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Epigallocatechin-3-gallate: a useful, effective and safe clinical approach for targeted prevention and individualised treatment of neurological diseases?

ABSTRACT: Neurodegenerative disorders show an increasing prevalence in a number of highly developed countries. Often, these diseases require life-long treatment mostly with drugs which are costly and mostly accompanied by more or less serious side-effects. Their heterogeneous manifestation, severity and outcome pose the need for individualised treatment options. There is an intensive search for new strategies not only for treating but also for preventing these diseases. Green tea and green tea extracts seem to be such a promising and safe alternative. However, data regarding the beneficial effects and possible underlying mechanism, specifically in clinical trials, are rare and rather controversial or non-conclusive. This review outlines the existing evidence from preclinical studies (cell and tissue cultures and animal models) and clinical trials regarding preventive and therapeutic effects of epigallcatechin-3-gallate in neurodegenerative diseases and considers antioxidative vs. pro-oxidative properties of the tea catechin important for dosage recommendations.

SUBMITTER: Mahler A

PROVIDER: S-EPMC3585739 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Epigallocatechin-3-gallate: a useful, effective and safe clinical approach for targeted prevention and individualised treatment of neurological diseases?

Mähler Anja A Mandel Silvia S Lorenz Mario M Ruegg Urs U Wanker Erich E EE Boschmann Michael M Paul Friedemann F

The EPMA journal 20130218 1

Neurodegenerative disorders show an increasing prevalence in a number of highly developed countries. Often, these diseases require life-long treatment mostly with drugs which are costly and mostly accompanied by more or less serious side-effects. Their heterogeneous manifestation, severity and outcome pose the need for individualised treatment options. There is an intensive search for new strategies not only for treating but also for preventing these diseases. Green tea and green tea extracts se ...[more]

PMID: 23418936

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Project description:Intimal macrophages play a critical role in atherosclerotic lesion initiation and progression by taking up oxidized low-density lipoprotein (oxLDL) and promoting inflammatory process. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine (KOdiA-PC), a major type of oxidized phosphatidylcholines (PC) found on oxLDL, has a high binding affinity to the macrophage scavenger receptor CD36 and participates in CD36-mediated recognition and uptake of oxLDL by intimal macrophages. We successfully synthesized epigallocatechin gallate (EGCG)-loaded nanoparticles (Enano), which were composed of EGCG, PC, (+) alpha-tocopherol acetate, and surfactant. We also incorporated KOdiA-PC on the surface of Enano to make ligand-coated Enano (L-Enano) to target intimal macrophages. The objectives of this study were to determine the anti-atherogenic effects of Enano and L-Enano in LDL receptor null (LDLr-/-) mice. Our in vitro data demonstrated that L-Enano had a higher binding affinity to mouse peritoneal macrophages than Enano. This high binding affinity was diminished by CD36 antibodies or knockdown of the CD36 receptor in mouse peritoneal macrophages, confirming the specific binding of L-Enano to the macrophage CD36 receptor. LDLr-/- mice were randomly divided to six groups and received weekly tail vein injection with PBS, EGCG, void nanoparticles (Vnano), Enano, ligand-coated Vnano (L-Vnano), or L-Enano once per week for 22?weeks. The dose of EGCG was 25?mg per kg body weight. L-Enano at 20??g/mL significantly decreased production of monocyte chemoattractant protein-1, tumor necrosis factor alpha, and interleukin-6 from mouse macrophages, while having no effect on their plasma levels compared to the PBS control. There were no significant differences in blood lipid profiles among six treatment groups. Mice treated with L-Enano also had significantly smaller lesion surface areas on aortic arches compared to the PBS control. Liver EGCG content was decreased by treatments in the order of EGCG>Enano>L-Enano. Native EGCG had inhibitory effects on liver and body fat accumulation. This molecular target approach signals an important step towards inhibiting atherosclerosis development via targeted delivery of bioactive compounds to intimal macrophages.

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Epigallocatechin-3-gallate: a useful, effective and safe clinical approach for targeted prevention and individualised treatment of neurological diseases?

Publications

Epigallocatechin-3-gallate: a useful, effective and safe clinical approach for targeted prevention and individualised treatment of neurological diseases?

Similar Datasets

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