A Poloxamer-407 modified liposome encapsulating epigallocatechin-3-gallate in the presence of magnesium: Characterization and protective effect against oxidative damage

Minnelli, Cristina; Moretti, Paolo; Fulgenzi, Gianluca; Mariani, Paolo; Laudadio, Emiliano; Armeni, Tatiana; Galeazzi, Roberta; Mobbili, Giovanna

doi:10.1016/j.ijpharm.2018.10.004

Cited by 39 publications

(21 citation statements)

References 48 publications

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“…As previously reported, even though the EGCG structure enables it to interact with the the polar heads of phospholipids present in the bilayer [15,51], only part of EGCG molecules is efficiently bound to the lipid mambrane. Part of EGCG molecules lies in the water phase, thus able to react with the radicals generated from AAPH decomposition, preventing them to interact with membrane lipids.…”

Section: Structural Insight Of C18-egcg Inside Lipid Bilayer: In Silimentioning

confidence: 61%

Monoalkylated Epigallocatechin-3-gallate (C18-EGCG) as Novel Lipophilic EGCG Derivative: Characterization and Antioxidant Evaluation

et al. 2020

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Epigallocatechin-3-gallate (EGCG) has the highest antioxidant activity compared to the others catechins of green tea. However, the beneficial effects are mainly limited by its poor membrane permeability. A derivatization strategy to increase the EGCG interaction with lipid membranes is considered as one feasible approach to expand its application in lipophilic media, in particular the cellular absorption. At this purpose the hydrophilic EGCG was modified by inserting an aliphatic C18 chain linked to the gallate ring by an ethereal bond, the structure determined by NMR (Nuclear Magnetic Resonance) and confirmed by Density Functional Theory (DFT) calculations. The in vitro antioxidant activity of the mono-alkylated EGCG (C18-EGCG) was studied by the DPPH and Thiobarbituric Acid Reactive Substances (TBARS) assays, and its ability to protect cells towards oxidative stress was evaluated in Adult Retinal Pigmented Epithelium (ARPE-19) cells. Molecular Dynamics (MD) simulation and liposomal/buffer partition were used to study the interaction of the modified and unmodified antioxidants with a cell membrane model: the combined experimental-in silico approach shed light on the higher affinity of C18-EGCG toward lipid bilayer. Although the DPPH assay stated that the functionalization decreases the EGCG activity against free radicals, from cellular experiments it resulted that the lipid moiety increases the antioxidant protection of the new lipophilic derivative.

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Section: Structural Insight Of C18-egcg Inside Lipid Bilayer: In Silimentioning

confidence: 61%

Monoalkylated Epigallocatechin-3-gallate (C18-EGCG) as Novel Lipophilic EGCG Derivative: Characterization and Antioxidant Evaluation

et al. 2020

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“…Therefore, the assessment of the molecular basis of the inhibition is crucial to better understand the mechanisms of resistance to these agents and to identify new and less toxic TKIs. Among the natural anticancer agents, Epigallocatechin-3-gallate (EGCG), a major biologically active constituent of green tea, is known to produce several beneficial effects in human health [18]. It acts as inhibitor that competes for ATP binding site of EGFR cytoplasmic domain, in erlotinib-sensitive (wild type and ELREA deletion form) and -resistant cell lines in which the secondary T790M mutation is present (EGFR L858R-T790M) [19].…”

Section: Introductionmentioning

confidence: 99%

Conformational Insight on WT- and Mutated-EGFR Receptor Activation and Inhibition by Epigallocatechin-3-Gallate: Over a Rational Basis for the Design of Selective Non-Small-Cell Lung Anticancer Agents

