Zhang Ju, Shi Ruona, Li Haifeng, Xiang Yanxia, Xiao Lingyun, Hu Minghua, Ma Fangli, Ma Chung Wah, Huang Zebo
School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Center for Bioresources & Drug Discovery and School of Biosciences & Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Center for Bioresources & Drug Discovery and School of Biosciences & Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.
J Ethnopharmacol. 2016 Nov 4;192:413-422. doi: 10.1016/j.jep.2016.09.031. Epub 2016 Sep 17.
Dictyophora indusiata is a medicinal mushroom traditionally used in China for a variety of conditions, including inflammatory and neural diseases. D. indusiata polysaccharides (DiPS) are shown to have in vitro antioxidant activity but in vivo evidence is lacking. This study aimes to explore the antioxidant capacity and related neuroptotective activities of DiPS using wild-type and neurodegenerative Caenorhabditis elegans models.
The antioxidant capacities of DiPS were first determined using paraquat survival and Pgst-4::GFP expression assays in wild-type and transgenic C. elegans models, respectively, and then further investigated by determining reactive oxygen species (ROS) level, malondialdehyde (MDA) content and superoxide dismutase (SOD) activity as well as functional parameters of mitochondria. The activation of stress response transcription factors and neuroptotective activities were examined using nuclear localization and chemosensory behavioral assays in transgenic nematodes, respectively.
DiPS was shown not only to increase survival rate and reduce stress level under paraquat-induced oxidative conditions but also to decrease ROS and MDA levels and increase SOD activity in C. elegans models. Moreover, DiPS was also able to restore the functional parameters of mitochondria, including membrane potential and ATP content, in paraquat-stressed nematodes. In addition, nuclear translocation assays demonstrate that the stress response transcription factor DAF-16/FOXO was involved in the antioxidant activity of the polysaccharide. Further experiments reveal that DiPS was capable of reducing ROS levels and alleviating chemosensory behavior dysfunction in transgenic nematode models of neurodegenerative diseases mediated by polyglutamine and amyloid-β protein.
These findings demonstrate the antioxidant and neuroprotective activities of the D. indusiata polysaccharide DiPS in wild-type and neurodegenerative C. elegans models, and thus provide an important pharmacological basis for the therapeutic potential of D. indusiata in neurodegeneration.
竹荪是一种药用真菌,在中国传统上用于治疗多种病症,包括炎症性疾病和神经疾病。已证明竹荪多糖(DiPS)具有体外抗氧化活性,但缺乏体内证据。本研究旨在使用野生型和神经退行性秀丽隐杆线虫模型探索DiPS的抗氧化能力和相关神经保护活性。
首先分别在野生型和转基因秀丽隐杆线虫模型中使用百草枯存活试验和Pgst-4::GFP表达试验测定DiPS的抗氧化能力,然后通过测定活性氧(ROS)水平、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性以及线粒体功能参数进一步研究。分别在转基因线虫中使用核定位试验和化学感应行为试验检测应激反应转录因子的激活和神经保护活性。
结果表明,DiPS不仅能提高百草枯诱导的氧化条件下的存活率并降低应激水平,还能降低秀丽隐杆线虫模型中的ROS和MDA水平并提高SOD活性。此外,DiPS还能够恢复百草枯应激线虫中线粒体的功能参数,包括膜电位和ATP含量。此外,核转位试验表明应激反应转录因子DAF-16/FOXO参与了多糖的抗氧化活性。进一步的实验表明,DiPS能够降低转基因神经退行性疾病线虫模型中的ROS水平并减轻化学感应行为功能障碍,这些模型由多聚谷氨酰胺和淀粉样β蛋白介导。
这些发现证明了竹荪多糖DiPS在野生型和神经退行性秀丽隐杆线虫模型中的抗氧化和神经保护活性,从而为竹荪在神经退行性疾病中的治疗潜力提供了重要的药理学依据。