Abstract：
The study objectives are to investigate the ability of capsaicin to revert the toxic effects in glutamate and lipopolysaccharide (LPS)-induced neurotoxicity in Neuro2a (N2a) cells as well as thwarting cognitive impairments, mitochondrial deficits, and oxidative insults induced by 3-nitropropanoic acid (3-NP) in a rodent model of Huntington\'s disease. In-vitro study with N2a cells was performed through MTT and LDH assay and their biochemical examinations were also performed. 3-NP-administered mice (n = 6) were treated with capsaicin (5, 10, and 20 mg/kg) through the per-oral (p.o.) route for 7 consecutive days. Physiological and behavioral studies were performed in drug-treated mice. After behavioral studies, biochemical parameters were performed for cytokines levels, various oxidative stress parameters, and mitochondrial enzyme complex activities with mitochondrial permeability. N2a cells treated with capsaicin demonstrated neuroprotective effects and reduced neurotoxicity. Based on experimental observation, in an in-vitro study, the effective dose of CAP was 50 µM. Moreover, a 100 µM dose of capsaicin had toxic effects on neuronal cells (N2a cells). On the other hand, the effective dose of 3-NP was 20 mg/kg, (p.o.) in animals (in-vivo). All tested doses of capsaicin upturned the cognitive impairment and motor in-coordination effects induced by 3-NP. 3-NP-injected mice demonstrated substantially increased pro-inflammatory cytokine concentrations, defective mitochondrial complex activity, and augmented oxidative insult. However, capsaicin at different doses reduced oxidative damage and cytokines levels and improved mitochondrial complex activity along with mitochondrial permeability. Furthermore, capsaicin (10 and 20 mg/kg) improved the TNF-α concentration. These findings suggested because of the anti-inflammatory and antioxidant effect, capsaicin can be considered a novel treatment for the management of neurodegenerative disorders by reverting the antioxidant enzyme activity, pro-inflammatory cytokines concentration, and mitochondrial functions.
摘要：
研究目的是研究辣椒素恢复谷氨酸和脂多糖（LPS）诱导的Neuro2a（N2a）细胞神经毒性的毒性作用以及阻止认知障碍的能力。线粒体缺陷,和3-硝基丙酸（3-NP）在亨廷顿氏病啮齿动物模型中诱导的氧化损伤。通过MTT和LDH测定进行了N2a细胞的体外研究，并进行了生化检查。通过口服(p.o.)途径用辣椒素(5、10和20mg/kg)连续7天处理施用3-NP的小鼠(n=6)。在药物处理的小鼠中进行生理和行为研究。在行为研究之后,生化参数进行细胞因子水平，各种氧化应激参数，和线粒体酶复合物活性与线粒体通透性有关。用辣椒素处理的N2a细胞表现出神经保护作用和降低的神经毒性。根据实验观察,在一项体外研究中，CAP的有效剂量为50µM。此外，100µM剂量的辣椒素对神经元细胞（N2a细胞）有毒性作用。另一方面,3-NP的有效剂量为20mg/kg，（p.o.）在动物中（体内）。所有测试剂量的辣椒素都可以改善3-NP引起的认知障碍和运动协调作用。注射3-NP的小鼠表现出显著增加的促炎细胞因子浓度，线粒体复合物活性缺陷，和增强的氧化侮辱。然而,不同剂量的辣椒素降低了氧化损伤和细胞因子水平，并改善了线粒体复合物的活性以及线粒体的通透性。此外，辣椒素(10和20mg/kg)提高了TNF-α浓度。这些发现表明，由于抗炎和抗氧化作用，辣椒素可以被认为是一种通过恢复抗氧化酶活性来管理神经退行性疾病的新治疗方法，促炎细胞因子浓度，和线粒体功能。