Minnelli

Laudadio

Mobbili

et al. 2020

IJMS

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Non-small cell lung cancer (NSCLC) represents a difficult condition to treat, due to epidermal growth factor receptor (EGFR) kinase domain mutations, which lead to ligand-independent phosphorylation. Deletion of five amino acids (ELREA) in exon 19 and mutational change from leucine to arginine at position 858 (L858R) are responsible for tyrosine kinase domain aberrant activation. These two common types of EGFR-mutated forms are clinically associated with high response with Tyrosine Kinase Inhibitors (TKI); however, the secondary T790M mutation within the Tyrosine Kinase Domain (TKD) determines a resistance to these EGFR-TKIs. Using molecular dynamic simulation (MD), the present study investigated the architectural changes of wild-type and mutants EGFR’s kinase domains in order to detect any conformational differences that could be associated with a constitutively activated state and thus to evaluate the differences between the wild-type and its mutated forms. In addition, in order to evaluate to which extent the EGFR mutations affect its inhibition, Epigallocatechin 3-Gallate (EGCG) and Erlotinib (Erl), known EGFR-TKI, were included in our study. Their binding modes with the EGFR-TK domain were elucidated and the binding differences between EGFR wild-type and the mutated forms were evidenced. The aminoacids mutations directly influence the binding affinity of these two inhibitors, resulting in a different efficacy of Erl and EGCG inhibition. In particular, for the T790M/L858R EGFR, the binding modes of studied inhibitors were compromised by aminoacidic substitution confirming the experimental findings. These results may be useful for novel drug design strategies targeting the dimerization domain of the EGFR mutated forms, thus preventing receptor activation.

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“…Indeed, under physiological conditions intracellular glutathione is mainly found as GSH form at low millimolar concentrations (between 1 and 10 mM), while the content of oxidized species (oxidized GSH, GSSG and mixed disulfide, GSSR) does not exceed 1% of its total intracellular content . In its reduced form, GSH can help the body to repair oxidant damage caused by pollution, stress, infection, radiation, aging, drugs, unhealthy diet, and burns . The importance of GSH is also shown by its involvement in many cellular processes that are connected with the control of the redox status of protein thiols .…”

Section: Introductionmentioning

confidence: 99%

Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways

et al. 2018

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Glutathione is considered the major non‐protein low molecular weight modulator of redox processes and the most important thiol reducing agent of the cell. The biosynthesis of glutathione occurs in the cytosol from its constituent amino acids, but this tripeptide is also present in the most important cellular districts, such as mitochondria, nucleus, and endoplasmic reticulum, thus playing a central role in several metabolic pathways and cytoprotection mechanisms. Indeed, glutathione is involved in the modulation of various cellular processes and, not by chance, it is a ubiquitous determinant for redox signaling, xenobiotic detoxification, and regulation of cell cycle and death programs. The balance between its concentration and redox state is due to a complex series of interactions between biosynthesis, utilization, degradation, and transport. All these factors are of great importance to understand the significance of cellular redox balance and its relationship with physiological responses and pathological conditions. The purpose of this review is to give an overview on glutathione cellular compartmentalization. Information on its subcellular distribution provides a deeper understanding of glutathione‐dependent processes and reflects the importance of compartmentalization in the regulation of specific cellular pathways. © 2018 BioFactors, 45(2):152–168, 2019

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A Poloxamer-407 modified liposome encapsulating epigallocatechin-3-gallate in the presence of magnesium: Characterization and protective effect against oxidative damage

Cited by 39 publications

References 48 publications

Monoalkylated Epigallocatechin-3-gallate (C18-EGCG) as Novel Lipophilic EGCG Derivative: Characterization and Antioxidant Evaluation

Monoalkylated Epigallocatechin-3-gallate (C18-EGCG) as Novel Lipophilic EGCG Derivative: Characterization and Antioxidant Evaluation

Conformational Insight on WT- and Mutated-EGFR Receptor Activation and Inhibition by Epigallocatechin-3-Gallate: Over a Rational Basis for the Design of Selective Non-Small-Cell Lung Anticancer Agents

Glutathione compartmentalization and its role in glutathionylation and other regulatory processes of cellular pathways

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