Ageing Biology Lab, Microbial Technology and Nematology Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
Process Chemistry & Chemical Engineering Department, CSIR-Central Institute of Medicinal and Aromatic Plants, Lucknow 226015, India.
Exp Gerontol. 2019 Jun;120:50-61. doi: 10.1016/j.exger.2019.02.016. Epub 2019 Feb 28.
Ageing is a progressive deterioration in functional and structural well-being of the body, accompanied with age-associated neurological disorders such as Parkinson's disease (PD), Alzheimer's disease and Huntington's disease. PD is marked with motor function decline, progressive neurodegeneration due to aggregation of insoluble α-synuclein in the dopaminergic neuron. Here we investigated the effect of tambulin (3,5-dihydroxy-7,8-dimethoxy-2-(4-methoxyphenyl) chromen-4-one), a hydroxy substituted flavanol isolated from fruits of Zanthoxyllum armatum DC (Family-Rutaceae) for its longevity promoting and neuromodulatory activities using Caenorhabditis elegans model system. Our results show that tambulin treatment significantly enhance lifespan and stress tolerance in worms, along with mitigation of ageing biomarkers like lipofuscin and protein carbonyl. In line with the alleviated ROS levels, tambulin treatment led to upregulated mRNA expression of ROS scavenging genes viz., sod-1, sod-3, and ctl-2. Upregulation in daf-16 gene indicates the involvement of insulin signaling pathway in tambulin mediated longevity. Tambulin treatment exhibited curtailed PD manifestations in terms of reduced α-synuclein levels, lipid accumulation, improved locomotary behavior and dopamine levels. Altogether, our data suggest that tambulin mediated alleviation of PD manifestations possibly involved PD counter protective machinery as evident through upregulated mRNA expression of lagr-1, ymel-1, pdr-1, ubc-12, and lrk-1. Our studies present tambulin as a potential molecule for its properties against ageing and Parkinson's disease. Further studies are speculated to realize the mechanistic and pharmacological aspects of tambulin.
衰老是身体功能和结构健康状况的逐渐恶化，伴随着与年龄相关的神经紊乱，如帕金森病（PD）、阿尔茨海默病和亨廷顿病。PD 的特点是运动功能下降，由于多巴胺神经元中不溶性α-突触核蛋白的聚集导致进行性神经退行性变。在这里，我们研究了 tambulin（3,5-二羟基-7,8-二甲氧基-2-(4-甲氧基苯基）色烯-4-酮），一种从 Zanthoxyllum armatum DC（芸香科）的果实中分离出的羟基取代黄烷醇，对其长寿促进和神经调节活性，使用秀丽隐杆线虫模型系统。我们的结果表明， tambulin 处理可显著延长线虫的寿命并提高其应激耐受性，同时减轻脂褐素和蛋白质羰基等衰老生物标志物的积累。与 ROS 水平降低一致， tambulin 处理导致 ROS 清除基因 sod-1、sod-3 和 ctl-2 的 mRNA 表达上调。daf-16 基因的上调表明胰岛素信号通路参与了 tambulin 介导的长寿。Tambulin 处理可减少α-突触核蛋白水平、脂质积累、改善运动行为和多巴胺水平，从而减轻 PD 表现。总的来说，我们的数据表明，Tambulin 通过上调 lagr-1、ymel-1、pdr-1、ubc-12 和 lrk-1 的 mRNA 表达，减轻 PD 表现可能涉及 PD 对抗保护机制。我们的研究表明，Tambulin 是一种潜在的分子，具有抗衰老和帕金森病的特性。进一步的研究预计将实现 Tambulin 的机制和药理学方面。
