Network pharmacology-based approach to understand the effect and mechanism of chrysophanol against cognitive impairment in Wilson disease

Zhang, Xiao-yan; Wang, Xie; Ye, Ting; Shao, Nan; Wang, Jie; Cai, Biao; Xie, Dao-jun

doi:10.1007/s11011-023-01321-4

Cited by 3 publications

(1 citation statement)

References 33 publications

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“…To date, no drugs have been recommended for the treatment of WD-related cognitive impairment. Many studies have shown that anti-copper therapy can reduce copper deposition in the liver and brain, increase urinary copper content, and improve cognitive impairment in WD patients ( Wang et al, 2023 ; Zhang et al, 2024 ). An effective and safe means of nerve regulation, TMS has achieved curative effects in the treatment of WD complicated with dystonia ( Hao et al, 2021 ) and plays an important role in improving cognitive impairment with a variety of causes.…”

Section: Introductionmentioning

confidence: 99%

Effect of high-frequency repetitive transcranial magnetic stimulation on cognitive impairment in WD patients based on inverse probability weighting of propensity scores

Chen,

Wang,

Zhang

et al. 2024

Front. Neurosci.

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BackgroundHepatolenticular degeneration [Wilson disease (WD)] is an autosomal recessive metabolic disease characterized by copper metabolism disorder. Cognitive impairment is a key neuropsychiatric symptom of WD. At present, there is no effective treatment for WD-related cognitive impairment.MethodsIn this study, high-frequency repetitive transcranial magnetic stimulation (rTMS) was used to treat WD-related cognitive impairment, and inverse probability weighting of propensity scores was used to correct for confounding factors. The Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Auditory Verbal Learning Test (AVLT), Boston Naming Test (BNT), Clock Drawing Test (CDT) and Trail Making Test (TMT) were used to evaluate overall cognition and specific cognitive domains.ResultsThe MMSE, MoCA and CDT scores after treatment were significantly different from those before treatment (MMSE: before adjustment: OR = 1.404, 95% CI: 1.271–1.537; after adjustment: OR = 1.381, 95% CI: 1.265–1.497, p < 0.001; MoCA: before adjustment: OR = 1.306, 95% CI: 1.122–1.490; after adjustment: OR = 1.286, 95% CI: 1.104; AVLT: OR = 1.161, 95% CI: 1.074–1.248; after adjustment: OR = 1.145, 95% CI: 1.068–1.222, p < 0.05; CDT: OR = 1.524, 95% CI: 1.303–1.745; after adjustment: OR = 1.518, 95% CI: 1.294–1.742, p < 0.001). The BNT and TMT scores after adjustment were not significantly different from those before adjustment (BNT: before adjustment: OR = 1.048, 95% CI: 0.877–1.219; after adjustment: OR = 1.026, 95% CI: 0.863–1.189, p > 0.05; TMT: before adjustment: OR = 0.816, 95% CI: 1.122–1.490; after adjustment: OR = 0.791, 95% CI: 0.406–1.176, p > 0.05).ConclusionHigh-frequency rTMS can effectively improve cognitive impairment, especially memory and visuospatial ability, in WD patients. The incidence of side effects is low, and the safety is good.

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Section: Introductionmentioning

confidence: 99%

Effect of high-frequency repetitive transcranial magnetic stimulation on cognitive impairment in WD patients based on inverse probability weighting of propensity scores

Chen,

Wang,

Zhang

et al. 2024

Front. Neurosci.

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Exploring the therapeutic efficacy and pharmacological mechanism of Guizhi Fuling Pill on ischemic stroke: a meta-analysis and network pharmacology analysis

Wang,

Li,

Long

et al. 2024

Metab Brain Dis

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The roles of Guizhi Fuling Pills (GZFL) on the treatment of ischemic stroke (IS) are still controversial, and its pharmacological mechanism remains unclear. We aimed to investigate the e cacy of GZFL for IS and reveal the underlying mechanism using meta-analysis and network pharmacology methods. Eight electronic databases were searched up to November 20, 2023. A meta-analysis was conducted using Review Manager 5.4.1 software. The chemical compounds of GZFL were obtained using TCMSP, BATMAN-TCM, and ETCM, and their putative targets were predicted using Swiss Target Prediction database. IS-related targets were collected using DisGeNet, Genecards, and DrugBank. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed in the Metascape. Molecular docking was carried out using AutoDock Tools and PyMOL software. Compared with conventional medical treatment alone, GZFL plus conventional medical treatment could signi cantly improve the clinical total effective rate and NIHSS scores. The addition of GZFL also improved whole blood high shear viscosity, whole blood low shear viscosity, and plasma brinogen, TNFα and IL-6 levels. The top key active compounds included quercetin, kaempferol, catechin, and betasitosterol, and SRC, MAPK1, TP53, JUN, RELA, AKT1, and TNF were main core targets. GO analysis mainly included regulation of ion transport, cellular response to lipid, and in ammation response. The core pathways were enriched in lipid and atherosclerosis, cAMP, calcium, IL-17, and MAPK signaling pathways. The key active compounds had good a nity with the core targets. This study showed that GZFL displays anti-in ammatory, anti atherosclerosis and neuroprotective effects for IS patients.

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Therapeutic Targets and Natural Product Screening for Cognitive Impairments Associated with Ferroptosis in Wilson’s Disease

Wang,

Chen,

Zhang

et al. 2024

Am. J. Chin. Med.

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Wilson’s disease (WD) is a hereditary condition marked by abnormalities in copper metabolism, which precipitate a spectrum of neurological symptoms and cognitive impairments. Emerging research has highlighted ferroptosis (FPT) as a distinct type of programmed cell death, potentially linked to various cognitive dysfunctions. Nevertheless, the connection between FPT and cognitive impairment in Wilson’s disease (WDCI) remains largely enigmatic. In our study, we utilized a multifaceted approach, combining reverse network pharmacology, data mining, and molecular docking techniques to explore the potential for treating WDCI via FPT-related pathways. This thorough analysis revealed a series of proteins, including P38[Formula: see text], GSK3[Formula: see text], P53, GPX4, and PTGS2, as pivotal targets for WDCI treatment. Notably, Diosgenin (DG) has been identified as a prospective core component in this therapeutic framework. In the WD copper-loaded rat model, evaluations using the Morris water maze (MWM), Y maze, hematoxylin and eosin staining, transmission electron microscopy (TEM), and immunofluorescence (IF) detection showed that DG significantly enhanced cognitive function recovery, reduced structural damage to hippocampal neurons, and protected mitochondrial integrity. In addition, Western blot (WB) and quantitative reverse transcription PCR (qRT-PCR) analysis showed that DG significantly upregulated the expression levels of proteins and mRNA such as P38[Formula: see text], GSK3[Formula: see text], P53, GPX4, and PTGS2 in animal and cell models. Furthermore, DG effectively reversed the dysregulated expression of oxidative stress markers, including [Formula: see text], malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS). This study elucidates the neuroprotective effect of DG on hippocampal neurons by activating the P38[Formula: see text]-mediated FPT pathway, highlighting its efficacy as a potent monomer in traditional Chinese medicine and illuminating its potential role in the clinical treatment of WDCI.

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Network pharmacology-based approach to understand the effect and mechanism of chrysophanol against cognitive impairment in Wilson disease

Cited by 3 publications

References 33 publications

Effect of high-frequency repetitive transcranial magnetic stimulation on cognitive impairment in WD patients based on inverse probability weighting of propensity scores

Effect of high-frequency repetitive transcranial magnetic stimulation on cognitive impairment in WD patients based on inverse probability weighting of propensity scores

Exploring the therapeutic efficacy and pharmacological mechanism of Guizhi Fuling Pill on ischemic stroke: a meta-analysis and network pharmacology analysis

Therapeutic Targets and Natural Product Screening for Cognitive Impairments Associated with Ferroptosis in Wilson’s Disease

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