Epicatechin isolated from Tripterygium wilfordii extract reduces tau-GFP-induced neurotoxicity in zebrafish embryo through the activation of Nrf2.
Tau plays important roles in the assembly and stabilization of the microtubule structure to facilitate axonal transport in mammalian brain. The intracellular tau aggregates to form paired helical filaments leading to neurodegenerative disorders, collectively called tauopathies. In our previous report, we established a zebrafish model to express tau-GFP to induce neuronal death, which could be directly traced in vivo. Recently, we used this model to screen 400 herbal extracts and found 45 of them to be effective on reducing tau-GFP-induced neuronal death. One of the effective herbal extracts is the Tripterygium wilfordii stem extract. HPLC analysis and functional assay demonstrated that epicatechin (EC) is the major compound of Tripterygium wilfordii stem extract to decrease the neurotoxicity induced by tau-GFP. Using a luciferase reporter assay in the zebrafish, we confirmed that EC could activate Nrf2-dependent antioxidant responses to significantly increase the ARE-controlled expression of luciferase reporter gene. These data suggest that EC from the Tripterygium wilfordii stem extract could diminish tau-GFP-induced neuronal death through the activation of Nrf2.
Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan; Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
Bo-Kai
BK
Wu
Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan.
Rey-Yue
RY
Yuan
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.
Yen-Pu
YP
Chang
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan.
Huang-Wei
HW
Lien
Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 31040, Taiwan.
Ting-Shou
TS
Chen
Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 31040, Taiwan.
Hung-Chi
HC
Chien
Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 31040, Taiwan.
Tien-Soung
TS
Tong
Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 31040, Taiwan.
Hui-Ping
HP
Tsai
Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 31040, Taiwan.
Cheng-Li
CL
Fang
Institute of Cellular and Organismic Biology, Academia Sinica, Taipei 115, Taiwan.
Yung-Feng
YF
Liao
Institute of Biotechnology, National Taiwan University, Taipei 106, Taiwan; Department of Entomology, National Taiwan University, Taipei 106, Taiwan. Electronic address: chunche@ntu.edu.tw.
Chun-Che
CC
Chang
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan; Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan. Electronic address: pyc@gate.sinica.edu.tw.
Rita P-Y
RP
Chen
Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan; Institute of Biochemical Sciences, National Taiwan University, Taipei 106, Taiwan. Electronic address: cjibc@gate.sinica.edu.tw.
Chang-Jen
CJ
Huang
D000818:Animals; D002392:Catechin / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D018696:Neuroprotective Agents / Q000008:administration & dosage; D010936:Plant Extracts / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029757:Tripterygium / Q000737:chemistry*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D010936:Plant Extracts; D011993:Recombinant Fusion Proteins; D029961:Zebrafish Proteins; C495638:nfe2l2a protein, zebrafish; D016875:tau Proteins; D049452:Green Fluorescent Proteins; D002392:Catechin
Epicatechin; Neurotoxicity; Nrf2; Tauopathy; Tripterygium wilfordii; Zebrafish