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.

中文翻译：

---

11-酮-β-乳香酸减弱大鼠海马中谷氨酸释放和红藻氨酸诱导的兴奋性毒性

谷氨酸浓度过高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系统疾病方面的用途而引起了相当大的关注。11-Keto-β-boswellic acid 是一种在药用植物 Boswellia serrata 中发现的三萜类化合物，具有神经保护潜力。本研究调查了 11-酮-β-乳香酸对体外谷氨酸释放和海马酸诱导的大鼠海马体内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。这种效应依赖于细胞外钙，在谷氨酸转运蛋白抑制剂 DL-threo-β-苄氧基天冬氨酸存在下持续存在，并被囊泡转运蛋白抑制剂巴弗洛霉素 A1 阻断。此外，11-酮-β-乳香酸减少了 4-氨基吡啶诱导的突触内 Ca2+ 水平增加。N 型和 P/Q 型通道阻滞剂 ω-芋螺毒素 MVIIC 和蛋白激酶 A 抑制剂 H89 显着抑制了 11-酮-β-乳香酸介导的谷氨酸释放抑制，而细胞内 Ca2+ 释放抑制剂丹曲林 CGP37157和 xestospongin C、丝裂原活化蛋白激酶抑制剂 PD98059 以及蛋白激酶 C 抑制剂钙磷蛋白 C 没有影响。在腹腔注射红藻氨酸 (15 mg/kg) 诱导的兴奋性毒性大鼠模型中，在注射红藻氨酸前 30 分钟腹膜内注射 11-酮-β-乳香酸（10 或 50 mg/kg）可显着改善红藻氨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 Ca2+ 通道和蛋白激酶 A 活性来抑制大鼠海马突触体中谷氨酸的释放，并对红藻氨酸诱导的兴奋性毒性发挥保护作用体内。