Ellagic acid and pentagalloylglucose are potential inhibitors of prion protein fibrillization

Yan, Chunjun; Zhou, Zheng

doi:10.1016/j.ijbiomac.2021.01.045

Cited by 7 publications

(7 citation statements)

References 63 publications

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“…For each ligand, the lowest binding energy was selected as the result of molecular docking. Lastly, the docking conformation analysis and mapping were carried out by PyMOL software, and PLIP ( https://projects.biotec.tu-dresden.de/plip-web/plip ) was used to analyze the force between ligands and proteins ( Yan and Zhou, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

Study on the Mechanism of Baimai Ointment in the Treatment of Osteoarthritis Based on Network Pharmacology and Molecular Docking with Experimental Verification

et al. 2021

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Purpose: The external preparation of the Tibetan medicine formula, Baimai ointment (BMO), has great therapeutic effects on osteoarthritis (OA). However, its molecular mechanism remains almost elusive. Here, a comprehensive strategy combining network pharmacology and molecular docking with pharmacological experiments was adopted to reveal the molecular mechanism of BMO against OA.Methods: The traditional Chinese medicine for systems pharmacology (TCMSP) database and analysis platform, traditional Chinese medicine integrated database (TCMID), GeneCards database, and DisGeNET database were used to screen the active components and targets of BMO in treating OA. A component–target (C-T) network was built with the help of Cytoscape, and the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment through STRING. Autodock Tools which was used to dock the key components and key target proteins was analyzed. Animal experiments were performed to verify the key targets of BMO. Hematoxylin–eosin and toluidine blue staining were used to observe the pathology of joints. Protein expression was determined using enzyme-linked immunosorbent assay.Results: Bioactive compounds and targets of BMO and OA were screened. The network analysis revealed that 17-β-estradiol, curcumin, licochalone A, quercetin, and glycyrrhizic acid were the candidate key components, and IL6, tumor necrosis factor (TNF), MAPK1, VEGFA, CXCL8, and IL1B were the candidate key targets in treating OA. The KEGG indicated that the TNF signaling pathway, NF-κB signaling pathway, and HIF-1 signaling pathway were the potential pathways. Molecular docking implied a strong combination between key components and key targets. The pathology and animal experiments showed BMO had great effects on OA via regulating IL6, TNF, MAPK1, VEGFA, CXCL8, and IL1B targets. These findings were consistent with the results obtained from the network pharmacology approach.Conclusion: This study preliminarily illustrated the candidate key components, key targets, and potential pathways of BMO against OA. It also provided a promising method to study the Tibetan medicine formula or external preparations.

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Section: Methodsmentioning

confidence: 99%

Study on the Mechanism of Baimai Ointment in the Treatment of Osteoarthritis Based on Network Pharmacology and Molecular Docking with Experimental Verification

et al. 2021

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“…Prion diseases, including Creutzfeldt–Jakob disease, Gerstmann–Sträussler–Scheinker syndrome, fatal familial insomnia, bovine spongiform encephalopathy, and scrapie, affect the cognition and behavior pattern of humans and other mammals. − Cellular prion protein (PrP C ) is a widespread glycoprotein anchored to the plasma membrane of cells with the help of glycosylphosphatidylinositol and is highly conserved in mammalian cells . The abnormal conformational transition of PrP C to scrapie prion protein (PrP Sc ) is thought to be a crucial infectious path of prion disorders. ,, The two isomers have different secondary structures, which leads to their different physicochemical properties. Compared to PrP C , PrP Sc has more β-sheets and fewer α-helix structures, and the self-assembly and accumulation of PrP Sc in the central nervous system of infected individuals cause neuronal cell death or dysfunction. , …”

Section: Introductionmentioning

confidence: 99%

Roles of Apigenin and Nepetin in the Assembly Behavior and Cytotoxicity of Prion Neuropeptide PrP106-126

Huo,

Zhao,

Wang

et al. 2023

ACS Chem. Neurosci.

