a Laboratory of Aging Biology, Department of Microbial Technology and Nematology , Central Institute of Medicinal and Aromatic Plants, Council of Scientific and Industrial Research , Lucknow , India.
b Pharmacokinetics and Metabolism Division , Central Drug Research Institute, Council of Scientific and Industrial Research , Lucknow , India.
Free Radic Res. 2017 Dec;51(11-12):954-969. doi: 10.1080/10715762.2017.1395419. Epub 2017 Nov 16.
Shatavarin IV (SIV), a steroidal saponin, is a major bioactive phytomolecule present in roots of Asparagus racemosus (Liliaceae) known for its anticancer activity. Age-associated neurodegenerative Parkinson's disease (PD) is characterised by alpha-synuclein aggregation in dopaminergic neuron resulting in neurodegeneration. The invention of bioactive molecules that delay aging and age-associated disorders endorses development of natural phytomolecule as a therapeutic agent for curing age-related diseases. Therefore, the present study for the first time explores the potential of SIV against aging and Parkinsonism utilising Caenorhabditis elegans model system. SIV significantly attenuated oxidative stress in terms of intracellular reactive oxygen species (ROS) as well as oxidative damage including protein carbonylation and also promotes longevity. SIV also significantly increased the mRNA expression of stress responsive genes namely sod-1, sod-2, sod-3, gst-4, gst-7 and ctl-2 suggesting its anti-oxidant property that might be contributed in the modulation of oxidative stress and promoting lifespan. Additionally, SIV improved PD symptoms by reducing the alpha-synuclein aggregation, lipid accumulation and enhancing dopamine level. Altogether, present findings indicate that SIV possibly utilising ubiquitin-mediated proteasomal system and attenuating oxidative stress by up-regulating PD-associated genes pdr-1, ubc-12 and pink-1. Therefore, this study is a forward step in exploring the anti-aging and anti-Parkinsonism potential of bioactive compound SIV in C. elegans.
沙塔瓦林 IV（SIV）是一种甾体皂苷，是天门冬科植物天门冬（Liliaceae）根中的主要生物活性植物分子，具有抗癌活性。与年龄相关的神经退行性帕金森病（PD）的特征是α-突触核蛋白在多巴胺能神经元中的聚集，导致神经退行性变。具有延缓衰老和与年龄相关疾病的生物活性分子的发明，支持将天然植物分子作为治疗与年龄相关疾病的治疗剂的发展。因此，本研究首次利用秀丽隐杆线虫模型系统探索 SIV 对抗衰老和帕金森病的潜力。SIV 可显著减轻氧化应激，表现在细胞内活性氧（ROS）以及氧化损伤（包括蛋白质羰基化），并延长寿命。SIV 还显著增加了应激响应基因 sod-1、sod-2、sod-3、gst-4、gst-7 和 ctl-2 的 mRNA 表达，表明其具有抗氧化特性，这可能有助于调节氧化应激并延长寿命。此外，SIV 通过减少α-突触核蛋白聚集、脂质积累和提高多巴胺水平来改善 PD 症状。总之，目前的研究结果表明，SIV 可能通过利用泛素介导的蛋白酶体系统和上调与 PD 相关的基因 pdr-1、ubc-12 和 pink-1 来减轻氧化应激，从而发挥其抗衰老和抗帕金森病的作用。因此，这项研究是在秀丽隐杆线虫中探索生物活性化合物 SIV 的抗衰老和抗帕金森病潜力的一个重要进展。
