背景:人参是一种有价值的中药。现代研究表明,它有各种好处,包括补充生命能量,滋养和强身健体,平静的头脑,改善认知功能,调节流体,并恢复血压,等。Rg1是人参的主要活性成分。它保护海马神经元,改善突触可塑性,增强认知功能,增强免疫力.此外,它具有抗衰老和抗疲劳特性,并具有预防和管理神经退行性疾病(NDD)的巨大潜力。
目的:本研究的目的是研究Rg1治疗慢性炎症性NDDs的作用及其分子机制。
方法:体内,我们研究了Rg1对200μg/kg脂多糖(LPS)诱导21天的小鼠慢性神经炎症和认知缺陷的保护作用,病理切片,蛋白质印迹,qPCR和免疫染色。体外实验涉及用10μg/ml的LPS刺激HT22细胞,验证Rg1的治疗效果,并使用H2DCFDA染色阐明其潜在的作用机制,BODIPY™581/591C11,JC-1染色,蛋白质印迹,和免疫染色。
结果:首先,结果发现Rg1显著改善了LPS诱导的小鼠慢性行为和认知功能障碍。进一步研究表明,Rg1通过降低IL-6、IL-1β和ROS的水平,显著减轻LPS诱导的神经元损伤,并抑制AIM2炎性体。此外,慢性LPS暴露通过增加脂质过氧化产物MDA和调节铁凋亡相关蛋白Gpx4,xCT,FSP1、DMT1和TfR,被Rg1治疗逆转。此外,发现Rg1激活Nrf2及其下游抗氧化酶,如HO1和NQO1,在体内和体外。体外研究还表明,Nrf2抑制剂ML385可以抑制抗炎,抗氧化剂,和Rg1的抗铁凋亡作用。
结论:本研究表明,Rg1通过抑制神经炎症和氧化应激,改善了LPS诱导的小鼠慢性认知缺陷和神经元铁蛋白死亡。潜在的机制可能与AIM2炎性体的抑制和Nrf2信号的激活有关。这些发现为慢性神经炎症和相关NDD的治疗提供了有价值的见解。
BACKGROUND: Ginseng is a valuable herb in traditional Chinese medicine. Modern research has shown that it has various benefits, including tonifying vital energy, nourishing and strengthening the body, calming the mind, improving cognitive function, regulating fluids, and returning blood pressure, etc. Rg1 is a primary active component of ginseng. It protects hippocampal neurons, improves synaptic plasticity, enhances cognitive function, and boosts immunity. Furthermore, it exhibits anti-aging and anti-fatigue properties and holds great potential for preventing and managing neurodegenerative diseases (NDDs).
OBJECTIVE: The objective of this study was to examine the role of Rg1 in treating chronic inflammatory NDDs and its molecular mechanisms.
METHODS: In vivo, we investigated the protective effects of Rg1 against chronic neuroinflammation and cognitive deficits in mice induced by 200 μg/kg lipopolysaccharide (LPS) for 21 days using behavioral tests, pathological sections, Western blot, qPCR and immunostaining. In vitro experiments involved the stimulation of HT22 cells with 10 μg/ml of LPS, verification of the therapeutic effect of Rg1, and elucidation of its potential mechanism of action using H2DCFDA staining, BODIPY™ 581/591 C11, JC-1 staining, Western blot, and immunostaining.
RESULTS: Firstly, it was found that Rg1 significantly improved chronic LPS-induced behavioral and cognitive dysfunction in mice. Further studies showed that Rg1 significantly attenuated LPS-induced neuronal damage by reducing levels of IL-6, IL-1β and ROS, and inhibiting AIM2 inflammasome. Furthermore, chronic LPS exposure induced the onset of neuronal ferroptosis by increasing the lipid peroxidation product MDA and regulating the ferroptosis-associated proteins Gpx4, xCT, FSP1, DMT1 and TfR, which were reversed by Rg1 treatment. Additionally, Rg1 was found to activate Nrf2 and its downstream antioxidant enzymes, such as HO1 and NQO1, both in vivo and in vitro. In vitro studies also showed that the Nrf2 inhibitor ML385 could inhibit the anti-inflammatory, antioxidant, and anti-ferroptosis effects of Rg1.
CONCLUSIONS: This study demonstrated that Rg1 administration ameliorated chronic LPS-induced cognitive deficits and neuronal ferroptosis in mice by inhibiting neuroinflammation and oxidative stress. The underlying mechanisms may be related to the inhibition of AIM2 inflammasome and activation of Nrf2 signaling. These findings provide valuable insights into the treatment of chronic neuroinflammation and associated NDDs.