Department of Pharmaceutical Biology, Faculty of Pharmacy and Biotechnology, German University in Cairo, Main Entrance of Al Tagamoa Al Khames, New Cairo City, 11835, Egypt.
Biotechnology Sector, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt.
Mol Neurobiol. 2018 Jul;55(7):5798-5808. doi: 10.1007/s12035-017-0801-2. Epub 2017 Oct 27.
Neuroinflammation is one of the most important mechanisms underlying neurodegeneration. Lipopolysaccharide (LPS) is a potent inflammogen which causes cognitive dysfunction. Boswellia serrata is known since many years as a powerful anti-inflammatory herbal drug. Its beneficial effect mainly arises from inhibition of 5-lipoxygenase (5-LO) enzyme. 3-acetyl-11-keto-β-boswellic acid (AKBA) is the most potent 5-LO inhibitor extracted from the oleo-gum-resin of Boswellia serrata. The aim of the present work is to study the molecular mechanisms underlying the anti-inflammatory and neuroprotective effects of AKBA and dexamethasone (DEX) in LPS-induced neuroinflammatory model. A single intraperitoneal (i.p.) dose of LPS (0.8 mg/kg) was injected to induce cognitive dysfunction. The LPS-treated mice were administered for 7 days with either AKBA or DEX at intraperitoneal doses of 5 and 1 mg/kg, respectively. Cognitive, locomotor functions, and anxiety level were first examined. The level of the phosphorylated inhibitory protein for NF-κB, IκB-α (P-IκB-α), was measured, and the expression levels of the inflammatory microRNA-155 (miR-155) and its target gene, suppressor of cytokine signaling-1 (SOCS-1), were determined in the brain. Moreover, the level of carbonyl proteins as a measure of oxidative stress and several cytokines as well as markers for apoptosis and amyloidogenesis was detected. Results showed that AKBA and DEX reversed the behavioral dysfunction induced by LPS. AKBA decreased P-IκB-α, miRNA-155 expression level, and carbonyl protein content. It restored normal cytokine level and increased SOCS-1 expression level. It also showed anti-apoptotic and anti-amyloidogenic effects in LPS-injected mice. These findings suggest AKBA as a therapeutic drug for alleviating the symptoms of neuroinflammatory disorders.
神经炎症是神经退行性变的最重要机制之一。脂多糖（LPS）是一种有效的促炎物质，可导致认知功能障碍。乳香树是一种众所周知的具有强大抗炎作用的草药药物，多年来一直被用作抗炎药物。其有益作用主要源于对 5-脂氧合酶（5-LO）的抑制。3-乙酰基-11-酮-β-乳香酸（AKBA）是从乳香树的油胶树脂中提取的最有效的 5-LO 抑制剂。本研究的目的是研究 AKBA 和地塞米松（DEX）在 LPS 诱导的神经炎症模型中的抗炎和神经保护作用的分子机制。单次腹腔（i.p.）注射 LPS（0.8mg/kg）可诱导认知功能障碍。用 LPS 处理的小鼠连续 7 天腹腔内分别给予 AKBA 或 DEX（5 和 1mg/kg），然后检测认知、运动功能和焦虑水平。测量磷酸化核因子-κB 抑制蛋白 IκB-α（P-IκB-α）的水平，并测定脑内炎症 microRNA-155（miR-155）及其靶基因抑制细胞因子信号转导 1（SOCS-1）的表达水平。此外，还检测了羰基蛋白（作为氧化应激的衡量标准）以及几种细胞因子以及凋亡和淀粉样蛋白形成的标志物的水平。结果表明，AKBA 和 DEX 逆转了 LPS 诱导的行为功能障碍。AKBA 降低了 P-IκB-α、miR-155 的表达水平和羰基蛋白含量。它恢复了正常的细胞因子水平并增加了 SOCS-1 的表达水平。它还在 LPS 注射的小鼠中表现出抗凋亡和抗淀粉样蛋白形成的作用。这些发现表明 AKBA 可作为治疗神经炎症性疾病的药物。
