Unexpected Neuroprotective Effects of Loganin on 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Neurotoxicity and Cell Death in Zebrafish.
1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP), which induces the pathological characteristics of Parkinson's disease in rodents, also specifically targets dopaminergic neurons in zebrafish embryos and larvae. Loganin, a traditional Chinese drug, was reported to regulate immune function and possess anti-inflammatory and anti-shock effects. Here, we investigate the role of loganin in MPTP-induced Parkinson-like abnormalities in zebrafish. MPTP treatment-induced abnormal development, in larvae, such as pericardium edema, increased yolk color, yolk sac edema, and retarded yolk sac resorption, as well as defects in brain development. Loganin could block MPTP-induced defects, with little toxicity to the eggs. Results of whole mount in situ hybridization showed loganin prevented the loss of both dopaminergic neurons and locomotor activity, exhibited by larvae treated with MPTP. In addition, loganin significantly rescued MPTP-induced neurotoxicity on PC12 cells, possibly through the suppression of PI3K/Akt/mTOR axis and JNK signaling pathways. In conclusion, loganin blocks MPTP-induced neurotoxicity and abnormal development in zebrafish. J. Cell. Biochem. 118: 615-628, 2017. © 2016 Wiley Periodicals, Inc.
Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
Li
L
Yao
Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
Shi-Xiao
SX
Peng
Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
Yi-Da
YD
Xu
Department of Cell Biology, Shantou University Medical College, Shantou, Guangdong, 515041, People's Republic of China.
Stanley Li
SL
Lin
Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
Yu-Hong
YH
Li
Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
Chun-Jie
CJ
Liu
Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
Hou-De
HD
Zhao
Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
Lin-Fang
LF
Wang
Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
Yan-Qin
YQ
Shen
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D039823:Iridoids / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020267:MPTP Poisoning / Q000196:embryology / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology*; D029961:Zebrafish Proteins / Q000378:metabolism
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D039823:Iridoids; D048670:MAP Kinase Kinase 4; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D029961:Zebrafish Proteins; C546845:mTOR protein, rat; C059516:loganin
LOGANIN; MPTP; NEUROPROTECTION; NEUROTOXICITY; ZEBRAFISH