Epigallocatechin-3-Gallate and PEDF 335 Peptide, 67LR Activators, Attenuate Vasogenic Edema, and Astroglial Degeneration Following Status Epilepticus

Abstract

Non-integrin 67-kDa laminin receptor (67LR) is involved in cell adherence to the basement membrane, and it regulates the interactions between laminin and other receptors. The dysfunction of 67LR leads to serum extravasation via blood-brain barrier (BBB) disruption. Polyphenol (–)-epigallocatechin-3-O-gallate (EGCG) and pigment epithelium-derived factor (PEDF) bind to 67LR and inhibit neovascularization. Therefore, in the present study, we investigated the effects of EGCG and NU335, a PEDF-derive peptide, on BBB integrity and their possible underlying mechanisms against vasogenic edema formation induced by status epilepticus (SE, a prolonged seizure activity). Following SE, both EGCG and NU335 attenuated serum extravasation and astroglial degeneration in the rat piriform cortex (PC). Both EGCG and NU335 reversely regulated phosphatidylinositol 3 kinase (PI3K)/AKT–eNOS (endothelial nitric oxide synthase) mediated BBB permeability and aquaporin 4 (AQP4) expression in endothelial cells and astrocytes through the p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways, respectively. Furthermore, EGCG and NU335 decreased p47Phox (a nicotinamide adenine dinucleotide phosphate oxidase subunit) expression in astrocytes under physiological and post-SE conditions. Therefore, we suggest that EGCG and PEDF derivatives may activate 67LR and its downstream effectors, and they may be considerable anti-vasogenic edema agents.

Biodegradable nanoparticles for the treatment of epilepsy: From current advances to future challenges

“…Furthermore, Cano et al 45 developed PNP capable of encapsulating epigallocatechin‐3‐gallate (EGCG), one of the most abundant catechins in tea. EGCG is known to reduce seizure episodes, but the exact mechanism is not yet fully elucidated 38,46 . EGCG PNP were developed using a PLGA matrix along with polyethylene glycol (PEG) functionalization.…”

“…EGCG is known to reduce seizure episodes, but the exact mechanism is not yet fully elucidated. 38 , 46 EGCG PNP were developed using a PLGA matrix along with polyethylene glycol (PEG) functionalization. EGCG PNP were assessed in an in vivo study using the kainic acid‐induced mouse temporal lobe epilepsy model showing interesting results.…”

A comprehensive review of the influence of Epigallocatechin gallate on Sjögren's syndrome associated molecular regulators of exocytosis (Review)

“…EGCG significantly inhibits the expression levels of AQP4 in a traumatic brain injury model ( 113 ), as well as a rat spinal injury model ( 114 ), reducing the associated oedema. EGCG prevention of vasogenic oedema associated with status epilepticus was also mediated through regulation of AQP4 expression, however this time via its upregulation ( 115 ).…”

Intra-Articular Injection of (−)-Epigallocatechin 3-Gallate (EGCG) Ameliorates Cartilage Degeneration in Guinea Pigs with Spontaneous Osteoarthritis

“…(−)-Epigallocatechin 3-gallate (EGCG), the major bioactive component of green tea catechins, has gained interest in OA research because of its potent anti-inflammatory and antioxidative properties [ 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ]. The chondroprotective effect of EGCG has been widely investigated using human articular chondrocytes [ 22 , 23 , 24 ], animal articular chondrocytes [ 25 , 26 ], bovine cartilage explants [ 27 ], and surgically induced OA animal models [ 28 , 29 , 30 ].…”