[Gamma-Schisandrin inhibits production of amyloid beta-protein 42 in M146L cells].
OBJECTIVE
To investigate the inhibition of amyloid beta-protein 42 (Abeta42) production in M146L cells by gamma-schisandrin.


METHODS
M146L cells which can produce considerable Abeta42 in vitro were treated with gamma-schisandrin (1.67, 5.00 and 15.00 microg x mL(-1)), beta-secretase inhibitor (S4562, 100.00 microg x mL(-1)) and gamma-secretase inhibitor (S2188, 13.68 microg x mL(-1)), separately. Cell counting kit-8 (CCK-8) was used to assess cell viability. Enzyme-linked immunosorbent assay (ELISA) was carried out to determine the amount of Abeta42. Western blotting was used to examine C99, an intermediary product of APP cleaved by beta-secretase. beta-Secretase and gamma-secretase activities were assayed by commercial kits.


RESULTS
The CCK-8 assay indicated that different concentrations of gamma-schisandrin had no neurotoxicity on the cultured M146L. And the ELISA test showed that the amount of Abeta42 secreted by M146L cells treated with gamma-schisandrin (5.00 and 15.00 microg x mL(-1)) decreased obviously as compared with solvent control. The results of Western blotting test indicated that there was no change of C99 contents and beta-secretase activity in gamma-schisandrin treated cells, while gamma-secretase activity decreased obviously.


CONCLUSIONS
gamma-Schisandrin inhibited production of Abeta42 in M146L cells through inhibiting gamma-secretase.
Liu
Wei
W
Neuropharmacological Research Laboratory, College of Pharmacy, Jinan University, Guangzhou 510632, China.
Yu
Rui
R
Wu
Jia-Hua
JH
Luo
Huan-Min
HM
D000544:Alzheimer Disease / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D034242:Cyclooctanes; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017705:Lignans; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011083:Polycyclic Compounds / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D034242:Cyclooctanes; D017705:Lignans; D010446:Peptide Fragments; D011083:Polycyclic Compounds; C075222:amyloid beta-protein (1-42); C015499:schizandrin B; D053829:Amyloid Precursor Protein Secretases