Lipid rafts as potential mechanistic targets underlying the pleiotropic actions of polyphenols

Wang, Ruifeng; Zhu, Wei; Peng, Jinming; Li, Kaikai; Li, Chunmei

doi:10.1080/10408398.2020.1815171

Cited by 11 publications

(11 citation statements)

References 117 publications

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“…Phenolic compounds Artepillin C [460], Chlorogenic acid and Isochlorogenic acid [461], Proanthocyanidins [462,463], Oleuropein aglycone [464], Other [465][466][467][468][469] The orientation and location of drug molecules in lipid membranes is clearly only the beginning of our story. Once molecules enter a biomembrane they can do three different things: (1) pass out of the membrane again, possibly on the other side, the membrane merely forming a biological barrier on their way to their eventual destination, (2) act collectively to instigate large scale alteration or even disruption of the membrane structure, or (3) interact with proteins that are associated with the membrane.…”

Section: Antioxidantsmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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We review the use of molecular dynamics (MD) simulation as a drug design tool in the context of the role that the lipid membrane can play in drug action, i.e., the interaction between candidate drug molecules and lipid membranes. In the standard “lock and key” paradigm, only the interaction between the drug and a specific active site of a specific protein is considered; the environment in which the drug acts is, from a biophysical perspective, far more complex than this. The possible mechanisms though which a drug can be designed to tinker with physiological processes are significantly broader than merely fitting to a single active site of a single protein. In this paper, we focus on the role of the lipid membrane, arguably the most important element outside the proteins themselves, as a case study. We discuss work that has been carried out, using MD simulation, concerning the transfection of drugs through membranes that act as biological barriers in the path of the drugs, the behavior of drug molecules within membranes, how their collective behavior can affect the structure and properties of the membrane and, finally, the role lipid membranes, to which the vast majority of drug target proteins are associated, can play in mediating the interaction between drug and target protein. This review paper is the second in a two-part series covering MD simulation as a tool in pharmaceutical research; both are designed as pedagogical review papers aimed at both pharmaceutical scientists interested in exploring how the tool of MD simulation can be applied to their research and computational scientists interested in exploring the possibility of a pharmaceutical context for their research.

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Section: Antioxidantsmentioning

confidence: 99%

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

2021

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“…For example, epigallocatechin gallate (EGCG) inhibited the activity of epidermal growth factor receptor by reducing its localization in lipid rafts and therefore blocked the progression of colon cancer cells. 24 Docosahexanoic acid (DHA) was found to show an antidepressant effect by decreasing the localization of Gs α protein in lipid rafts and enhancing the activity of adenylate cyclase. 32 The peptides QVPLW and LCAY, with a certain degree of hydrophobicity, may interact with cell membrane lipids or partition into the membrane, thereby facilitating the translocation of ACE into nonlipid rafts.…”

Section: ■ Discussionmentioning

confidence: 99%

“…Moreover, the difference in the interaction between peptides and the cell membrane may be related to the structure and sequence of peptides and cell membrane lipid composition. 24,42 In summary, this article provides insights into the ACE inhibitory mechanism of egg white peptides. Peptides can indirectly inhibit ACE activity by regulating the localization of ACE in the cell membrane and cell membrane properties.…”

Section: ■ Discussionmentioning

confidence: 99%

“…The methods currently used to study the association between membrane proteins and lipid rafts are largely based on the isolation of lipid rafts and the use of immunoblotting tools combined with confocal microscopic imaging, which enables the evaluation and verification of protein localization in the cell membrane in a multifaceted manner. , Methyl-β-cyclodextrin (MβCD) is widely used for evaluating the relationship between lipid rafts and membrane proteins as it depletes cholesterol in lipid rafts and perturbs the stability and functions of lipid rafts . Here, MβCD was used to study the correlation between the activities of ACE and lipid rafts.…”

