Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Front Endocrinol (Lausanne). 2024 Oct 23;15:1448119. doi: 
10.3389/fendo.2024.1448119. eCollection 2024.

Deciphering the role of lipid metabolism-related genes in Alzheimer's disease: a 
machine learning approach integrating Traditional Chinese Medicine.

Wu K(1), Liu Q(1), Long K(1), Duan X(1), Chen X(1), Zhang J(1), Li L(1), Li 
B(1).

Author information:
(1)Department of Geriatrics, Hospital of Chengdu University of Traditional 
Chinese Medicine, Chengdu, Sichuan, China.

BACKGROUND: Alzheimer's disease (AD) represents a progressive neurodegenerative 
disorder characterized by the accumulation of misfolded amyloid beta protein, 
leading to the formation of amyloid plaques and the aggregation of tau protein 
into neurofibrillary tangles within the cerebral cortex. The role of 
carbohydrates, particularly apolipoprotein E (ApoE), is pivotal in AD 
pathogenesis due to its involvement in lipid and cholesterol metabolism, and its 
status as a genetic predisposition factor for the disease. Despite its 
significance, the mechanistic contributions of Lipid Metabolism-related Genes 
(LMGs) to AD remain inadequately elucidated. This research endeavor seeks to 
bridge this gap by pinpointing biomarkers indicative of early-stage AD, with an 
emphasis on those linked to immune cell infiltration. To this end, advanced 
machine-learning algorithms and data derived from the Gene Expression Omnibus 
(GEO) database have been employed to facilitate the identification of these 
biomarkers.
METHODS: Differentially expressed genes (DEGs) were identified by comparing gene 
expression profiles between healthy individuals and Alzheimer's disease (AD) 
patients, using data from two Gene Expression Omnibus (GEO) datasets: GSE5281 
and GSE138260. Functional enrichment analysis was conducted to elucidate the 
biological relevance of the DEGs. To ensure the reliability of the results, 
samples were randomly divided into training and validation sets. The analysis 
focused on lipid metabolism-related DEGs (LMDEGs) to explore potential 
biomarkers for AD. Machine learning algorithms, including Support Vector 
Machine-Recursive Feature Elimination (SVM-RFE) and the Least Absolute Shrinkage 
and Selection Operator (LASSO) regression model, were applied to identify a key 
gene biomarker. Additionally, immune cell infiltration and its relationship with 
the gene biomarker were assessed using the CIBERSORT algorithm. The Integrated 
Traditional Chinese Medicine (ITCM) database was also referenced to identify 
Chinese medicines related to lipid metabolism and their possible connection to 
AD. This comprehensive strategy aims to integrate modern computational methods 
with traditional medicine to deepen our understanding of AD and its underlying 
mechanisms.
RESULTS: The study identified 137 genes from a pool of 751 lipid 
metabolism-related genes (LMGs) significantly associated with autophagy and 
immune response mechanisms. Through the application of LASSO and SVM-RFE 
machine-learning techniques, four genes-choline acetyl transferase (CHAT), 
member RAS oncogene family (RAB4A), acyl-CoA binding domain-containing protein 6 
(ACBD6), and alpha-galactosidase A (GLA)-emerged as potential biomarkers for 
Alzheimer's disease (AD). These genes demonstrated strong therapeutic potential 
due to their involvement in critical biological pathways. Notably, nine Chinese 
medicine compounds were identified to target these marker genes, offering a 
novel treatment approach for AD. Further, ceRNA network analysis revealed 
complex regulatory interactions involving these genes, underscoring their 
importance in AD pathology. CIBERSORT analysis highlighted a potential link 
between changes in the immune microenvironment and CHAT expression levels in AD 
patients, providing new insights into the immunological dimensions of the 
disease.
CONCLUSION: The discovery of these gene markers offers substantial promise for 
the diagnosis and understanding of Alzheimer's disease (AD). However, further 
investigation is necessary to validate their clinical utility. This study 
illuminates the role of Lipid Metabolism-related Genes (LMGs) in AD 
pathogenesis, offering potential targets for therapeutic intervention. It 
enhances our grasp of AD's complex mechanisms and paves the way for future 
research aimed at refining diagnostic and treatment strategies.

