Kyung Ah Koo

Dibenzocyclooctadiene lignans from Schisandra chinensis protect primary cultures of rat cortical cells from glutamate-induced toxicity.

A methanolic extract of dried Schisandra fruit (Schisandra chinensis Baill.; Schisandraceae) significantly attenuated the neurotoxicity induced by L‐glutamate in primary cultures of rat cortical cells. Five dibenzocyclooctadiene lignans (deoxyschisandrin, gomisin N, gomisin A, schisandrin, and wuweizisu C) were isolated from the methanolic extract; their protective effects against glutamate‐induced neurotoxicity were then evaluated. Among the five lignans, deoxyschisandrin, gomisin N, and wuweizisu C significantly attenuated glutamate‐induced neurotoxicity as measured by 1) an inhibition in the increase of intracellular [Ca2+]; 2) an improvement in the glutathione defense system, the level of glutathione, and the activity of glutathione peroxidase; and 3) an inhibition in the formation of cellular peroxide. These results suggest that dibenzocyclooctadiene lignans from Schisandra chinensis may possess therapeutic potential against oxidative neuronal damage induced by excitotoxin.

Iridoids from Scrophularia buergeriana attenuate glutamate-induced neurotoxicity in rat cortical cultures

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.

Pinusolide and 15-methoxypinusolidic acid attenuate the neurotoxic effect of staurosporine in primary cultures of rat cortical cells.

Apoptosis is a fundamental process required for neuronal development but also occurs in most of the common neurodegenerative disorders. In an attempt to obtain an anti‐apoptotic neuroprotective compound from natural products, we isolated the diterpenoids, pinusolide and 15‐MPA, from B. orientalis and investigated their neuroprotective activity against staurosporine (STS) ‐induced neuronal apoptosis. In addition, we determined the anti‐apoptotic mechanism of these compounds in rat cortical cells.

Asiatic acid derivatives enhance cognitive performance partly by improving acetylcholine synthesis

Thirty‐six semi‐synthesized derivatives of asiatic acid were examined to determine if they had cognitive‐enhancing activity in a passive avoidance test. Among the compounds tested, AS‐2, AS‐2–9–006 and AS‐9–006 significantly alleviated scopolamine‐induced memory impairment at doses of 1 and 10 mg kg−1. Furthermore, AS‐2 and AS‐2–9–006 (1 mg kg−1 administered four times daily) enhanced cognitive performance as determined in a water maze test. These three asiatic acid derivatives did not show any significant effect on the learning process in active avoidance tests. AS‐2, AS‐2–9–006 and AS‐9–006 enhanced cholineacetyltransferase activity in a cholinergic neuroblastoma cell line, S‐20Y, in‐vitro. Therefore, AS‐2, AS‐2–9–006 and AS‐9–006 may have therapeutic value in alleviating certain memory impairment observed in dementia.

Oligonucleotide microarray analysis of apoptosis induced by 15‐methoxypinusolidic acid in microglial BV2 cells

Background and purpose:  We conducted a genome wide gene expression analysis to explore the biological aspects of 15‐methoxypinusolidic acid (15‐MPA) isolated from Biota orientalis and tried to confirm the suitability of 15‐MPA as a therapeutic candidate for CNS injuries focusing on microglia.