Section: Introductionmentioning

confidence: 99%

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Egg White-Derived Peptides QVPLW and LCAY Inhibit the Activity of Angiotensin I-Converting Enzyme in Human Umbilical Vein Endothelial Cells by Suppressing Its Recruitment into Lipid Rafts

Jiang

Wang

Liu

et al. 2021

J. Agric. Food Chem.

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As a membrane protein, the activity of angiotensin I-converting enzyme (ACE) can be modulated via regulation of its localization in the cell membrane with food-derived peptides. This study aimed to explore the effect of egg white peptides on the cell membrane localization and activity of ACE in human umbilical vein endothelial cells. ACE activity was found to be related to lipid rafts by using methyl-β-cyclodextrin (MβCD). QVPLW and LCAY can inhibit ACE activity by preventing ACE recruitment into lipid rafts, with in situ IC50 values of 238.46 ± 11.35 μM and 31.55 ± 2.64 μM in the control groups, as well as 45.43 ± 6.15 μM and 34.63 ± 1.59 μM in the MβCD groups, respectively. QVPLW and LCAY may alter the cell membrane properties, including the fluidity, potential, and permeability, and eventually promote the transposition of ACE.

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“…The selective effect on LOX-1 laterally segregation is not limited to lactucopicrin, as other phytochemicals (e.g., epigallocatechin gallate, quercetin, and resveratrol) have been documented to affect different molecules laterally segregation across lipid rafts and non-lipid rafts. [25,26] Nevertheless, the exact mechanism for the lactucopicrin effect on LOX-1 laterally segregation in the cell membrane is currently unknown.…”

Section: Discussionmentioning

confidence: 99%

Terpene Lactucopicrin Limits Macrophage Foam Cell Formation by a Reduction of Lectin‐Like Oxidized Low‐Density Lipoprotein Receptor‐1 in Lipid Rafts

Liu

Zhang

et al. 2021

Molecular Nutrition Food Res

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Scope: Sustained inflammation promotes macrophage foam cell formation by promoting cholesterol influx and impairing cholesterol efflux. Terpene lactucopicrin, affluent in vegetables of the Asteraceae family (e.g., chicory, curly escarole, and lettuce) can inhibit atherogenesis in mice. However, it remains unknown whether and how lactucopicrin regulates macrophage foam cell formation. Methods and Results: Lactucopicrin at physiologically reachable concentrations inhibits oxidized low-density lipoprotein (oxLDL)-induced foam cell formation in inflammatory mouse bone marrow derived macrophages established by 50 pg mL -1 of LPS, reachable level in patients with metabolic endotoxemia. This effect is not due to modulation of cholesterol efflux, but reliant on a reduction in lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)-mediated cholesterol influx. Mechanistically, lactucopicrin does not affect LOX-1 expression, cellular oxidative stress, and exocytosis, known mechanisms regulating LOX-1 function in cholesterol influx. Strikingly, lactucopicrin selectively decreases LOX-1 content in lipid rafts, an effect responsible for the lactucopicrin effect on cholesterol influx. Moreover, ApoE -/mice fed a high fat diet supplemented with lactucopicrin for 12 weeks display fewer macrophage foam cells within atherosclerotic plaques relative to the control mice. Conclusion: Lactucopicrin limits macrophage foam cell formation through a reduction of LOX-1 distribution in lipid rafts, thus contributing to its atheroprotective effect.

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Lipid rafts as potential mechanistic targets underlying the pleiotropic actions of polyphenols

Cited by 11 publications

References 117 publications

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Mechanistic Understanding from Molecular Dynamics in Pharmaceutical Research 2: Lipid Membrane in Drug Design

Egg White-Derived Peptides QVPLW and LCAY Inhibit the Activity of Angiotensin I-Converting Enzyme in Human Umbilical Vein Endothelial Cells by Suppressing Its Recruitment into Lipid Rafts

Terpene Lactucopicrin Limits Macrophage Foam Cell Formation by a Reduction of Lectin‐Like Oxidized Low‐Density Lipoprotein Receptor‐1 in Lipid Rafts

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