Copyright © 2024 Wu, Liu, Long, Duan, Chen, Zhang, Li and Li.

DOI: 10.3389/fendo.2024.1448119
PMCID: PMC11538058
PMID: 39507054 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare that the research was 
conducted in the absence of any commercial or financial relationships that could 
be construed as a potential conflict of interest.


2. J Ethnopharmacol. 2024 Nov 4:119016. doi: 10.1016/j.jep.2024.119016. Online 
ahead of print.

Dengzhan Shengmai Capsule Ameliorates Cognitive Impairment via Inhibiting ER 
stress in APP/PS1 Mice.

Ma HH(1), Zheng JY(2), Qiu YH(3), Su S(4), Lu FM(5), Wu GL(6), Zhang SJ(7), Cai 
YF(8).

Author information:
(1)State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second 
Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 
510405, China; Department of Neurology, The Second Affiliated Hospital of 
Guangzhou University of Chinese Medicine, Guangzhou, China; Department of 
Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. 
Electronic address: 20202110044@stu.gzucm.edu.cn.
(2)State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second 
Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 
510405, China; Department of Neurology, The Second Affiliated Hospital of 
Guangzhou University of Chinese Medicine, Guangzhou, China; Department of 
Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. 
Electronic address: zhengjiayi@gzucm.edu.cn.
(3)Department of Neurology, The Second Affiliated Hospital of Guangzhou 
University of Chinese Medicine, Guangzhou, China; Department of Neurology, 
Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. Electronic 
address: 383664259@qq.com.
(4)Department of Neurology, The Second Affiliated Hospital of Guangzhou 
University of Chinese Medicine, Guangzhou, China; Department of Neurology, 
Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. Electronic 
address: sushan@stu.gzucm.edu.cn.
(5)Department of Neurology, The Second Affiliated Hospital of Guangzhou 
University of Chinese Medicine, Guangzhou, China; Department of Neurology, 
Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China.
(6)State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second 
Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 
510405, China; Department of Neurology, The Second Affiliated Hospital of 
Guangzhou University of Chinese Medicine, Guangzhou, China. Electronic address: 
gliang_w@163.com.
(7)State Key Laboratory of Traditional Chinese Medicine Syndrome, The Second 
Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 
510405, China; Department of Neurology, The Second Affiliated Hospital of 
Guangzhou University of Chinese Medicine, Guangzhou, China; Department of 
Neurology, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. 
Electronic address: shijiezhang@gzucm.edu.cn.
(8)Department of Neurology, The Second Affiliated Hospital of Guangzhou 
University of Chinese Medicine, Guangzhou, China; Department of Neurology, 
Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China. Electronic 
address: caiyefeng@126.com.

