Neuroprotective effects of Astragaloside IV in 6-hydroxydopamine-treated primary nigral cell culture.
Parkinson's disease (PD) is caused by a progressive degeneration of dopaminergic neurons in the substantia nigra. Oxidative stress and neural degeneration are suggested to be involved in the pathogenesis of Parkinson's disease. In the present study, Astragaloside IV (AS-IV) extracted from the dried root of Astragalus membranaceus, a well-known Chinese medicine used for the treatment of neurodegenerative diseases, was investigated for its capacity to protect dopaminergic neurons in experimental Parkinson's disease. By examining the effect of AS-IV on 6-hydroxydopamine (6-OHDA)-induced loss of dopaminergic neurons in primary nigral culture, we found that AS-IV pretreatment significantly and dose-dependently attenuated 6-OHDA-induced loss of dopaminergic neurons. Neuronal fiber length studies showed that massive neuronal cell death with degenerated neurons was observed in those cultures incubated with 6-OHDA, whereas in AS-IV co-treatments most dopaminergic neurons were seen to be intact and sprouting. In flow cytometric analysis, AS-IV resulted in a marked and dose-dependent rescue in tyrosine hydrolase (TH)-immunopositive cells from 6-OHDA-induced degeneration of dopaminergic neurons. Double immunofluorescence revealed that AS-IV treatment alone at concentrations of 100 and 200 microM increased the level of TH and NOS (nitrite oxide synthase) immunoreactivities; however, the protective effect of AS-IV on TH and NOS immunopositive cells in 6-OHDA treated nigral cell cultures was only seen at a concentration of 100 microM. These findings show that AS-IV can protect dopaminergic neurons against 6-OHDA-induced degeneration. Besides the neuroprotective effect, AS-IV alone promoted neurite outgrowth and increased TH and NOS immunoreactive of dopaminergic neurons. The neuroprotective and neurosprouting effects of AS-IV are specific for dopaminergic neurons and it has therapeutic potential in the treatment of PD.
Chan
Wing-Sai
WS
School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong.
Durairajan
Siva Sundara Kumar
SS
Lu
Jia-Hong
JH
Wang
Yan
Y
Xie
Li-Xia
LX
Kum
Wan-Fung
WF
Koo
Irene
I
Yung
Ken Kin Lam
KK
Li
Min
M
D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004298:Dopamine / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052248:Nitric Oxide Synthase Type I / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000037:antagonists & inhibitors / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000494:pharmacology* / Q000627:therapeutic use; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013565:Sympatholytics / Q000037:antagonists & inhibitors / Q000633:toxicity; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D014446:Tyrosine 3-Monooxygenase / Q000187:drug effects / Q000378:metabolism
D018696:Neuroprotective Agents; D012503:Saponins; D013565:Sympatholytics; D014315:Triterpenes; C052064:astragaloside A; D016627:Oxidopamine; D052248:Nitric Oxide Synthase Type I; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine