Huperzine A ameliorates cognitive dysfunction and neuroinflammation in kainic acid-induced epileptic rats by antioxidant activity and NLRP3/caspase-1 pathway inhibition

被引：37

作者：

Mohseni-Moghaddam, Parvaneh ^{[1
]}

Sadr, Seyed Shahabeddin ^{[2
]}

Roghani, Mehrdad ^{[3
]}

Arabzadeh, Somayeh ^{[4
]}

Khamse, Safoura ^{[1
]}

Zamani, Elham ^{[1
]}

Hosseini, Marjan ^{[1
]}

Moradi, Fatemeh ^{[5
]}

机构：

[1] Univ Tehran Med Sci, Sch Med, Dept Physiol, Tehran, Iran

[2] Univ Tehran Med Sci, Neurosci Inst, Electrophysiol Res Ctr, Tehran, Iran

[3] Shahed Univ, Neurophysiol Res Ctr, Tehran, Iran

[4] Taha Inst Higher Educ, Sch Biol, Tehran, Iran

[5] Zanjan Univ Med Sci, Sch Med, Dept Physiol, Zanjan, Iran

来源：

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY | 2019年 / 46卷 / 04期

关键词：

acetylcholinesterase; cognitive dysfunction; huperzine A; inflammasome; oxidative stress; temporal lobe epilepsy; TEMPORAL-LOBE EPILEPSY; NLRP3 INFLAMMASOME ACTIVATION; OXIDATIVE STRESS; MODEL; RECOGNITION; SEIZURE;

D O I：

10.1111/1440-1681.13064

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Temporal lobe epilepsy (TLE) is one of the most prevalent types of epilepsy in human. Huperzine A (Hup-A) has been reported to possess antioxidative and anti-inflammatory properties; however, its role in TLE induced by kainic acid has not been determined. The current study investigated the protective effects of Hup-A (0.1 mg/kg) in kainic acid-induced model of TLE in the rat. In the current study, it was found that Hup-A significantly prevented the seizure intensity and learning and memory deterioration which was assessed by Morris water maze (MWM) and novel object recognition task (NOR). Additionally, Hup-A inhibited oxidative stress, inflammation, and acetylcholinesterase activity (AChE). In addition, catalase and superoxide dismutase (SOD) activities increased after Hup-A treatment, while malondialdehyde (MDA) and nitrite levels significantly reduced. Regarding inflammation, this drug decreased kainic acid-induced NLRP3 expression in microglial cells and caspase-1 activity in hippocampal tissue, possibly through diminishing oxidative stress. Taken together, our data showed that Hup-A could be a potential protective substance to ameliorate seizure severity and some memory deficits related to epilepsy via attenuating neuroinflammation and protection of neurons.

引用

页码：360 / 372

页数：13

共 59 条

[11] Huperzine A as a neuroprotective and antiepileptic drug: a review of preclinical research [J].

Damar, U. ;

Gersner, R. ;

Johnstone, J. T. ;

Schachter, S. ;

Rotenberg, A. .

EXPERT REVIEW OF NEUROTHERAPEUTICS, 2016, 16 (06) :671-680

[12] A NEW AND RAPID COLORIMETRIC DETERMINATION OF ACETYLCHOLINESTERASE ACTIVITY [J].

ELLMAN, GL ;

COURTNEY, KD ;

ANDRES, V ;

FEATHERSTONE, RM .

BIOCHEMICAL PHARMACOLOGY, 1961, 7 (02) :88-&

[13] Long-Term Valproate Treatment Increases Brain Neuropeptide Y Expression and Decreases Seizure Expression in a Genetic Rat Model of Absence Epilepsy [J].

Elms, Johanna ;

Powell, Kim L. ;

van Raay, Leena ;

Dedeurwaerdere, Stefanie ;

O'Brien, Terence J. ;

Morris, Margaret J. .

PLOS ONE, 2013, 8 (09)

[14] The Neuroprotective Effect of Curcumin and Nigella sativa Oil Against Oxidative Stress in the Pilocarpine Model of Epilepsy: A Comparison with Valproate [J].

Ezz, Heba S. Aboul ;

Khadrawy, Yasser A. ;

Noor, Neveen A. .

NEUROCHEMICAL RESEARCH, 2011, 36 (11) :2195-2204

[15] Huperzine A prophylaxis against pentylenetetrazole-induced seizures in rats is associated with increased cortical inhibition [J].

Gersner, R. ;

Ekstein, D. ;

Dhamne, S. C. ;

Schachter, S. C. ;

Rotenberg, A. .

EPILEPSY RESEARCH, 2015, 117 :97-103

[16] Acetylcholinesterase loosens the brain's cholinergic anti-inflammatory response and promotes epileptogenesis [J].

Gnatek, Yehudit ;

Zimmerman, Gabriel ;

Goll, Yael ;

Najami, Naim ;

Soreq, Hermona ;

Friedman, Alon .

FRONTIERS IN MOLECULAR NEUROSCIENCE, 2012, 5

[17] NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes [J].

Gustin, Audrey ;

Kirchmeyer, Melanie ;

Koncina, Eric ;

Felten, Paul ;

Losciuto, Sophie ;

Heurtaux, Tony ;

Tardivel, Aubry ;

Heuschling, Paul ;

Dostert, Catherine .

PLOS ONE, 2015, 10 (06)

[18] Modulatory mechanisms controlling the NLRP3 inflammasome in inflammation: recent developments [J].

Haneklaus, Moritz ;

O'Neill, Luke A. J. ;

Coll, Rebecca C. .

CURRENT OPINION IN IMMUNOLOGY, 2013, 25 (01) :40-45

[19] The complexity of NF-κB signaling in inflammation and cancer [J].

Hoesel, Bastian ;

Schmid, Johannes A. .

MOLECULAR CANCER, 2013, 12

[20] Valproate pretreatment protects pancreatic β-cells from palmitate-induced ER stress and apoptosis by inhibiting glycogen synthase kinase-3β [J].

Huang, Shan ;

Zhu, Minghui ;

Wu, Wei ;

Rashid, Abid ;

Liang, Yan ;

Hou, Ling ;

Ning, Qin ;

Luo, Xiaoping .

JOURNAL OF BIOMEDICAL SCIENCE, 2014, 21

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