Effect of Mucuna pruriens on brain NMDA receptor and tau protein gene expression in cerebral ischemic rats

Parvatikar, Prachi P; Patil, Bheemshetty S.; Reddy, R Chandramouli; Bagoji, Ishwar B.; Kotennavar, Manjunath S.; Patil, S. M.; Patil, Aravind V.; Das, Kusal K.; Das, Swastika; Bagali, Shrilaxmi

doi:10.3389/fphys.2023.1092032

Cited by 5 publications

(1 citation statement)

References 33 publications

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“…It is now clear that post-ischemic brain neurodegeneration is a tauopathy [9,[45][46][47][48][49][50][51]. Some data suggest that in neurons and microglia, RAGE binds to the modified tau protein and facilitates the development of neuronal tau protein-related pathologies and behavioral deficits [28].…”

Section: Discussionmentioning

confidence: 99%

LRP1 and RAGE Genes Transporting Amyloid and Tau Protein in the Hippocampal CA3 Area in an Ischemic Model of Alzheimer’s Disease with 2-Year Survival

Pluta,

Kocki,

Bogucki

et al. 2023

Cells

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Explaining changes at the gene level that occur during neurodegeneration in the CA3 area is crucial from the point of view of memory impairment and the development of post-ischemic dementia. An ischemic model of Alzheimer’s disease was used to evaluate changes in the expression of genes related to amyloid transport in the CA3 region of the hippocampus after 10 min of brain ischemia with survival of 2, 7 and 30 days and 12, 18 and 24 months. The quantitative reverse transcriptase PCR assay revealed that the expression of the LRP1 and RAGE genes involved in amyloid transport was dysregulated from 2 days to 24 months post-ischemia in the CA3 area of the hippocampus. LRP1 gene expression 2 and 7 days after ischemia was below control values. However, its expression from day 30 to 24 months, survival after an ischemic episode was above control values. RAGE gene expression 2 days after ischemia was below control values, reaching a maximum increase 7 and 30 days post-ischemia. Then, after 12, 18 and 24 months, it was again below the control values. The data indicate that in the CA3 area of the hippocampus, an episode of brain ischemia causes the increased expression of the RAGE gene for 7–30 days during the acute phase and that of LRP1 from 1 to 24 months after ischemia during the chronic stage. In other words, in the early post-ischemic stage, the expression of the gene that transport amyloid to the brain increases (7–30 days). Conversely, in the late post-ischemic stage, amyloid scavenging/cleaning gene activity increases, reducing and/or preventing further neuronal damage or facilitating the healing of damaged sites. This is how the new phenomenon of pyramidal neuronal damage in the CA3 area after ischemia is defined. In summary, post-ischemic modification of the LRP1 and RAGE genes is useful in the study of the ischemic pathways and molecular factors involved in the development of Alzheimer’s disease.

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Section: Discussionmentioning

confidence: 99%

LRP1 and RAGE Genes Transporting Amyloid and Tau Protein in the Hippocampal CA3 Area in an Ischemic Model of Alzheimer’s Disease with 2-Year Survival

Pluta,

Kocki,

Bogucki

et al. 2023

Cells

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Effect of bioactive compounds of Mucuna pruriens on proteins of Wnt/β catenin pathway in pulmonary hypertension by in silico approach

Bhosle,

Bagali,

Parvatikar

et al. 2024

In Silico Pharmacol.

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Network pharmacology and molecular docking elucidate potential mechanisms of Eucommia ulmoides in hepatic ischemia–reperfusion injury

Ma,

Pan,

Wang

et al. 2023

Sci Rep

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Eucommia ulmoides (EU) and its diverse extracts have demonstrated antioxidative, anti-inflammatory, and cytoprotective properties against hepatic ischemia–reperfusion injury (HIRI). However, the primary constituents of EU and their putative mechanisms remain elusive. This study aims to explore the potential mechanisms of EU in the prevention and treatment of HIRI by employing network pharmacology and molecular docking methodologies. The main components and corresponding protein targets of EU were searched in the literature and TCMSP, and the compound target network was constructed by Cytoscape 3.9.1. Liver ischemia–reperfusion injury targets were searched in OMIM and GeneCards databases. The intersection points of compound targets and disease targets were obtained, and the overlapping targets were imported into the STRING database to construct the PPI network. We further analyzed the targets for GO and KEGG enrichment. Finally, molecular docking studies were performed on the core targets and active compounds. The component-target network unveiled a total of 26 efficacious bioactive compounds corresponding to 207 target proteins. Notably, the top-ranking compounds based on degree centrality were quercetin, β-sitosterol, and gallic acid. Within the PPI network, the highest degree centrality encompassed RELA, AKT1, TP53. GO and KEGG enrichment analysis elucidated that EU in HIRI primarily engaged in positive regulation of gene expression, positive transcriptional regulation via RNA polymerase II promoter, negative modulation of apoptotic processes, positive regulation of transcription from DNA templates, and drug responsiveness, among other biological processes. Key pathways included cancer pathways, RAGE signaling pathway, lipid metabolism, atherosclerosis, TNF signaling pathway, PI3K-Akt signaling pathway, and apoptotic pathways. Molecular docking analysis revealed robust affinities between quercetin, β-sitosterol, gallic acid, and RELA, AKT1, TP53, respectively. This study reveals EU exhibits substantial potential in mitigating and treating HIRI through multifaceted targeting and involvement in intricate signaling pathways.

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Effect of Mucuna pruriens on brain NMDA receptor and tau protein gene expression in cerebral ischemic rats

Cited by 5 publications

References 33 publications

LRP1 and RAGE Genes Transporting Amyloid and Tau Protein in the Hippocampal CA3 Area in an Ischemic Model of Alzheimer’s Disease with 2-Year Survival

LRP1 and RAGE Genes Transporting Amyloid and Tau Protein in the Hippocampal CA3 Area in an Ischemic Model of Alzheimer’s Disease with 2-Year Survival

Effect of bioactive compounds of Mucuna pruriens on proteins of Wnt/β catenin pathway in pulmonary hypertension by in silico approach

Network pharmacology and molecular docking elucidate potential mechanisms of Eucommia ulmoides in hepatic ischemia–reperfusion injury

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