study revealed that ZSS, especially its non-extracted simple crush powder, effectively mitigates neurodegenerative diseases.
This powder significantly reduced Aβ, tau, and α-synuclein oligomers, restored synaptophysin levels, increased BDNF expression, promoted neurogenesis, and improved cognitive and motor functions in various mouse models.
Additionally, ZSS powder decreased DNA oxidation and cellular senescence in aged mice, enhancing cognitive performance to levels similar to those of young mice.
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