机构:[1]College of Life Sciences, Lanzhou University, Lanzhou 730000, China.[2]School of Pharmacy, Lanzhou University, Donggang West Road No. 199, Lanzhou 730020, P. R. China.[3]Department of Neurology, Xuanwu Hospital of Capital Medical University, Beijing 100053, China.神经科系统神经内科首都医科大学宣武医院[4]Clinical Center for Parkinson's Disease, Capital Medical University, Beijing 100053, China.[5]Instiute of Biology Gansu Academy of Sciences, Lanzhou, Gansu 730000, China.
Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the central nervous system in the elderly, causing motor impediments and cognitive dysfunctions. Dopaminergic (DA) neuron degeneration and α-synuclein (α-Syn) accumulation in substantia nigra pars compacta are the major contributors to this disease. At present, PD remains untreatable with a huge burden on the quality of life. Therefore, we attempt to explore novel treatment strategies by detecting effective drugs that stop or arrest PD's progression via modifying disease-specific pathways. Chrysin is a flavonoid derived from passion flowers and possesses anti-cancer, anti-inflammatory, anti-oxidant, and anti-depression properties. In the present study, we assessed the neuroprotective potential of chrysin in transgenic Caenorhabditis elegans models of PD. We observed that chrysin reduced the aggregative toxicity of α-Syn and diminished DA neuron degeneration induced by 6-hydroxydopamine (6-OHDA), reduced food-sensing behavioral disabilities, and expanded the nematodes' lifespan. Moreover, chrysin augmented the ubiquitin-like proteasome and superoxide dismutase activities in transgenic C. elegans models. Further, we observed the anti-oxidative role of chrysin by reducing the internal cellular reactive oxygen species levels in 6-OHDA-intoxicated C. elegans. Together, these findings supported chrysin as a possible treatment for PD and encouraged further investigation of chrysin's mechanism of action as a neuroprotective medicine in the future.
基金:
We sincerely thank all the participants of this study; in
particular, Dr. Liu Yan is gratefully acknowledged for her
assistance in writing and guidance in experimental work.
Nematode strains used in this work were provided by the
Caenorhabditis Genetics Center (CGC), University of
Minnesota, MN, USA. This experimental study was funded
by the Natural Science Foundation of Gansu Province of
China (20JR10RA596 and 20JR10RA756) and the Talent
Innovation and Entrepreneurship Project of Lanzhou City
(2020-RC-43).
第一作者机构:[1]College of Life Sciences, Lanzhou University, Lanzhou 730000, China.
共同第一作者:
通讯作者:
通讯机构:[1]College of Life Sciences, Lanzhou University, Lanzhou 730000, China.[2]School of Pharmacy, Lanzhou University, Donggang West Road No. 199, Lanzhou 730020, P. R. China.[*1]College of Life Sciences, Lanzhou University, Lanzhou 730000, China[*2]School of Pharmacy, Lanzhou University, Lanzhou 730020, P. R. China
推荐引用方式(GB/T 7714):
Muhammad Fahim,Liu Yan,Wang Ningbo,et al.Anti-α-synuclein Toxicity and Anti-neurodegenerative Role of Chrysin in Transgenic Caenorhabditis elegans Models of Parkinson's Disease.[J].ACS CHEMICAL NEUROSCIENCE.2022,13(4):442-453.doi:10.1021/acschemneuro.1c00548.
APA:
Muhammad Fahim,Liu Yan,Wang Ningbo,Zhao Longhe,Zhou Yongtao...&Li Hongyu.(2022).Anti-α-synuclein Toxicity and Anti-neurodegenerative Role of Chrysin in Transgenic Caenorhabditis elegans Models of Parkinson's Disease..ACS CHEMICAL NEUROSCIENCE,13,(4)
MLA:
Muhammad Fahim,et al."Anti-α-synuclein Toxicity and Anti-neurodegenerative Role of Chrysin in Transgenic Caenorhabditis elegans Models of Parkinson's Disease.".ACS CHEMICAL NEUROSCIENCE 13..4(2022):442-453