Aqueous extract of Gardenia jasminoides targeting oxidative stress to reduce polyQ aggregation in cell models of spinocerebellar ataxia 3.
Spinocerebellar ataxias (SCAs), caused by expanded CAG repeats encoding a long polyglutamine (polyQ) tract in the respective proteins, are characterized by the accumulation of intranuclear and cytoplasmic misfolded polyQ aggregation that leads to cell death. Suppression of aggregate formation can inhibit a wide range of downstream pathogenic events and is expected to be a therapeutic strategy for SCAs. Here we show the anti-aggregation potential of Gardenia jasminoides (G. jasminoides) and its components/metabolite geniposide, crocin, and genipin, in ATXN3/Q75-GFP 293 cells, a putative SCA3 cell model. We found the aggregation can be significantly prohibited by G. jasminoides, genipin, geniposide and crocin. Meanwhile, G. jasminoides, genipin, geniposide, and crocin up-regulated anti-oxidative markers NFE2L2, NQO1, GCLC and GSTP1, and reduced the production of reactive oxidative species (ROS) in the same cell models. All of them further inhibited the aggregation in neurally differentiated SH-SY5Y ATXN3/Q75-GFP cells. Our results demonstrate that G. jasminoides, genipin, geniposide and crocin work on polyQ-aggregation reduction by suppressing ROS. These findings indicate the therapeutic applications of G. jasminoides in treating SCAs. Furthermore, oxidative stress inhibition could be a good target for drug development of anti-polyQ aggregation.
Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei 10507, Taiwan.
Kuo-Hsuan
KH
Chang
Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei 10507, Taiwan.
Wan-Ling
WL
Chen
Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei 10507, Taiwan.
Yih-Ru
YR
Wu
Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan.
Te-Hsien
TH
Lin
Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan.
Yi-Ci
YC
Wu
Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei 10507, Taiwan.
Chih-Ying
CY
Chao
Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan; Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei 11051, Taiwan.
Jung-Yaw
JY
Lin
Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan.
Li-Ching
LC
Lee
Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei 10507, Taiwan.
Yi-Chun
YC
Chen
Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan. Electronic address: t43019@ntnu.edu.tw.
Guey-Jen
GJ
Lee-Chen
Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei 10507, Taiwan. Electronic address: cmchen@adm.cgmh.org.tw.
Chiung-Mei
CM
Chen
D000975:Antioxidants / Q000494:pharmacology*; D000067699:Ataxin-3; D001713:Biphenyl Compounds / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D039821:Monoterpenes / Q000737:chemistry / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D010851:Picrates / Q000378:metabolism; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D000975:Antioxidants; D001713:Biphenyl Compounds; D039821:Monoterpenes; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D010851:Picrates; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; C530890:jasminodiol; D049452:Green Fluorescent Proteins; C097188:polyglutamine; C004931:1,1-diphenyl-2-picrylhydrazyl; C092341:ATXN3 protein, human; D000067699:Ataxin-3; D053148:Caspase 3
ATXN3; Gardenia jasminoides; NFE2L2; Oxidative stress; Spinocerebellar ataxia