Ju Zhang1, Ruona Shi2, Haifeng Li3, Yanxia Xiang4, Lingyun Xiao5, Minghua Hu6, Fangli Ma7, Chung Wah Ma8, Zebo Huang9. 1. 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. Electronic address: juzi437163804@163.com. 2. Center for Bioresources & Drug Discovery and School of Biosciences & Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: 15521217084@163.com. 3. Center for Bioresources & Drug Discovery and School of Biosciences & Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: lihf@gdpu.edu.cn. 4. School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China. Electronic address: yanxia@whu.edu.cn. 5. School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China; Research & Development Center, Infinitus (China) Company Ltd., Guangzhou 510665, China. Electronic address: Mandy.Xiao@infinitus-int.com. 6. Research & Development Center, Infinitus (China) Company Ltd., Guangzhou 510665, China. Electronic address: mandy.hu@infinitus-int.com. 7. Research & Development Center, Infinitus (China) Company Ltd., Guangzhou 510665, China. Electronic address: mary.ma@infinitus-int.com. 8. Research & Development Center, Infinitus (China) Company Ltd., Guangzhou 510665, China. Electronic address: william.ma@infinitus-int.com. 9. 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; Guangdong Province Key Laboratory for Biotechnology Drug Candidates, Guangdong Pharmaceutical University, Guangzhou 510006, China. Electronic address: zebohuang@gdpu.edu.cn.
Abstract
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-β 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.
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-β protein. CONCLUSIONS: These findings demonstrate the antioxidant and neuroprotective activities of the D. indusiatapolysaccharideDiPS in wild-type and neurodegenerative C. elegans models, and thus provide an important pharmacological basis for the therapeutic potential of D. indusiata in neurodegeneration.
Authors: Benjamin Dilberger; Stefan Baumanns; Fabian Schmitt; Tommy Schmiedl; Martin Hardt; Uwe Wenzel; Gunter P Eckert Journal: Oxid Med Cell Longev Date: 2019-11-15 Impact factor: 6.543