ABSTRACT
Epimedium has been traditionally used to treat a variety of medical conditions, including neurological disorders. In this study, an acidic polysaccharide EbPS-A1 is isolated from Epimedium brevicornum and found to contain mainly galacturonic acid, galactose, and rhamnose but also arabinose and glucuronic acid. Using Caenorhabditis elegans models, we show that EbPS-A1 is capable of inhibiting behavioral dysfunction mediated by polyglutamine (polyQ), which is implicated in several neurodegenerative disorders such as Huntington's disease. Interestingly, EbPS-A1 does not inhibit polyQ aggregation or extend lifespan in the nematodes; it does, however, improve the survival under increased oxidative stress of both polyQ and wild-type nematodes intoxicated by paraquat. Further studies reveal that EbPS-A1 is capable of not only scavenging free radicals in vitro but also reducing reactive oxygen species levels, enhancing antioxidant enzyme activities, and decreasing lipid peroxidation product in C. elegans models. Together, these results suggest that the protective effect of Epimedium polysaccharide against polyQ-mediated neurotoxicity is likely due to its antioxidant function.
Subject(s)
Caenorhabditis elegans/drug effects , Epimedium/chemistry , Neurotoxins/toxicity , Oxidative Stress/drug effects , Peptides/toxicity , Polysaccharides/pharmacology , Animals , Antioxidants/metabolism , Behavior, Animal/drug effects , Chemical Fractionation , Free Radical Scavengers/pharmacology , Malondialdehyde/metabolism , Protein Aggregates/drug effects , Survival AnalysisABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: 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. MATERIALS AND METHODS: 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. RESULTS: 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-ß protein. CONCLUSIONS: 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.
Subject(s)
Agaricales/chemistry , Antioxidants/pharmacology , Caenorhabditis elegans/drug effects , Nerve Degeneration , Neurons/drug effects , Neuroprotective Agents/pharmacology , Neurotoxicity Syndromes/prevention & control , Oxidative Stress/drug effects , Polysaccharides/pharmacology , Adenosine Triphosphate/metabolism , Amyloid beta-Peptides/toxicity , Animals , Animals, Genetically Modified , Antioxidants/isolation & purification , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Dose-Response Relationship, Drug , Energy Metabolism/drug effects , Malondialdehyde/metabolism , Membrane Potential, Mitochondrial/drug effects , Mitochondria/drug effects , Mitochondria/metabolism , Mitochondria/pathology , Neurons/metabolism , Neurons/pathology , Neuroprotective Agents/isolation & purification , Neurotoxicity Syndromes/genetics , Neurotoxicity Syndromes/metabolism , Neurotoxicity Syndromes/pathology , Paraquat/toxicity , Peptides/toxicity , Polysaccharides/isolation & purification , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolism , Time FactorsABSTRACT
Tsai Tai is one of the most widely consumed Brassica vegetables in Asian countries because of its good taste and its nutritional benefits. This study evaluated the antioxidant capacity and possible associated health benefits of 3 Tsai Tai (Brassica chinensis) varieties, namely, Hon Tsai Tai, Pak Choi and Choi Sum. The DPPH radical scavenging ability and reducing power assays were performed to evaluate the in vitro activities of the extracts. Caenorhabditis elegans was used as an in vivo model for evaluation of beneficial health effects, including antioxidant activity and delayed aging. In vitro, the Hon Tsai Tai extract exhibited higher antioxidant activities than Pak Choi and Choi Sum, and the total phenolic contents were significantly correlated with the DPPH and RP values. In vivo, the three assayed Tsai Tai extracts significantly increased resistance against paraquat-induced oxidative stress with an increase in survival rates from 15% to 28% compared with controls. However, only the extract from Hon Tsai Tai significantly prolonged the lifespan of Caenorhabditis elegans, with an 8% increase in the mean lifespan with respect to controls. Further evidence of antioxidant protection was obtained by assessing ROS production via the DCF assay. The analyses of intracellular SOD activity and MDA content confirmed the existence of an antioxidant protective effect. These results suggest that Tsai Tai might serve as a good source of natural antioxidants, and in particular, Hon Tsai Tai could be explored as a potential dietary supplement to retard aging.
Subject(s)
Aging/drug effects , Antioxidants/pharmacology , Brassica/chemistry , Caenorhabditis elegans/drug effects , Plant Extracts/pharmacology , Animals , Anthocyanins/analysis , Anthocyanins/pharmacology , Antioxidants/analysis , Caenorhabditis elegans/physiology , Malondialdehyde/metabolism , Oxidative Stress/drug effects , Phenols/analysis , Phenols/pharmacology , Plant Extracts/analysis , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolismABSTRACT
Recent studies have uncovered important aging clues, including free radicals, inflammation, telomeres, and life span pathways. Strategies to regulate aging-associated signaling pathways are expected to be effective in the delay and prevention of age-related disorders. For example, herbal polysaccharides with considerable anti-oxidant and anti-inflammation capacities have been shown to be beneficial in aging and age-related neurodegenerative diseases. Polysaccharides capable of reducing cellular senescence and modulating life span via telomere and insulin pathways have also been found to have the potential to inhibit protein aggregation and aggregation-associated neurodegeneration. Here we present the current status of polysaccharides in anti-aging and anti-neurodegenerative studies.
