Epigallocatechin-3-Gallate-Loaded Liposomes Favor Anti-Inflammation of Microglia Cells and Promote Neuroprotection.

Chun-Yuan Cheng,Xiao-Yu Wu,Che-Wei Chao,Ruei-Siang Yu,Ting-Yu Chin,Ming Fa Hsieh,Lassina Barro,Shang-Ting Tsai,Tai-Wei Feng

doi:10.3390/ijms22063037

Abstract

Microglia-mediated neuroinflammation is recognized to mainly contribute to the progression of neurodegenerative diseases. Epigallocatechin-3-gallate (EGCG), known as a natural antioxidant in green tea, can inhibit microglia-mediated inflammation and protect neurons but has disadvantages such as high instability and low bioavailability. We developed an EGCG liposomal formulation to improve its bioavailability and evaluated the neuroprotective activity in in vitro and in vivo neuroinflammation models. EGCG-loaded liposomes have been prepared from phosphatidylcholine (PC) or phosphatidylserine (PS) coated with or without vitamin E (VE) by hydration and membrane extrusion method. The anti-inflammatory effect has been evaluated against lipopolysaccharide (LPS)-induced BV-2 microglial cells activation and the inflammation in the substantia nigra of Sprague Dawley rats. In the cellular inflammation model, murine BV-2 microglial cells changed their morphology from normal spheroid to activated spindle shape after 24 h of induction of LPS. In the in vitro free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, EGCG scavenged 80% of DPPH within 3 min. EGCG-loaded liposomes could be phagocytized by BV-2 cells after 1 h of cell culture from cell uptake experiments. EGCG-loaded liposomes improved the production of BV-2 microglia-derived nitric oxide and TNF-α following LPS. In the in vivo Parkinsonian syndrome rat model, simultaneous intra-nigral injection of EGCG-loaded liposomes attenuated LPS-induced pro-inflammatory cytokines and restored motor impairment. We demonstrated that EGCG-loaded liposomes exert a neuroprotective effect by modulating microglia activation. EGCG extracted from green tea and loaded liposomes could be a valuable candidate for disease-modifying therapy for Parkinson’s disease (PD).

Highlights

When the nervous system is damaged or infected, microglia cells are activated and transformed to be branched, resulting in excessive expression of a large amount of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin 6 (IL-6), and inflammatory mediators such as nitric oxide (NO) and reactive oxygen species (ROS)
This study indicates that improvement of limb coordination and reduction of neuroinflammation in LPS-induced Parkinsonian syndrome is caused by locally administering EGCG-loaded liposomes but not by increasing expression of brain-derived neurotrophic factor (BDNF)
To improve the low oral bioavailability of catechins, EGCG was loaded in liposomes in this study

Summary

Introduction

When the nervous system is damaged or infected, microglia cells are activated and transformed to be branched, resulting in excessive expression of a large amount of proinflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin 6 (IL-6), and inflammatory mediators such as nitric oxide (NO) and reactive oxygen species (ROS). It is recently found that in the brain of patients with neurodegenerative diseases such as Parkinson s disease (PD), Alzheimer s disease, Huntington s disease, and Creutzfeldt-Jakob disease, large amounts of microglia cells are activated and over-expressed [1,2,3]. The inflammatory mediators resulting, such as TNF-α, IL-1β, IL-6, NO, and ROS, are found in the striatum of the brain [1,4,5,6,7]. The degradation of dopaminergic neurons can be regulated by microglia cells [8]

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Conclusion