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is a common type of 
neurodegenerative disease with the β-amyloid plaques (Aβ) deposition. 
Previously, Dengzhan Shengmai capsule (DZSM) has been shown to reduce the 
pathology associated with AD, but the underlying mechanism is unclear.
AIM OF STUDY: This study investigated the potential mechanisms of DZSM against 
AD.
MATERIALS AND METHODS: The six-month-old wild-type male mice and APP/PS1 double 
transgenic male mice were administered 0.9 % saline or DZSM for 8 weeks by 
gavage. Open field test, new object recognition test, and Morris Water maze test 
were used to assess spatial learning and memory. Aβ plaques in brains were 
visualized using ThT staining. Nissl staining, TUNEL staining, and western blot 
analyses were used to detect the neuronal function and apoptosis level. The 
superoxide dismutase (SOD), glutathione peroxidase assay kit (GSH-Px), and 
malondialdehyde (MDA) kits were performed to assess oxidative stress levels. 
Then, immunofluorescence and western blot analysis were applied to evaluate ER 
stress pathway protein levels. Finally, HT22 cells were treated by Aβ1-42 with 
or without DZSM medicated serum. Cell viability was assessed using the CCK-8 
assay, and western blot analysis was applied to evaluate ER stress pathway 
protein levels.
RESULTS: Open filed test, new object recognition test and Morris Water maze test 
showed that DZSM restored cognitive disorders in APP/PS1 mice. 
Immunohistochemistry and Thioflavin T staining results indicated that DZSM 
reduced Aβ plaques in the brain. Deeper and denser Nissl bodies were found in 
APP/PS1 mice after DZSM administration. Besides, APP/PS1 mice treated with DZSM 
showed a lower level of TUNEL and Bax/Bcl-2 ratio. DZSM improved the 
acetylcholine (ACh), choline acetyltransferase (ChAT), superoxide dismutase 
(SOD), and glutathione peroxidase (GSH-Px) activity while reducing 
acetylcholinesterase (AChE) and malondialdehyde (MDA) activity. In addition, the 
levels of ER stress pathway containing Phospho-PKR-like ER kinase (P-PERK), 
phosphorylate eukaryotic initiation factor 2 (P-eIF2α), activating transcription 
factor 4 (ATF4), glutamine-rich protein 1 (QRICH1), phosphorylate 
inositol-requiring protein 1α (P-IRE1α), the spliced form of X-box binding 
protein 1 (XBP1s), activating transcription factor-6 (ATF6) and C/EBP homologous 
binding protein (CHOP) were decreased by DZSM. CCK-8 results indicated that DZSM 
medicated serum played cytoprotective effects on Aβ1-42-induced HT22 cells. 
Western blot results suggested DZSM possibly inhibited ER stress pathways in 
Aβ1-42-induced HT22 cells.
CONCLUSION: The potential protective mechanism of DZSM on cognitive impairment 
in AD might be related to ER stress pathways.

Copyright © 2024. Published by Elsevier B.V.

DOI: 10.1016/j.jep.2024.119016
PMID: 39505222

Conflict of interest statement: Declaration of Competing Interest The authors 
declare no competing interests.


3. Neurosurg Rev. 2024 Nov 6;47(1):837. doi: 10.1007/s10143-024-03071-y.

Prognostic value of computed tomography and magnetic resonance imaging findings 
in acute traumatic brain injury in prediction of poor neurological outcome and 
mortality: a systematic review and meta-analysis.

Naeimi A(1), Aghajanian S(2), Jafarabady K(3)(4), Aletaha R(5), Maroufi 
SF(6)(7), Khorasanizadeh M(8), Stippler M(9).

Author information:
(1)Student Research Committee, School of Medicine, Guilan University of Medical 
Sciences, Rasht, Iran.
(2)Neuroscience Research Center, Iran University of Medical Sciences, Tehran, 
Iran.
(3)Student Research Committee, School of Medicine, Alborz University of Medical 
Sciences, Karaj, Iran.
(4)Department of Neurosurgery, School of Medicine, Alborz University of Medical 
Sciences, Karaj, Iran.
(5)Student Research Committee, Tabriz University of Medical Sciences, Tabriz, 
Iran.
(6)Neurosurgical Research Network (NRN), Universal Scientific Education and 
Research Network (USERN), Tehran, Iran.
(7)School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
(8)Department of Neurosurgery, Medical College of Wisconsin, Milwaukee, WI, USA. 
mirhojjax@yahoo.com.
(9)Division of Neurosurgery, Beth Israel Deaconess Medical Center, Harvard 
Medical School, Boston, MA, USA. mstipple@bidmc.harvard.edu.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality, 
impacting healthcare systems and economies. Early identification of poor 
outcomes is crucial for effective treatment. This systematic review assesses the 
prognostic value of computed tomography (CT) and magnetic resonance imaging 
(MRI) findings in predicting poor neurological outcomes and mortality in the 
acute phase of TBI. A comprehensive search of Scopus, MEDLINE, and Web of 
science databases was performed to identify studies examining CT and MR-based 
imaging findings and their association with poor outcomes as assessed by Glasgow 
outcome score as well as mortality within the early acute phase of TBI following 
injury/admission. Qualitative evaluation of included studies revealed several 
imaging sequences that modify the outcome of the patients, including extra-axial 
and intra-axial hemorrhage, swirl sign, contrast extravasation, midline shift, 
closed and open cranial cisterns, signs of edema, presence of cranial fractures, 
intracranial hemorrhage, cerebral microbleeds, diffuse axonal injury, apparent 
diffusion coefficient and fractional anisotropy in diffusion tensor imaging, as 
well as, concentrations of brain metabolites(N-acetyl aspartate, Creatinine, 
Choline, Myo-inositol, glutamate, and glutamine) in magnetic resonance 
spectroscopy. Among these markers, subarachnoid hemorrhage (SAH) and subdural 
hematoma (SDH) emerged as the most predictive of poor outcomes based on 
meta-analysis findings. SAH was significantly associated with an increased risk 
of mortality (OR: 3.35, 95% CI: 2.41-4.65, I²=51.3%) and poor outcomes (OR: 
2.69, 95% CI: 2.44-2.96, I²=0%). Similarly, SDH correlated with higher mortality 
risk (OR: 2.44, 95% CI: 2.14-2.78, I²=0%) and worse outcomes (OR: 2.00, 95% CI: 
1.12-3.59, I²=60.9%). In contrast, epidural hematoma (EDH) was linked to better 
outcomes (OR: 0.60, 95% CI: 0.52-0.68, I²=0%) but not significantly associated 
with mortality (OR: 0.38, 95% CI: 0.09-1.65, I²=73.7%). The results of this 
systematic review and meta-analysis provide an overview of clinically feasible 
imaging markers of prognostic value and may inform clinical decision-making in 
the future.

© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, 
part of Springer Nature.

DOI: 10.1007/s10143-024-03071-y
PMID: 39503919 [Indexed for MEDLINE]


4. Appl Environ Microbiol. 2024 Nov 6:e0122124. doi: 10.1128/aem.01221-24. Online
 ahead of print.

Acidification-based mineral weathering mechanism involves a 
glucose/methanol/choline oxidoreductase in Caballeronia mineralivorans PML1(12).

Blanco Nouche C(1)(2), Picard L(1)(2), Cochet C(2), Paris C(3), Oger P(4), 
Turpault M-P(2), Uroz S(1)(2).

Author information:
(1)Université de Lorraine, INRAE, « UMR1136 Interactions Arbres-Microorganismes 
», Nancy, France.
(2)INRAE, UR1138 « Biogéochimie des Ecosystèmes Forestiers », Champenoux, 
France.
(3)Université de Lorraine, EA 4367 « Laboratoire d'Ingénierie des Biomolécules 
», Ecole Nationale Supérieure d'Agronomie et des Industries Alimentaires 
(ENSAIA), Vandoeuvre-lès-Nancy, France.
(4)INSA Lyon, Université Claude Bernard Lyon 1, CNRS UMR5240, Villeurbanne, 
France.

While mineral weathering (MWe) plays a key role in plant growth promotion and 
soil fertility, the molecular mechanisms and the genes used by bacteria to 
weather minerals remain poorly characterized. Acidification-based dissolution is 
considered the primary mechanism used by bacteria. This mechanism is 
historically associated with the conversion of glucose to protons and gluconic 
acid through the action of particular glucose dehydrogenases (GDH) dependent on 
the pyrroquinoline quinone (PQQ) cofactor. Recently, bacteria lacking the 
GDH-PQQ system have been shown to perform the same enzymatic conversion with a 
glucose/methanol/choline (GMC) FAD-dependent oxidoreductase. Determining whether 
this particular enzyme is specific or widespread is especially important in 
terms of ecology and evolution. Genome analysis of the effective MWe strain 
Caballeronia mineralivorans PML1(12) revealed the presence of both systems 
(i.e., GDH-PQQ and several GMC oxidoreductases). The combination of mutagenesis, 
functional assays, and geochemical analyses demonstrated the key role of one of 
these GMC oxidoreductases in the mineral weathering ability of strain PML1(12) 
and the importance of the carbon source metabolized. Mass spectrometry confirmed 
the conversion of glucose to gluconic acid. Phylogenetic analyses highlighted a 
good relatedness of this new GMC oxidoreductase with GMC oxidoreductases 
presenting a GDH activity in Burkholderia cepacia and Collimonas pratensis and 
conferring its mineral weathering ability to the last one. Together, our 
analyses expand the number of bacteria capable of weathering minerals using GMC 
oxidoreductases, showing that such enzymes are not restricted to Collimonas.
IMPORTANCE: This work deciphers the molecular and genetic bases used by strain 
PML1(12) of Caballeronia mineralivorans to weather minerals. Through 
bioinformatics analyses, we identified a total of four GMC-FAD oxidoreductases 
in the genome of strain PML1(12) and a putative PQQ-dependent glucose 
dehydrogenase. Through a combination of physiological and geochemical analyses, 
we revealed that one of them (i.e., GMC3) was the enzyme responsible for the 
acidification-based mineral weathering mechanism used by strain PML1(12). To 
date, a single representative of this enzyme family has been identified in the 
effective mineral-weathering bacterial strain Collimonas pratensis PMB3(1). 
Phylogenetic analyses revealed that this new system appeared conserved in the 
Collimonas genus. The new findings presented in this work demonstrate that GMC 
oxidoreductases can have an active role in other effective MWe bacteria outside 
of collimonads and that Caballeronia are capable of weathering minerals using 
this type of enzyme. Our findings offer relevant information for different 
fields of research, such as environmental genomics, microbiology, chemistry, 
evolutionary biology, and soil sciences.

