.png){kind=icon}
.png){kind=icon}
Return
Phlorizin Inhibits Glutamate Release from Cortical Synaptosomes and Protects against Kainic Acid-Induced Excitotoxicity in Rats
.png){kind=icon}
PRE
AI
C
T
K
M
Y
S
DOI：10.1021/acs.jafc.5c11994.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
This research investigates how phlorizin, a plant-derived dihydrochalcone, modulates glutamate release in synaptosomes and exerts neuroprotective effects in a rat model of kainic acid (KA)-induced excitotoxicity. In rat cortical synaptosomes, phlorizin concentration-dependently inhibited evoked glutamate release (IC50 = 14.4 μM). This effect was abolished under calcium-free conditions or by blockade of P/Q type but not N type Ca2+ channels. In vivo, oral phlorizin pretreatment (100 mg/kg/day, 7 days) attenuated KA-induced seizures and neurodegeneration, restored NeuN and GAP-43 expression, and normalized cortical glutamate homeostasis by regulating GLT-1, glutamine synthetase, SNAT1/3, glutaminase, and VGLUT1. It shifted NMDA receptor subunit composition toward a neuroprotective profile (increasing GluN2A/GluN2B ratio) and suppressed astrocytic IL-1β/IL-1R1/Src signaling. Furthermore, phlorizin preserved blood brain barrier integrity by increasing ZO-1 and reducing albumin extravasation and MMP-9. These results demonstrate that phlorizin exerts multifaceted neuroprotection by inhibiting synaptic glutamate release, modulating glutamate homeostasis, and suppressing neuroinflammation and barrier disruption.
Keywords:
Monomers
Nervous system diseases
Peptides and proteins
Pretreatment
Rodent models
phlorizin
glutamate
synaptosome
glutamate excitotoxicity
kainic acid
cortex
Journal
IF:
6.2
Papers:
4.5W
Citations:
15.3W
Organization
Cited Papers