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

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).

Cytoprotective Effect of Liposomal Puerarin on High Glucose-Induced Injury in Rat Mesangial Cells

“…In addition, the introduction of pegylated lipid can considerably change the lamellarity from 40 to 0 vol %. Similar result was also reported in our previous paper [ 19 ].…”

“…The methods for the determination of the loading efficiency and contents of puerarin in the liposomes were adapted from our previous paper [ 19 ]. The liposomal puerarin (approximately 2 mL) was placed in a sealed dialysis bag (the molecular weight cut-off MWCO = 1000).…”

“…Nowadays, the particulate-based drug delivery system (DDS) have been extensively developed to resolve the poor solubility of drug candidates [ 19 , 20 , 21 ]. Among the DDS, liposomes are fabricated by cholesterol and phospholipids which are well validated by healthcare authorities around the world.…”

Therapeutic Effects of Catechins in Less Common Neurological and Neurodegenerative Disorders

“…Catechins suppress protein expression of the toll-like receptor 4 (TLR4) and nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and induce antioxidant enzyme activities and Nrf2 mRNA levels [ 32 ]. In in-vitro neuroinflammation models, EGCG improves the production of nitric oxide and TNF-α following LPS, decreases the pro-inflammatory effect produced by LPS in a Parkinsonian syndrome rat model, and restores motor impairment [ 33 ]. EGCG intake for four months reduced β-amyloid (Aβ) plaques in the hippocampus and alleviated microglia activation in an APP/PS1 transgenic mice model.…”

Lipid-Based Drug Delivery Systems in Regenerative Medicine

“…Treatment with PLs-GDNF-MBs alleviated behavioral defects in Parkinson’s rats and increased the expressions of GDNF and Nurr1 to protect neurons. Cheng et al [ 99 ] developed epigallocatechin-3-gallate (EGCG)-loaded liposomes and demonstrated that the EGCG-loaded liposomes could activate microglia in a rat model of Parkinson’s syndrome in vivo and exert a neuroprotective effect. Kuo et al [ 100 ] prepared serotonin (SM)- and apolipoprotein E (APOE)-modified liposomes and loaded them with nerve growth factor (NGF).…”