Role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the action of ginsenoside Rh2 against beta-amyloid-induced inhibition of rat brain astrocytes.
Ginsenoside, the active principles in Panax ginseng root, has been demonstrated to show neurotrophic and neuroprotective actions for prevention of neuron degeneration. Deposition of beta-amyloid peptide (Abeta) causes neurotoxicity through the formation of plaques in brains with Alzheimer's disease. Pituitary adenylate cyclase-activating polypeptide (PACAP) is introduced as a neurotrophic factor to promote cell survival. However, effect of Rh2, one of ginsenosides, on PACAP expression induced by Abeta remains unclear. In the present study, we found that Rh2 stimulates PACAP gene expression and cell proliferation in type I rat brain astrocytes (RBA1) cells and both effects were not modified by the estrogen antagonists (MPP or ICI 182780). Also, Rh2 ameliorates the RBA1 growth inhibition of Abeta. Moreover, blockade of PACAP receptor PAC1 using PACAP (6-38) inhibits all the actions of Rh2. These results suggest that Rh2 can induce an increase of PACAP to activate PAC1, but not estrogen receptor, and thereby leads to attenuate Abeta-induced toxicity. Thus, ginseng seems useful in the prevention of dementia.
Shieh
Po-Chuen
PC
Department of Pharmacy, Tajen University, Yen-Pou, Ping Tung Shien 90701, Taiwan, ROC.
Tsao
Chiung-Wen
CW
Li
Jin-Shiou
JS
Wu
Hung-Tsung
HT
Wen
Ya-Ju
YJ
Kou
Dai-Huang
DH
Cheng
Juei-Tang
JT
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004965:Estrogen Antagonists / Q000494:pharmacology; D036145:Ginsenosides / Q000494:pharmacology* / Q000627:therapeutic use; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000187:drug effects / Q000378:metabolism*; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016229:Amyloid beta-Peptides; D004965:Estrogen Antagonists; D036145:Ginsenosides; D018696:Neuroprotective Agents; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011960:Receptors, Estrogen; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; C055305:ginsenoside Rh2