DOI: 10.1128/aem.01221-24
PMID: 39503492


5. Mediators Inflamm. 2024 Oct 28;2024:4777789. doi: 10.1155/2024/4777789. 
eCollection 2024.

The AMPK-mTOR Pathway Is Inhibited by Chaihu Shugan Powder, Which Relieves 
Nonalcoholic Steatohepatitis by Suppressing Autophagic Ferroptosis.

Liang Z(1), Pi D(1), Zhen J(1), Yan H(1), Zheng C(1), Liang Chen J(1), Fan W(1), 
Song Q(1), Pan J(1), Liu D(1), Pan M(1), Yang Q(1), Zhang Y(1).

Author information:
(1)Jinan University, Guang Zhou 510632, China.

Nonalcoholic steatohepatitis (NASH) is the advanced stage of nonalcoholic fatty 
liver disease (NAFLD), which is distinguished by the accumulation of fat in the 
liver, damage to liver cells, and inflammation. Chaihu Shugan powder (CSP), a 
renowned traditional Chinese medicine (TCM) blend extensively utilized in China 
to address liver disease, has demonstrated its efficacy in reducing lipid 
buildup and effectively combating inflammation. Hence, the primary objective of 
this research is to examine the impacts and possible mechanisms of CSP on NASH 
through assessments of liver histopathology, lipidomic analysis, and gene 
expression. To induce a mouse model of NASH, we employed a diet which deficient 
in methionine and choline, known as methionine-choline deficient (MCD) diet. 
Initially, we examined the impact of administering CSP to NASH mice by assessing 
the levels of serum and liver indicators. We found that CSP was able to reduce 
lipid buildup and inflammation in mice. In addition, a total of 1009 genes 
exhibited enrichment in both the autophagy and ferroptosis pathways. The liver 
protein levels of Adenosine monophosphate-activated protein kinase-mammalian 
target of rapamycin (AMPK-mTOR)-mediated autophagy and ferroptosis markers, such 
as p-AMPKα/AMPKα, p-mTOR/mTOR, Beclin-1, microtubule associated protein 1 light 
chain 3 gamma (LC3), p62 (sequestosome 1 [SQSTM1/p62]), Kelch-like 
ECH-associated protein 1 (KEAP1), nuclear factor erythroid 2-related factor 2 
(Nrf-2), ferritin heavy chain 1 (FTH1), and glutathione peroxidase 4 (GPX4), 
were restored by CSP. Furthermore, our findings indicated that the suppression 
of autophagy had a repressive impact on the occurrence of ferroptosis in the 
mouse model, indicating that autophagy activation likely plays a role in 
mediating ferroptosis in NASH.

Copyright © 2024 Zheng Liang et al.

DOI: 10.1155/2024/4777789
PMCID: PMC11535263
PMID: 39502754 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no conflicts of interest.