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Iridoids from Scrophularia buergeriana attenuate glutamate‐induced neurotoxicity in rat cortical cultures
Author(s) -
Kim So Ra,
Koo Kyung Ah,
Sung Sang Hyun,
Ma Choong Je,
Yoon Jeong Seon,
Kim Young Choong
Publication year - 2003
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10828
Subject(s) - neuroprotection , neurotoxicity , glutamate receptor , pharmacology , glutathione , kainic acid , oxidative stress , nmda receptor , excitotoxicity , chemistry , biology , biochemistry , toxicity , receptor , organic chemistry , enzyme
Abstract In previous work, we isolated 7 neuroprotective iridoid glycosides from the 90% MeOH fraction of Scrophularia buergeriana (Scrophulariaceae). We therefore investigated the mode of action of 8‐ O‐E‐p ‐methoxycinnamoyl‐harpagide (8‐MCA‐Harp), the most potent neuroprotective iridoid, and its aglycone, harpagide (Harp) using primary cultures of rat cortical cells in vitro. 8‐MCA‐Harp only revealed its neuroprotective activity in a pretreatment paradigm; this iridoid had more selectivity in protecting neurons against N ‐methyl‐ D ‐aspartate (NMDA)‐induced neurotoxicity as opposed to that induced by kainic acid (KA). On the other hand, Harp exerted significant neuroprotective activity when it was administered either before or after glutamate insult and protected cultured neuronal cells from neurotoxicity induced by NMDA or KA. Furthermore, Harp significantly prevented the decrease of glutathione, an antioxidative compound in the brain, in our cultures. Finally, 8‐MCA‐Harp and Harp could successfully reduce the overproduction of nitric oxide and the level of cellular peroxide in cultured neurons. Collectively, these results suggested that Harp and 8‐MCA‐Harp protected primary cultured neurons against glutamate‐induced oxidative stress primarily by acting on the antioxidative defense system and on glutamatergic receptors, respectively. © 2003 Wiley‐Liss, Inc.