Mori Fructus improves cognitive and neuronal dysfunction induced by beta-amyloid toxicity through the GSK-3β pathway in vitro and in vivo.

A growing body of literature supports the concept that antiaging herbs may be potential candidates for use in treating age-related neurodegeneration, including Alzheimer׳s disease (AD). Mori Fructus is a well-known traditional herbal medicine, food, and dietary supplement. This study employed models of amyloid beta (Aβ)-induced AD to investigate the protective effects of Mori Fructus ethanol extract (ME) against age-related disease and cognitive deficits. To examine the protective effect of ME, we measured cell viability, cytotoxicity, and survival in rat primary hippocampal cultures. We performed behavioral tests and histological analysis in mouse models of AD induced by Aβ(25-35) toxicity. To investigate the mechanism underlying the protective effect, we performed western blotting using antibodies against apoptotic markers as well as the nonphosphorylated and phosphorylated forms of Akt, glycogen synthase kinase-3β (GSK-3β), and tau. We also measured apoptotic marker fluorescence intensity. ME significantly attenuated Aβ-induced cell damage, enhanced Akt and GSK-3β phosphorylation, and reduced tau phosphorylation. ME reduced apoptotic markers that were activated by GSK-3β, and reduced reactive oxygen species production. Further, ME decreased the B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X expression ratio, mitochondria depolarization, cytochrome c release from mitochondria, and caspase-3 activation. We confirmed that ME treatment improved cognitive impairment and neuronal cell death induced by Aβ(25-35) toxicity in the mouse hippocampus via its antiapoptotic activity. These results indicate that ME protects cognition and neurons in AD-like models induced by Aβ via reduction of tau phosphorylation and apoptosis through GSK-3β inactivation.

Kim HG ，Park G ，Lim S ，Park H ，Choi JG ，Jeong HU ，Kang MS ，Lee MK ，Oh MS ... -  《-》

Isorhynchophylline treatment improves the amyloid-β-induced cognitive impairment in rats via inhibition of neuronal apoptosis and tau protein hyperphosphorylation.

Xian YF ，Mao QQ ，Wu JC ，Su ZR ，Chen JN ，Lai XP ，Ip SP ，Lin ZX ... -  《-》

Inhibition of glycogen synthase kinase-3β by Angelica sinensis extract decreases β-amyloid-induced neurotoxicity and tau phosphorylation in cultured cortical neurons.

Increasing evidence has shown that β-amyloid (Aβ) induces hyperphosphorylation of tau and contributes to Aβ toxicity. Recently, tau hyperphosphorylation by glycogen synthase kinase-3β (GSK-3β) activation has been emphasized as one of the pathogenic mechanisms of Alzheimer's disease (AD). The phosphoinositide 3 kinase (PI3K)/Akt pathway is known as an upstream element of GSK-3β. The inhibitory control of GSK-3β, via the PI3K/Akt pathway, is an important mechanism of cell survival. In the present study, we investigated the neuroprotective effects of Angelica sinensis (AS), a traditional Chinese herbal medicine, against Aβ(1-42) toxicity in cultured cortical neurons and also the potential involvement of PI3K/Akt/GSK-3β signal pathway. We revealed that AS extract significantly attenuated Aβ(1-42) -induced neurotoxicity and tau hyperphosphorylation at multiple AD-related sites in a dose-dependent manner. Simultaneously, it increased the levels of phospho-Ser(473) -Akt and down-regulated GSK-3β activity by PI3K activation. The neuroprotective effects of AS extract against Aβ(1-42) -induced neurotoxicity and tau hyperphosphorylation were blocked by LY294002 (10 μM), a PI3K inhibitor. In addition, AS extract reversed the Aβ(1-42) -induced decrease in phosphorylation cyclic AMP response element binding protein (CREB), which could be blocked by the PI3K inhibitor. These results suggest that AS-mediated neuroprotection against Aβ toxicity is likely mediated by the PI3K/Akt/GSK-3β signal pathway.

Zhang Z ，Zhao R ，Qi J ，Wen S ，Tang Y ，Wang D ... -  《-》

Amyloid-beta-induced neurotoxicity is reduced by inhibition of glycogen synthase kinase-3.

Koh SH ，Noh MY ，Kim SH 《BRAIN RESEARCH》

TL-2 attenuates β-amyloid induced neuronal apoptosis through the AKT/GSK-3β/β-catenin pathway.

Zhu X ，Wang S ，Yu L ，Yang H ，Tan R ，Yin K ，Jin J ，Zhao H ，Guan D ，Xu Y ... -  《-》