Understanding Interactions of Curcumin with Lipid Bilayers: A Coarse-Grained Molecular Dynamics Study

Ileri-Ercan, Nazar

doi:10.1021/acs.jcim.9b00650

Cited by 18 publications

(16 citation statements)

References 76 publications

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“…82 The mechanistic details that underlie curcumin-membrane interactions are provided elsewhere. 83 − 85 This fraction of blood is not included in the plasma analysis, which does not apply to the cell-unassociated nanoparticulate curcumin that remains in the plasma fraction during sample processing. Another possibility is that hepatic and renal clearance already contribute to the concentration decline in the distribution phase and that the clearance favors free curcumin due to steric factors in terms of particle size relative to the size of the endothelial fenestrations in the kidneys and liver.…”

Section: Nanoformulations Improve Multiple Curcumin Pharmacokinetics ...mentioning

confidence: 99%

Utility of Intravenous Curcumin Nanodelivery Systems for Improving In Vivo Pharmacokinetics and Anticancer Pharmacodynamics

et al. 2022

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Curcumin nanoformulations for intravenous injection have been developed to offset poor absorption, biotransformation, degradation, and excessive clearance associated with parenteral delivery. This review investigates (1) whether intravenous nanoformulations improve curcumin pharmacokinetics (PK) and (2) whether improved PK yields greater therapeutic efficacy. Standard PK parameters (measured maximum concentration [ C max ], area under the curve [AUC], distribution volume [ V d ], and clearance [CL]) of intravenously administered free curcumin in mice and rats were sourced from literature and compared to curcumin formulated in nanoparticles, micelles, and liposomes. The studies that also featured analysis of pharmacodynamics (PD) in murine cancer models were used to determine whether improved PK of nanoencapsulated curcumin resulted in improved PD. The distribution and clearance of free and nanoformulated curcumin were very fast, typically accounting for >80% curcumin elimination from plasma within 60 min. Case-matched analysis demonstrated that curcumin nanoencapsulation generally improved curcumin PK in terms of measured C max ( n = 27) and AUC ( n = 33), and to a lesser extent V d and CL. However, when the data were unpaired and clustered for comparative analysis, only 5 out of the 12 analyzed nanoformulations maintained a higher relative curcumin concentration in plasma over time compared to free curcumin. Quantitative analysis of the mean plasma concentration of free curcumin versus nanoformulated curcumin did not reveal an overall marked improvement in curcumin PK. No correlation was found between PK and PD, suggesting that augmentation of the systemic presence of curcumin does not necessarily lead to greater therapeutic efficacy.

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Section: Nanoformulations Improve Multiple Curcumin Pharmacokinetics ...mentioning

confidence: 99%

Utility of Intravenous Curcumin Nanodelivery Systems for Improving In Vivo Pharmacokinetics and Anticancer Pharmacodynamics

et al. 2022

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“…Cellular membranes consist of various lipids in diverse amounts and proportions. Increasing evidence indicates that membrane lipid composition is relevant to multiple functions in physiology. − Therefore, it is meaningful to understand how lipid composition is translated into functions.…”

Section: Introductionmentioning

confidence: 99%

In Silico Study of Membrane Lipid Composition Regulating Conformation and Hydration of Influenza Virus B M2 Channel

Zhang

Zheng

2020

J. Chem. Inf. Model.

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The proton conduction of transmembrane influenza virus B M2 (BM2) proton channel is possibly mediated by the membrane environment, but the detailed molecular mechanism is challenging to determine. In this work, how membrane lipid composition regulates the conformation and hydration of BM2 channel is elucidated in silico. The appearance of several important hydrogen-bond networks has been discovered, as the addition of negatively charged lipid palmitoyloleoyl phosphatidylglycerol (POPG) and cholesterol reduces membrane fluidity and augments membrane rigidity. A more rigid membrane environment is beneficial to expand the channel, allow more water to enter the channel, promote channel hydration, and then even affect the proton conduction facilitated by the hydrated channel. Thus, membrane environment could be identified as an important influence factor of conformation and hydration of BM2. These findings can provide a unique perspective for understanding the mechanism of membrane lipid composition regulating conformation and hydration of BM2 and have important significance to the further study of anti-influenza virus B drugs.

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“…Preliminary experiments suggest that curcumin does not bind in the two known binding pockets: in the pore [ 15 ], or along the cytoplasmic surface of the protein [ 16 , 17 , 18 ] (see S2 Fig ). In addition, there are indications that the different lipid compositions of mammalian, yeast and bacterial membranes determine curcumin distribution within the lipid bilayer and thus the alteration of membrane properties [ 24 ], which could conceivably partially explain bacterial-membrane specificity for altering membrane-protein function. Curcumin is also thought to thin the membrane [ 25 ]; and there are indications that MscL may be somewhat more sensitive to membrane thinning than our control channel, MscS [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

Curcumin activation of a bacterial mechanosensitive channel underlies its membrane permeability and adjuvant properties

2021

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Curcumin, a natural compound isolated from the rhizome of turmeric, has been shown to have antibacterial properties. It has several physiological effects on bacteria including an apoptosis-like response involving RecA, membrane permeabilization, inhibiting septation, and it can also work synergistically with other antibiotics. The mechanism by which curcumin permeabilizes the bacterial membrane has been unclear. Most bacterial species contain a Mechanosensitive channel of large conductance, MscL, which serves the function of a biological emergency release valve; these large-pore channels open in response to membrane tension from osmotic shifts and, to avoid cell lysis, allow the release of solutes from the cytoplasm. Here we show that the MscL channel underlies the membrane permeabilization by curcumin as well as its synergistic properties with other antibiotics, by allowing access of antibiotics to the cytoplasm; MscL also appears to have an inhibitory role in septation, which is enhanced when activated by curcumin.

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Understanding Interactions of Curcumin with Lipid Bilayers: A Coarse-Grained Molecular Dynamics Study

Cited by 18 publications

References 76 publications

Utility of Intravenous Curcumin Nanodelivery Systems for Improving In Vivo Pharmacokinetics and Anticancer Pharmacodynamics

Utility of Intravenous Curcumin Nanodelivery Systems for Improving In Vivo Pharmacokinetics and Anticancer Pharmacodynamics

In Silico Study of Membrane Lipid Composition Regulating Conformation and Hydration of Influenza Virus B M2 Channel

Curcumin activation of a bacterial mechanosensitive channel underlies its membrane permeability and adjuvant properties

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