Pedicularioside A from Buddleia lindleyana inhibits cell death induced by 1-methyl-4-phenylpyridinium ions (MPP+) in primary cultures of rat mesencephalic neurons.
Parkinson's disease is characterized by the progressive degeneration of midbrain dopaminergic neurons. Buddleia lindleyana is a traditional Chinese herb, commonly called Zui Yu Cao. The purification and identification of pedicularioside A and other phenylethanoid glycosides from this plant have been reported. However, their neuroprotective effects on the 1-methyl-4-phenylpyridinium ion (MPP(+))-induced death of rat mesencephalic neuron primary cultures and the precise mechanism of this protection remains unclear. We used the 3-(4, 5-dimethylthiozol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay for cellular growth to examine the effects of five phenylethanoid glycosides isolated from B. lindleyana, including pedicularioside A, leucosceptoside A, isoacteoside, acteoside, and arenariside, on the viability of mesencephalic neurons treated with MPP(+). Of the compounds tested, pedicularioside A exhibited the greatest degree of protection from MPP(+)-induced cell death. We also observed a marked increase in the number of tyrosine hydroxylase immunoreactive neurons. Pedicularioside A inhibited expression of the caspase-3 gene and cleavage of poly (ADP-ribose) polymerase (PARP) in cultures exposed to MPP(+). Our results suggest that pedicularioside A has a neuroprotective effect to improve the survival of mesencephalic neurons (dopaminergic neurons and non-dopaminergic neurons). The mode of action appears to be the inhibition of caspase-3 gene expression, thereby protecting mesencephalic neurons from MPP(+)-induced cell death.
Li
Yan-Yun
YY
Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Science, Peking University, 38 Xueyuan Road, Haidian District, Beijing, 100083, PR China.
Lu
Jiang-Hai
JH
Li
Quan
Q
Zhao
Yu-Ying
YY
Pu
Xiao-Ping
XP
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity; D000818:Animals; D032861:Buddleja / Q000737:chemistry*; D053148:Caspase 3 / Q000187:drug effects / Q000235:genetics; D016923:Cell Death / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005960:Glucosides / Q000302:isolation & purification / Q000494:pharmacology*; D057888:Iridoid Glucosides; D039823:Iridoids / Q000302:isolation & purification / Q000494:pharmacology*; D008516:Medicine, Chinese Traditional; D008636:Mesencephalon / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D010300:Parkinson Disease / Q000188:drug therapy; D011065:Poly(ADP-ribose) Polymerases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D005960:Glucosides; D057888:Iridoid Glucosides; D039823:Iridoids; D018696:Neuroprotective Agents; C070619:pedicularioside A; D014446:Tyrosine 3-Monooxygenase; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D015655:1-Methyl-4-phenylpyridinium