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Development of potential inhibitors to prevent prion protein (PrP) fibrillation is a therapeutic strategy for prion diseases. The prion neuropeptide PrP106-126, a research model of abnormal PrP (PrP Sc ), presents similar physicochemical and biochemical characters to PrP Sc , which is also a target of potential inhibitors against prion deposition. Many flavones have antioxidant, anti-inflammatory, and antibacterial properties, and they are applied in treating prion disorder and other amyloidosis as well. However, the inhibition mechanism of flavones on PrP106-126 fibrillation is still unclear. In the current work, apigenin and nepetin were used to suppress the aggregation of PrP106-126 and to alleviate the peptide-induced cytotoxicity. The results showed that apigenin and nepetin impeded the fibril formation of PrP106-126 and depolymerized the preformed fibrils. They were bound to PrP106-126 predominantly by hydrophobic and hydrogen bonding interactions. In addition, both flavones upregulated cell viability and decreased membrane leakage through reducing peptide oligomerization. The differences in inhibition and cell protection between the two small molecules were presumably attributed to the substitution of hydroxyl and methoxy groups in nepetin, which demonstrated the significant structure−function relationship of flavones with prion neuropeptide and the prospect of flavonoids as drug candidates against prion diseases.

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“…EA has shown the potent inhibitory effect in collagen-activated platelet aggregation . Yan et al have revealed the effect of EA on prion protein fibrillization . Recently, Kumar et al indicated that EA inhibits aggregation of wild-type αS at multiple stages .…”

Section: Introductionmentioning

confidence: 99%

“…28 Yan et al have revealed the effect of EA on prion protein fibrillization. 29 Recently, Kumar et al indicated that EA inhibits aggregation of wild-type αS at multiple stages. 30 However, the present study aimed was to systematically assess the modulatory effect of EA against uninduced (wild-type αS) as well as mutation (A53T and E46K) and metal-induced aggregation of αS.…”

Section: Introductionmentioning

confidence: 99%

Ellagic Acid Modulates Uninduced as well as Mutation and Metal-Induced Aggregation of α-Synuclein: Implications for Parkinson’s Disease

Meena

Kumar

Karalia

et al. 2021

ACS Chem. Neurosci.

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α-Synuclein (αS) is an intrinsically disordered protein whose aggregation and deposition in Lewy bodies is involved in the progression of Parkinson's disease (PD) and other related disorders. The aggregation process of αS is also triggered by mutations like A53T and E46K in the SNCA gene and disruption in metal-ion homeostasis. Currently, there is no obviating therapy available in the market that could effectively prevent the progression of the disease. In this backdrop, there exists an emerging need to consider naturally occurring polyphenols and flavonoids as potential therapeutic agents against PD. In this study, we demonstrate the modulatory effect of ellagic acid (EA) against wild-type as well as mutation and metal-induced aggregation of αS. Thioflavin T (ThT) fluorescence assay suggests that EA acts on the nucleation phase of αS fibrillization, thereby increasing the lag phase from 21.33 ± 3.01 to 48.20 ± 5.05 h and reducing the fibrils growth rate from 4.60 ± 2.06 to 0.890 ± 0.36 h −1 . 8-Anilino-1-naphthalene sulfonic acid (ANS), Congo red (CR), and intrinsic fluorescence studies indicate that the interaction of EA with αS facilitates the structural changes in the protein that lead to inhibition of fibril formation. Dynamic light scattering (DLS) and transmission electron microscopy (TEM) images illustrate that the size of fibrils diminishes up to 100 nm in the presence of EA. Dot blot and seeding experiments put forward that EA directs the αS aggregation toward off-pathway fibrillization. Our 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay deciphers the role of EA in minimizing the αS fibril-induced toxicity, thereupon leading to an increase in cell viability. Also, EA attenuates both mutations as well as metal-induced αS fibrillization and disaggregates the preexisting fibrils. Additionally, computational studies elucidate that EA preferentially interacts with the N-terminal and NAC domain of αS. Hence, this work reveals the aggregation inhibition mechanism of EA and provides considerable therapeutic interventions against PD and related disorders.

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Ellagic acid and pentagalloylglucose are potential inhibitors of prion protein fibrillization

Cited by 7 publications

References 63 publications

Study on the Mechanism of Baimai Ointment in the Treatment of Osteoarthritis Based on Network Pharmacology and Molecular Docking with Experimental Verification

Study on the Mechanism of Baimai Ointment in the Treatment of Osteoarthritis Based on Network Pharmacology and Molecular Docking with Experimental Verification

Roles of Apigenin and Nepetin in the Assembly Behavior and Cytotoxicity of Prion Neuropeptide PrP106-126

Ellagic Acid Modulates Uninduced as well as Mutation and Metal-Induced Aggregation of α-Synuclein: Implications for Parkinson’s Disease

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