11-Keto-β-Boswellic Acid Attenuates Glutamate Release and Kainic Acid-Induced Excitotoxicity in the Rat Hippocampus

Cheng Wei Lu; Tzu Yu Lin; Su Jane Wang

doi:10.1055/a-1107-9337

Planta Medica, Inhaltsverzeichnis

Planta Med 2020; 86(06): 434-441
DOI: 10.1055/a-1107-9337

Biological and Pharmacological Activity

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

11-Keto-β-Boswellic Acid Attenuates Glutamate Release and Kainic Acid-Induced Excitotoxicity in the Rat Hippocampus

Autoren

Cheng Wei Lu

¹Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City, Taiwan

³Department of Mechanical Engineering, Yuan Ze University, Taoyuan City, Taiwan
Tzu Yu Lin

¹Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City, Taiwan

³Department of Mechanical Engineering, Yuan Ze University, Taoyuan City, Taiwan
Su Jane Wang

²School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan

⁴Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City, Taiwan

Abstract

Excessive glutamate concentration induces neuronal death in acute brain injuries and chronic neurodegenerative diseases. Natural compounds from medicinal plants have attracted considerable attention for their use in the prevention and treatment of neurological disorders. 11-Keto-β-boswellic acid, a triterpenoid found in the medicinal plant Boswellia serrata, has neuroprotective potential. The present study investigated the effect of 11-keto-β-boswellic acid on glutamate release in vitro and kainic acid-induced glutamate excitotoxicity in vivo in the rat hippocampus. In rat hippocampal nerve terminals (synaptosomes), 11-keto-β-boswellic acid dose-dependently inhibited 4-aminopyridine-stimulated glutamate release. This effect was dependent on extracellular calcium, persisted in the presence of the glutamate transporter inhibitor DL-threo-β-benzyloxyaspartate, and was blocked by the vesicular transporter inhibitor bafilomycin A1. In addition, 11-keto-β-boswellic acid reduced the 4-aminopyridine-induced increase in intrasynaptosomal Ca²⁺ levels. The N- and P/Q-type channel blocker ω-conotoxin MVIIC and the protein kinase A inhibitor H89 significantly suppressed the 11-keto-β-boswellic acid-mediated inhibition of glutamate release, whereas the intracellular Ca²⁺-releasing inhibitors dantrolene, CGP37157, and xestospongin C, mitogen-activated protein kinase inhibitor PD98059, as well as protein kinase C inhibitor calphostin C had no effect. In a rat model of excitotoxicity induced by intraperitoneal kainic acid injection (15 mg/kg), intraperitoneal 11-keto-β-boswellic acid administration (10 or 50 mg/kg) 30 min before kainic acid injection considerably ameliorated kainic acid-induced glutamate concentration elevation and CA3 neuronal death. These data suggested that 11-keto-β-boswellic acid inhibits glutamate release from the rat hippocampal synaptosomes by suppressing N- and P/Q-type Ca²⁺ channels and protein kinase A activity, as well as exerts protective effects against kainic acid-induced excitotoxicity in vivo.

Key words

Burseraceae - Boswellia serrata - KBA - presynaptic glutamate release - kainic acid - neuroprotection - hippocampus

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Referenzen

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