槟榔是继尼古丁之后世界上消费最广泛的成瘾物质之一,乙醇,和咖啡因。槟榔碱是槟榔的活性成分。它具有许多药理作用,可以影响中枢神经系统。在这项研究中,我们发现槟榔碱可以缓解疲劳行为。
目的:本研究旨在使用睡眠剥夺(SD)诱发的中枢疲劳的小鼠模型来评估槟榔碱的抗疲劳作用并探索其潜在机制。
方法:将72只雄性C57BL/6小鼠随机分为6组:对照组,SD疲劳模型组,一组接受红景天胶囊(2.5mg/kg),和三个槟榔碱小组,在低的时候给药,中等,和高剂量(10、20和40毫克/千克,分别)。连续给药28天后,通过行为测试评估槟榔碱对小鼠疲劳相关行为的影响,包括握力,转杆性能,和负重游泳耐力。通过酶联免疫吸附测定(ELISA)测量相关生化标志物的释放水平。Westernblotting用于定量核因子红细胞2相关因子(Nrf2)的表达水平,Kelch样ECH相关蛋白1(Keap1),血红素加氧酶1(HO-1),隔离体-1(p62),和NADPH醌氧化还原酶1(NQO1)在腓肠肌中。
结果:槟榔碱给药显著增强握力,延迟疲劳的发作,证明了延长潜伏期在转杆试验,并增加小鼠负重游泳的持续时间。在高架加迷宫中,槟榔林明显减少了入口的数量和张开双臂行进的总距离。槟榔碱显着降低肌酸激酶的含量,血尿素氮,乳酸脱氢酶,甘油三酯,血清中的胆固醇,虽然它提高了总睾酮的水平,乳酸脱氢酶,和免疫球蛋白G。此外,显著提高超氧化物歧化酶(SOD)活性,过氧化氢酶(CAT),和腓肠肌中的谷胱甘肽过氧化物酶,降低丙二醛水平,增强海马SOD和CAT活性,以及肝脏和肌肉组织中糖原储存的升高。神经递质水平显着增加,细胞因子水平明显降低,脑组织中Nrf2、Keap1、NQO1、p62和HO-1的表达明显上调。
结论:本研究表明槟榔碱具有抗疲劳活性,具体机制与葡萄糖和脂质代谢水平升高有关,缓解氧化应激损伤,抑制神经炎症反应,并调节神经递质水平和Keap1/Nrf2/HO-1信号通路。该研究为槟榔碱在预防和改善疲劳方面的潜力提供了新的方向。
The betel nut is one of the most widely consumed addictive substances in the world after nicotine, ethanol, and caffeine. Arecoline is an active ingredient from the areca nut. It has many pharmacological effects and can affect the central nervous system. In this study, we found that arecoline can relieve fatigue behavior.
OBJECTIVE: This research aims to estimate the anti-fatigue effects of arecoline and explore its underlying mechanisms using a murine model of central fatigue precipitated by sleep deprivation (SD).
METHODS: Seventy-two male C57BL/6 mice were randomly assigned to six groups: a control group, an SD-induced fatigue model group, a group that received Rhodiola Rosea capsules (2.5 mg/kg), and three arecoline groups, which were administered at low, medium, and high doses (10, 20, and 40 mg/kg, respectively). Following 28 days of continuous administrations, the effects of arecoline on mouse fatigue-related behaviors were assessed by behavioral tests, including grip strength, rotarod performance, and weight-bearing swimming endurance. The release levels of the related biochemical markers were measured by enzyme-linked immunosorbent assays (ELISAs). Western blotting was employed to quantify the expression levels of nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase 1 (HO-1), sequestosome-1 (p62), and NADPH quinone oxidoreductase 1 (NQO1) in the gastrocnemius muscle.
RESULTS: Arecoline administration notably enhanced grip strength, delayed the onset of fatigue as evidenced by extended latencies in rotarod tests, and increased the duration of weight-bearing swimming in mice. In the elevated plus maze, arecoline obviously decreased both the number of entries and the total distance traveled in the open arms. Arecoline markedly decreased the contents of creatine kinase, blood urea nitrogen, lactate dehydrogenase, triglycerides, and cholesterol in the serum, while it elevated the levels of total testosterone, lactate dehydrogenase, and immunoglobulin G. Furthermore, it significantly increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase in the gastrocnemius muscle, reduced malondialdehyde levels, augmented hippocampal SOD and CAT activity, and elevated glycogen stores in both liver and muscle tissues. Neurotransmitter levels showed significant increases, cytokine levels were markedly reduced, and the expressions of Nrf2, Keap1, NQO1, p62, and HO-1 in brain tissues were significantly upregulated.
CONCLUSIONS: This study demonstrates that arecoline has anti-fatigue activity, and the specific mechanisms are associated with elevating glucose and lipid metabolism levels, relieving oxidative stress damage, inhibiting neuroinflammatory response, and regulating neurotransmitter levels and the Keap1/Nrf2/HO-1 signaling pathway. The research provides a new direction for arecoline\'s potential in preventing and improving fatigue.