1. Academic Validation
  2. Gentiopicroside alleviated epileptogenesis in immature rats through inactivation of NLRP3 inflammasome by inhibiting P2X7R expression

Gentiopicroside alleviated epileptogenesis in immature rats through inactivation of NLRP3 inflammasome by inhibiting P2X7R expression

  • Int J Dev Neurosci. 2022 Nov 7. doi: 10.1002/jdn.10237.
Weilong Yang 1 2 Lin Ma 3 Siying Xu 1 Ping Zheng 3 Juan Du 3 Jing Wu 4 Jianqiang Yu 3 Tao Sun 5
Affiliations

Affiliations

  • 1 School of Clinical Medicine, Ningxia Medical University, Yinchuan, Ningxia, China.
  • 2 Department of Neurosurgery, The First Affiliated Hospital of Xinxiang Medical University, Wei Hui, Henan, China.
  • 3 Department of Pharmacology, Ningxia Medical University, Yinchuan, Ningxia, China.
  • 4 Laboratory Animal Centre, Ningxia Medical University, Yinchuan, Ningxia, China.
  • 5 Ningxia Key Laboratory of Craniocerebral Diseases of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, Ningxia, China.
Abstract

Objectives: This study aimed to elucidate the effects of Gentiopicroside (Gent) on epileptogenesis and underlying mechanisms.

Methods: The status epilepticus (SE) model was established by intraperitoneal (i.p.) injection of lithium chloride (127mg/kg) and pilocarpine (50mg/kg) in immature rats. HAPI microglial cellular inflammation model was induced by lipopolysaccharide (LPS, 1μg/mL) and adenosine triphosphate (ATP, 5mM). The differential concentrations of Gent were used to pretreat animal (200, 400, and 800mg/kg) and model cells (50, 100, and 200μM). Epileptic discharges were assessed by electroencephalography (EEG) and Racine scale. Changes in spatial memory function were measured using the Morris water maze task test. Nissl and FJB staining were employed to assess the damage to hippocampus tissues. ELISA was used to detect the production of IL-1β, IL-18, and TNF-α. The expressions of P2X7R and NLRP3 were detected by q-PCR, immunofluorescence staining, and Western blot, and cell viability was determined by cell counting kit-8 (CCK-8).

Results: Lithium chloride and pilocarpine (LICL-PILO) induced abnormal EEG activities, behavioral alterations, brain damage, and inflammatory responses in immature rats. However, Gent pretreatment significantly reduced the neuronal damage and spatial memory dysfunction induced by LICL-PILO. Additionally, Gent suppressed the production of inflammatory cytokines and inhibited the expression of P2X7R, NLRP3, ASC, and Caspase-1 in LPS/ATP-induced HAPI microglial cells.

Discussion: Gent intervention could improve epileptogenesis in immature rats partially due to suppressing P2X7R and NLRP3 inflammasome.

Keywords

Gentiopicroside; NLRP3 inflammasome; P2X7R; Pediatric epilepsy; inflammation; status epilepticus.

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