Department of Pathophysiology, Key Laboratory of the State Administration of Traditional Chinese Medicine, Medical College of Jinan University, Guangzhou, Guangdong Province, China.
Department of Orthopedics, The First Affiliated Hospital, Medical College of Jinan University, Guangzhou, Guangdong Province, China.
Neurosci Lett. 2019 Sep 14;709:134386. doi: 10.1016/j.neulet.2019.134386. Epub 2019 Jul 19.
Neuroinflammation is a predisposing factor for several neurodegenerative diseases. The purpose of this study was to evaluate the protective effect of madecassoside (MA) in lipopolysaccharide (LPS)-induced cognitive impairment and neuroinflammation in rats. MA has many protective effects such as antioxidant and anti-inflammatory properties. We investigated whether MA could improve neurocognitive dysfunction caused by intracerebroventricular injection of LPS. We examined the effects and mechanisms of action of MA on LPS-induced neuroinflammation in the cortex and hippocampus. Our study revealed that MA (120 mg/kg, i.g) treatment for 14 days reduced LPS-induced neurotoxicity by reducing cognitive impairments and suppressing the production of inflammatory cytokines such as interleukin 1 beta (IL-1β), tumor necrosis factor alpha(TNF-α), and interleukin 6(IL-6) via activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. Furthermore, MA treatment enhanced protein levels of heme oxygenase (HO)-1 by upregulating Nrf2 in LPS-stimulated neurotoxicity. Collectively, these results suggest that MA is effective in preventing neurodegenerative diseases by improving memory functions due to its anti-inflammatory activities and activation of Keap1-Nrf2/HO-1 signaling. As such, MA may be a potential therapy for addressing memory impairment caused by neuroinflammation.
神经炎症是几种神经退行性疾病的诱发因素。本研究旨在评估马卡因（MA）对脂多糖（LPS）诱导的大鼠认知障碍和神经炎症的保护作用。MA 具有许多保护作用，如抗氧化和抗炎特性。我们研究了 MA 是否可以改善 LPS 脑室内注射引起的神经认知功能障碍。我们研究了 MA 对皮质和海马中 LPS 诱导的神经炎症的作用和作用机制。我们的研究表明，MA（120mg/kg，ig）治疗 14 天可通过减少认知障碍和抑制白细胞介素 1β（IL-1β）、肿瘤坏死因子α（TNF-α）和白细胞介素 6（IL-6）等炎症细胞因子的产生，减轻 LPS 诱导的神经毒性，从而激活核因子红细胞 2 相关因子 2（Nrf2）信号通路。此外，MA 处理通过上调 LPS 刺激的神经毒性中的 Nrf2，增强血红素加氧酶（HO）-1 的蛋白水平。总之，这些结果表明，MA 通过抗炎活性和激活 Keap1-Nrf2/HO-1 信号通路改善记忆功能，从而有效预防神经退行性疾病。因此，MA 可能是治疗神经炎症引起的记忆障碍的一种潜在疗法。
