Rai Sachchida Nand, Birla Hareram, Zahra Walia, Singh Saumitra Sen, Singh Surya Pratap
Department of Biochemistry, Institute of Science, Banaras Hindu University, Varanasi, 221005, India.
J Chem Neuroanat. 2017 Nov;85:27-35. doi: 10.1016/j.jchemneu.2017.06.005. Epub 2017 Jun 19.
Immune control is associated with nigrostriatal neuroprotection for Parkinson's disease (PD); though its direct cause and effect relationships have not yet been realized and modulating the immune system for therapeutic gain has been openly discussed. While the pathobiology of PD remains in study, neuroinflammation is thought to speed nigrostriatal degeneration. The neuroinflammatory cascade associated with PD begins with aggregation of misfolded or post-translationally modified α-synuclein (α-syn). Such aggregation results in neuronal cell death and the presence of chronically activated glia (microglia and astroglia), leading to the production of proinflammatory cytokines like tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, and enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and cyclooxygenase-2 (COX-2). These changes in the glial phenotype can affect the central nervous system (CNS) microenvironment by producing a pro-inflammatory milieu that speeds PD pathogenesis. Mucuna pruriens (Mp) is the most popular drug in Ayurveda, the Indian system of medicine. Several reports have suggested that it possesses analgesic, anti-inflammatory, anti-neoplastic, anti-epileptic and anti-microbial activities. Mp contain L-DOPA and ursolic acid which has an anti-inflammatory property. There are very few literatures which show the immunomodulatory activity of Mp in PD, several researchers have tried to work on the immunomodulatory activity of Mp in some other diseases. The results of several studies show that Mp modulate the immune components like TNF-α, IL-6, IFN-λ, IL-1β, iNOS and IL-2 in the CNS. It also modulates the activity of the transcription factor NF-kB which plays an important role in the progression of the PD. Thus, by altering these cytokines or transcription factors, Mp protects or prevents the progression of PD. Thus in this review we try to explore the immunomodulatory activity of Mp in PD.
免疫控制与帕金森病(PD)的黑质纹状体神经保护相关;尽管其直接的因果关系尚未明确,且通过调节免疫系统实现治疗获益已被公开讨论。虽然PD的病理生物学仍在研究中,但神经炎症被认为会加速黑质纹状体变性。与PD相关的神经炎症级联反应始于错误折叠或翻译后修饰的α-突触核蛋白(α-syn)的聚集。这种聚集导致神经元细胞死亡以及慢性活化的胶质细胞(小胶质细胞和星形胶质细胞)的存在,进而导致促炎细胞因子如肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6的产生,以及烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶和环氧化酶-2(COX-2)等酶的产生。胶质细胞表型的这些变化可通过产生促炎微环境来影响中枢神经系统(CNS)微环境,从而加速PD的发病机制。刺蒺藜(Mp)是印度阿育吠陀医学体系中最常用的药物。多项报告表明它具有镇痛、抗炎、抗肿瘤、抗癫痫和抗菌活性。Mp含有左旋多巴和具有抗炎特性的熊果酸。很少有文献显示Mp在PD中的免疫调节活性,一些研究人员曾尝试研究Mp在其他一些疾病中的免疫调节活性。多项研究结果表明,Mp可调节中枢神经系统中的免疫成分,如TNF-α、IL-6、IFN-λ、IL-1β、诱导型一氧化氮合酶(iNOS)和IL-2。它还可调节转录因子NF-κB的活性,而NF-κB在PD的进展中起重要作用。因此,通过改变这些细胞因子或转录因子,Mp可保护或防止PD的进展。因此,在本综述中,我们试图探讨Mp在PD中的免疫调节活性。