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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

Cheng Wei Lu
1   Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City, Taiwan
3   Department of Mechanical Engineering, Yuan Ze University, Taoyuan City, Taiwan
,
Tzu Yu Lin
1   Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City, Taiwan
3   Department of Mechanical Engineering, Yuan Ze University, Taoyuan City, Taiwan
,
Su Jane Wang
2   School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan
4   Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan City, Taiwan
› Author AffiliationsSupported by: the Ministry of Science and Technology Taiwan MOST 107-2314-B-418-005; MOST 106-2320-B-030-002
Further Information

Publication History

received 29 October 2019
revised 20 January 2020

accepted 28 January 2020

Publication Date:
25 February 2020 (online)

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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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