Behavioral and biochemical investigations to explore the efficacy of quercetin and folacin in experimental diabetes induced vascular endothelium dysfunction and associated dementia in rats

Sharma, Poonam; Aggarwal, Khushboo; Awasthi, Rajendra; Kulkarni, Giriraj T.; Sharma, Bhupesh

doi:10.1515/jbcpp-2020-0159

Cited by 13 publications

(2 citation statements)

References 61 publications

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“…Quercetin exhibits a multi-faceted impact on vascular dementia, ameliorating endothelial dysfunction, behavioral aberrations, and biochemical disruptions, thereby attenuating the pathological manifestations of the condition [7,8]. Speci cally, quercetin induces an anti-in ammatory phenotype in microglial cells, leading to a reduction in demyelination within the ventral hippocampus (vHIP), thereby mitigating both vascular dementia and any concomitant neuropsychiatric symptoms [9].…”

Section: Discussionmentioning

confidence: 99%

Mechanisms underlying the therapeutic effects of banxiaxiexin decoction in treating vascular dementia based on network pharmacology and molecular docking

Liang,

Liu,

et al. 2023

Preprint

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Background The Banxiaxiexin decoction constitutes a prevalent Traditional Chinese Medicine (TCM) formulation employed for the therapeutic intervention of vascular dementia. Despite its routine clinical application, the underlying molecular mechanisms that mediate its pharmacological efficacy remain elusive. To address this lacuna, the present study employed a multi-pronged analytical approach involving network pharmacology and molecular docking techniques. Methods Active phytochemical constituents and relevant pharmacological targets of Banxiaxiexin decoction were elucidated using data procured from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Targets germane to vascular dementia were aggregated from a comprehensive range of databases, including GeneCards, Online Mendelian Inheritance in Man (OMIM), Drugbank, Pharmacogenomics Knowledge Base (PharmGKB), and Therapeutic Target Database (TTD). A Protein-Protein Interaction (PPI) network was constructed to isolate core targets. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were executed using METASCAPE. Tissue and organ-specific distribution of these targets were subsequently assessed. Molecular docking protocols were employed to evaluate the interactions between the identified potential targets and active constituents. Molecular dynamics simulations were conducted to further scrutinize the optimal core protein–compound complexes identified through molecular docking. Results A total of 133 active compounds and 64 putative targets of Banxiaxiexin decoction were identified. Topological analyses of the PPI network revealed a subset of 20 core targets. GO and KEGG pathway enrichment analyses substantiated that Banxiaxiexin decoction modulates genes implicated in pathways associated with oncogenesis, lipid metabolism and atherosclerosis, as well as Alzheimer's disease signaling pathways. Both molecular docking and molecular dynamics simulations affirmed a robust binding affinity between the active compounds and the isolated targets. Conclusions The present study adeptly elucidates the active components, prospective targets, and putative pathways implicated in the therapeutic efficacy of Banxiaxiexin decoction for vascular dementia. The data presented herein offer a novel methodological framework for the future investigation of the molecular mechanisms by which Banxiaxiexin decoction exerts its therapeutic effects. Furthermore, the delineated active constituents may serve as a propitious reservoir for subsequent drug development endeavors targeting vascular dementia.

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Section: Discussionmentioning

confidence: 99%

Mechanisms underlying the therapeutic effects of banxiaxiexin decoction in treating vascular dementia based on network pharmacology and molecular docking

Liang,

Liu,

et al. 2023

Preprint

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“…Most notably, ginsenoside Rb1 was reported to increase hippocampal antioxidant levels (Rui-xi et al, 2015;Zhu et al, 2019). Quercetin extracted from Euonymus alatus was similarly reported to increase acetylcholinesterase levels (Rui-xi et al, 2015;Sharma et al, 2021;Poonam et al, 2022).…”

Section: Effect On Cholinergic Levelsmentioning

confidence: 99%

Pharmaceutical and pharmacological studies of Shen Ma Yi Zhi granule for prevention of vascular dementia: A review

Chang

Liu

et al. 2022

Front. Neurosci.

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Background: With dementia significantly increasing hospitalization and disability rates, worldwide aging of the population presents major challenges to public health. The majority of cases of cognitive dysfunction among the elderly, however, are characterized by an identifiable, preventable and treatable vascular component. As such, increased study of preventative methods in the context of dementia is warranted. Traditional Chinese medicine compounds have been reported to be neuroprotective and improve cognitive function via a variety of mechanisms. Shen Ma Yi Zhi granule (SMYZG) is one such collection of compounds that has been proven clinically effective. Pharmacological mechanisms of action, pharmacokinetics and clinical applications of SMYZG have been previously studied using a variety of vascular dementia animal models. SMYZG activates and regulates four main signaling pathways relevant to vascular dementia including the AMPK/PPARα/PGC-1α/UCP2, Nrf2/HO-1, HIF-1/VEGF/Notch, and VEGF/Flk-1/p8 MAPK pathways. Furthermore, SMYZG influences anti-inflammatory and anti-oxidant stress responses, reverses demyelination of brain white matter and vascular endothelium, regulates pericyte function and normalizes mitochondrial metabolism. Neuroprotective effects of SMYZG, as well as those promoting regeneration of vascular endothelium, have also been reported in studies of rat models of vascular dementia. Future research concerning SMYG is warranted for development of vascular dementia preventative management strategies.

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Calcium Channels as a Potential Therapeutic Target for Alzheimer’s Disease

Sharma,

Thapak,

Chandwani

et al. 2023

Deciphering Drug Targets for Alzheimer’s Disease

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Behavioral and biochemical investigations to explore the efficacy of quercetin and folacin in experimental diabetes induced vascular endothelium dysfunction and associated dementia in rats

Cited by 13 publications

References 61 publications

Mechanisms underlying the therapeutic effects of banxiaxiexin decoction in treating vascular dementia based on network pharmacology and molecular docking

Mechanisms underlying the therapeutic effects of banxiaxiexin decoction in treating vascular dementia based on network pharmacology and molecular docking

Pharmaceutical and pharmacological studies of Shen Ma Yi Zhi granule for prevention of vascular dementia: A review

Calcium Channels as a Potential Therapeutic Target for Alzheimer’s Disease

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