Research shows that Zizyphi spinosi sperm can reduce brain aging and improve cognitive function in neurodegenerative disease models.
Study: Simply ground Zizyphi spinosi sperm prevents neurodegenerative diseases and reverses age-related cognitive decline in mice. Image credits: Leiter1940s/Shutterstock.com
In a recent study published on eLifea team of researchers evaluated the neuroprotective and rejuvenating effects of unextracted simple crush powder of Zizyphi spinosi sperm (ZSS) in preventing neurodegenerative diseases and improving cognitive function in aged mice.
Background
Neurodegenerative diseases, such as Alzheimer’s disease (AD), frontotemporal dementia (FTD), and Parkinson’s disease (PD), are characterized by the accumulation of amyloidogenic proteins such as amyloid beta (Aβ), tau, and α-synuclein, which form toxic aggregates forms. that disrupt synaptic function and propagate neuropathology.
This process leads to cognitive decline and motor impairment, which often begins decades before clinical symptoms. Cellular aging, driven by factors such as oxidative stress and telomere attrition, contributes to neurodegeneration by inducing a damaging inflammatory response.
Current drug development focuses on immunotherapy, which can be expensive and invasive. This highlights the need for safe, affordable and non-invasive preventive options. Further research is essential to explore effective nutritional interventions.
About the study
Dried ZSS is 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 unextracted simple crush powder was produced by sterilizing and grinding the dried ZSS and then sieving to obtain a fine powder. This powder was then heated in water and filtered, the resulting residue being dried under reduced pressure.
Component analysis for jujuboside A, jujuboside B, and spinosin in the ZSS preparations was performed by Japan Food Research Laboratories. The dried ZSS materials underwent methanol extraction and were analyzed using high-performance liquid chromatography (HPLC) coupled to mass spectrometry.
Mouse models of 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 were given oral administration of the extracts for one month, while control groups were given water.
Behavioral assessments were performed using the Morris water maze and rotarod tests, while histological analyzes examined neuropathology and markers of cellular aging. Oxidative stress was measured via Enzyme-Linked Immunosorbent Assay (ELISA) for 8-hydroxy-2′-deoxyguanosine.
The radical scavenging activity was evaluated using a superoxide dismutase assay kit. Statistical analyzes 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, 13-15 months old, show accumulation of Aβ oligomers and memory impairment. The extract was administered orally at a dose of 0.1 mg per injection for one month.
The results indicated an improvement in memory, although it was not yet fully recovered. A subsequent trial of a higher dose of 0.5 mg per injection in 15-16 month old APP23 mice led to significant improvement in memory, reaching levels comparable to those of non-transgenic littermates.
Immunohistochemical analysis revealed that the lower dosage significantly reduced Aβ oligomer levels and amyloid deposits in the cerebral cortex and hippocampus. Furthermore, synaptophysin levels in the hippocampal Cornu Ammonis areas 2 and 3 (CA2/3) were significantly increased after treatment.
The study then examined the impact of ZSS hot water extract on Tau784 mice, which exhibit tau pathology linked to frontotemporal dementia.
Administered at 0.1 and 0.5 mg per injection for one month, the higher dose resulted in full recovery of cognitive function to levels like those of 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, extractives and unextracted simple crush powder from ZSS showed that the simple crush powder significantly improved cognitive function beyond that of non-Tg littermates, while the hot water extract and extractives showed only moderate effects. .
Immunohistochemical analysis confirmed that all preparations reduced tau pathology, but the simple crush powder showed the strongest effects. In particular, 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 significantly reduce α-synuclein pathology. Furthermore, treatment increased BDNF expression in key brain regions and increased neurogenesis in the dentate gyrus and substantia nigra.
The positive cognitive effects observed in aged mice after treatment with ZSS’s simple crush powder suggested potential brain rejuvenating properties.
Cognitive assessments showed that treatment with ZSS significantly improved memory in older mice, bringing it in line with the cognitive levels of younger counterparts. Furthermore, key neuroprotective markers such as synaptophysin and BDNF were increased, along with increased neurogenesis.
Cellular senescence markers were assessed, showing 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), increasing its potential to counteract this to go further was supported. aging effects.
In addition, ZSS powder is reduced deoxyribonucleic acid (DNA) oxidation markers, indicating antioxidant activity, although the radical scavenging ability was relatively weak compared to known potent antioxidants.
Finally, analysis of ZSS components revealed lower concentrations of jujuboside A, jujuboside B, and spinosine in the simple crush powder compared to the extract.
When these compounds were tested as a mixture, they showed significantly weaker cognitive improvement than the full extract, indicating that ZSS likely contains other active compounds that contribute to its neuroprotective effects, which may be reduced during the extraction process.
Conclusions
In summary, the study revealed that ZSS, especially the unextracted simple crush powder, effectively alleviates 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.
Furthermore, ZSS powder reduced DNA oxidation and cellular senescence in old mice, improving cognitive performance to levels comparable to young mice.