Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City, Taiwan.
Department of Mechanical Engineering, Yuan Ze University, Taoyuan City, Taiwan.
Planta Med. 2020 Apr;86(6):434-441. doi: 10.1055/a-1107-9337. Epub 2020 Feb 25.
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--boswellic acid, a triterpenoid found in the medicinal plant , has neuroprotective potential. The present study investigated the effect of 11-keto--boswellic acid on glutamate release and kainic acid-induced glutamate excitotoxicity in the rat hippocampus. In rat hippocampal nerve terminals (synaptosomes), 11-keto--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--benzyloxyaspartate, and was blocked by the vesicular transporter inhibitor bafilomycin A1. In addition, 11-keto--boswellic acid reduced the 4-aminopyridine-induced increase in intrasynaptosomal Ca levels. The N- and P/Q-type channel blocker -conotoxin MVIIC and the protein kinase A inhibitor H89 significantly suppressed the 11-keto--boswellic acid-mediated inhibition of glutamate release, whereas the intracellular Ca-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--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--boswellic acid inhibits glutamate release from the rat hippocampal synaptosomes by suppressing N- and P/Q-type Ca channels and protein kinase A activity, as well as exerts protective effects against kainic acid-induced excitotoxicity .
过量的谷氨酸浓度会导致急性脑损伤和慢性神经退行性疾病中的神经元死亡。来自药用植物的天然化合物因其在预防和治疗神经紊乱方面的应用而受到广泛关注。11-酮-β-乳香酸是一种在药用植物中发现的三萜类化合物，具有神经保护潜力。本研究探讨了 11-酮-β-乳香酸对大鼠海马中谷氨酸释放和海人酸诱导的谷氨酸兴奋性毒性的影响。在大鼠海马神经末梢（突触体）中，11-酮-β-乳香酸剂量依赖性地抑制 4-氨基吡啶刺激的谷氨酸释放。这种作用依赖于细胞外钙，在谷氨酸转运体抑制剂 DL-threo-苯甲氧基天冬氨酸存在的情况下持续存在，并被囊泡转运体抑制剂巴弗洛霉素 A1 阻断。此外，11-酮-β-乳香酸降低了 4-氨基吡啶诱导的突触体内 Ca 水平升高。N 和 P/Q 型通道阻滞剂 -芋螺毒素 MVIIC 和蛋白激酶 A 抑制剂 H89 显著抑制 11-酮-β-乳香酸介导的谷氨酸释放抑制，而细胞内 Ca 释放抑制剂丹曲林、CGP37157 和 Xestospongin C、丝裂原激活蛋白激酶抑制剂 PD98059 以及蛋白激酶 C 抑制剂钙调蛋白 C 则没有作用。在腹腔注射海人酸（15mg/kg）诱导的兴奋性毒性大鼠模型中，腹腔注射 11-酮-β-乳香酸（10 或 50mg/kg）在海人酸注射前 30 分钟给药可显著改善海人酸诱导的谷氨酸浓度升高和 CA3 神经元死亡。这些数据表明，11-酮-β-乳香酸通过抑制 N 和 P/Q 型 Ca 通道和蛋白激酶 A 活性抑制大鼠海马突触体中的谷氨酸释放，并发挥对抗海人酸诱导的兴奋性毒性的保护作用。
