Simply crushed Zizyphi spinosi semen prevents neurodegenerative diseases and reverses age-related cognitive decline in mice
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Curated by eLife
eLife assessment
The authors made a useful finding that Zizyphi spinosi semen, a traditional Chinese medicine, has demonstrated excellent biological activity and potential therapeutic effects against Alzheimer's disease (AD). The researchers presented the effects, but the research evidence for the mechanism was incomplete. The main claims were only partially supported.
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Abstract
Neurodegenerative diseases are age-related disorders characterized by the cerebral accumulation of amyloidogenic proteins, and cellular senescence underlies their pathogenesis. Thus, it is necessary for preventing these diseases to remove toxic proteins, repair damaged neurons, and suppress cellular senescence. As a source for such prophylactic agents, we selected Zizyphi spinosi semen (ZSS), a medicinal herb used in traditional Chinese medicine. ZSS hot water extract ameliorated Aβ and tau pathology and cognitive impairment in mouse models of Alzheimer’s disease and frontotemporal dementia. Non-extracted ZSS simple crush powder showed stronger effects than the extract and improved α-synuclein pathology and cognitive/motor function in Parkinson’s disease model mice. Furthermore, when administered to normal aged mice, the ZSS powder suppressed cellular senescence, reduced DNA oxidation, promoted brain-derived neurotrophic factor expression and neurogenesis, and enhanced cognition to levels similar to those in young mice. The quantity of known active ingredients of ZSS, jujuboside A, jujuboside B, and spinosin, was not proportional to the nootropic activity of ZSS. These results suggest that ZSS simple crush powder is a promising dietary material for the prevention of neurodegenerative diseases and brain aging.Impact statementNon-extracted simple crush powder of Zizyphi spinosi semen has not only disease-preventing effects but also brain-rejuvenating effects in mice.
Article activity feed
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eLife assessment
The authors made a useful finding that Zizyphi spinosi semen, a traditional Chinese medicine, has demonstrated excellent biological activity and potential therapeutic effects against Alzheimer's disease (AD). The researchers presented the effects, but the research evidence for the mechanism was incomplete. The main claims were only partially supported.
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Reviewer #1 (Public review):
Summary:
The study shows that Zizyphi spinosi semen (ZSS), particularly its non-extracted simple crush powder, has significant therapeutic effects on neurodegenerative diseases. It removes Aβ, tau, and α-synuclein oligomers, restores synaptophysin levels, enhances BDNF expression and neurogenesis, and improves cognitive and motor functions in mouse AD, FTD, DLB, and PD models. Additionally, ZSS powder reduces DNA oxidation and cellular senescence in normal-aged mice, increases synaptophysin, BDNF, and neurogenesis, and enhances cognition to levels comparable to young mice.
Weaknesses:
(1) While the study demonstrates that ZSS has protective effects across a wide range of animal models, including AD, FTD, DLB, PD, and both young and aged mice, it is broad and lacks a detailed investigation into the underlying …
Reviewer #1 (Public review):
Summary:
The study shows that Zizyphi spinosi semen (ZSS), particularly its non-extracted simple crush powder, has significant therapeutic effects on neurodegenerative diseases. It removes Aβ, tau, and α-synuclein oligomers, restores synaptophysin levels, enhances BDNF expression and neurogenesis, and improves cognitive and motor functions in mouse AD, FTD, DLB, and PD models. Additionally, ZSS powder reduces DNA oxidation and cellular senescence in normal-aged mice, increases synaptophysin, BDNF, and neurogenesis, and enhances cognition to levels comparable to young mice.
Weaknesses:
(1) While the study demonstrates that ZSS has protective effects across a wide range of animal models, including AD, FTD, DLB, PD, and both young and aged mice, it is broad and lacks a detailed investigation into the underlying mechanisms. This is the most significant concern.
(2) The authors highlight that the non-extracted simple crush powder of ZSS shows more substantial effects than its hot water extract and extraction residue. However, the manuscript provides very limited data comparing the effects of these three extracts.
(3) The authors have not provided a rationale for the dosing concentrations used, nor have they tested the effects of the treatment in normal mice to verify its impact under physiological conditions.
(4) Regarding the assessment of cognitive function in mice, the authors only utilized the Morris Water Maze (MWM) test, which includes a five-day spatial learning training phase followed by a probe trial. The authors focused solely on the learning phase. However, it is relevant to note that data from the learning phase primarily reflects the learning ability of the mice, while the probe trial is more indicative of memory. Therefore, it is essential that probe trial data be included for a more comprehensive analysis. A justification should be included to explain why the latency of 1st is about 50s not 60s.
(5) The BDNF immunohistochemical staining in the manuscript appears to be non-specific.
(6) The central pathological regions in PD are the substantia nigra and striatum. Please replace the staining results from the cortex and hippocampus with those from these regions in the PD model.
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Reviewer #2 (Public review):
Summary:
The authors studied the effects of hot water extract, extraction residue, and non-extracted simple crush powder of ZSS in diseased or aged mice. It was found that ZSS played an anti-neurodegenerative role by removing toxic proteins, repairing damaged neurons, and inhibiting cell senescence.
Strengths:
The authors studied the effects of ZSS in different transgenic mice and analyzed the different states of ZSS and the effects of different components.
Weaknesses:
The authors' study lacked an in-depth exploration of mechanisms, including changes in intracellular signal transduction, drug targets, and drug toxicity detection.
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Reviewer #3 (Public review):
ZSS has been widely used in Traditional Chinese Medicine as a sleep-promoting herb. This study tests the effects of ZSS powder and extracts on AD, PD, and aging, and broad protective effects were revealed in mice.
However, this work did not include a mechanistic study or target data on ZSS were included, and PK data were also not involved. Mechanisms or targets and PK study are suggested. A human PK study is preferred over mice or rats. E.g. which main active ingredients and the concentration in plasma, in this context, to study the pharmacological mechanisms of ZSS.
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