Anti-ageing and anti-Parkinsonian effects of natural flavonol, tambulin from Zanthoxyllum aramatum promotes longevity in Caenorhabditis elegans

被引:37
作者
Pandey, Taruna [1 ]
Sammi, Shreesh Raj [1 ]
Nooreen, Zulfa [2 ]
Mishra, Anjali [3 ]
Ahmad, Ateeque [2 ]
Bhatta, Rabi S. [3 ]
Pandey, Rakesh [1 ]
机构
[1] Cent Inst Med & Aromat Plants, CSIR, Microbial Technol & Nematol Dept, Ageing Biol Lab, Lucknow 226015, Uttar Pradesh, India
[2] Cent Inst Med & Aromat Plants, CSIR, Proc Chem & Chem Engn Dept, Lucknow 226015, Uttar Pradesh, India
[3] Cent Drug Res Inst, CSIR, Pharmacokinet & Metab Div, Lucknow 226031, Uttar Pradesh, India
关键词
Tambulin; Reactive oxygen species; Ageing; Parkinson's disease; alpha-Synuclein; Caenorhabditis elegans; LIFE-SPAN EXTENSION; ALPHA-SYNUCLEIN; C; ELEGANS; DOPAMINERGIC-NEURONS; STRESS RESISTANCE; OXIDATIVE STRESS; DISEASE; ARMATUM; GENES; NEURODEGENERATION;
D O I
10.1016/j.exger.2019.02.016
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
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 alpha-synuclein in the dopaminergic neuron. Here we investigated the effect of tambulin (3,5-dihydroxy-7,8-di-methoxy-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 alpha-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.
引用
收藏
页码:50 / 61
页数:12
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