Protective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1, 4-diol on Aβ-stressed PC12 cells

Abstract

Amyloid beta-protein (Aβ) is involved in the pathogenesis of Alzheimer's disease (AD). Aβ induces free radical production in neuronal cells, leading to oxidative stress and up-regulation of c-Jun N-terminal kinases (JNK), extracellular-signal-regulated kinases (ERK), p38 mitogen-activated protein kinase (MAPK) pathways and pro-apoptotic Bax expression. Sesamin has been shown to have protection to several models of neurodegenerative diseases by its antioxidant and anti-inflammatory properties. In the present study, we examined the neuroprotective effect of a sesamin derivative, 3-bis (3-methoxybenzyl) butane-1,4-diol (BBD) on Aβ1-42 induced cytotoxicity of PC12 cells. Aβ1-42 induced lipid peroxidation, calcium, reactive oxygen species from the PC12 cells. The effect of BBD on these harmful factors and the related signaling pathways were examined by biochemical and western blot assays. The result showed that BBD protected PC12 cells from Aβ1-42 induced cytotoxicity with the increased cell viability and acetylcholine release, and the decreased lactate dehydrogenase, malondialdehyde and calcium release. BBD significantly reduced Aβ-induced JNK, ERK, p38 MAPK pathways and Bax expression in PC12 cells. Therefore the neuroprotective effect of BBD on Aβ-induced cytotoxicity was involved with antioxidant and anti-inflammatory effects. The result would help the development of new CNS drug for protection of AD.

Melandrii Herba Extract Attenuates H2O2-Induced Neurotoxicity in Human Neuroblastoma SH-SY5Y Cells and Scopolamine-Induced Memory Impairment in Mice

“…Moreover, it has been demonstrated that neuronal cells are protected against oxidative stress-induced cell death by antioxidants such as polyphenols and flavonoids [ 13 , 14 ]. Therefore, antioxidants from natural products are thought to be substances capable of protecting normal neuronal cells from the oxidative stress-induced death or damage that leads to aging-related cognitive decline and neurodegenerative diseases [ 9 , 15 , 16 , 17 , 18 ].…”

A systematic review on antioxidant and antiinflammatory activity of Sesame (Sesamum indicum L.) oil and further confirmation of antiinflammatory activity by chemical profiling and molecular docking

“…Its antioxidant effect has a strong correlation with its antiinflammatory action. Sesamin is another prominent compound reported in SO that possesses significant protective effects against oxidative stress in animal model including through ameliorate SOD, GPx, reduction of malondialdehyde and elevated different liver marker, TBARS, and lipid peroxidation as well as reduction of superoxide production (Ahmad et al, ; Chen, Ying, Chen, Zhang, & Zhang, ; Hou, Chang, & Jeng, ; Hsieh et al, ; Jeng & Hou, ; Jnaneshwari et al, ; Nakai et al, ; Tian & Guo, ; Zhang et al, ). In vitro studies of sesamin especially in neuronal cell line (PC12), it showed reduction of reactive oxygen species (ROS) generation especially NO production (Cao et al, ; Duarte, Chenet, de Almeida, Andrade, & de Oliveira, ; Lee et al, ; Yashaswini, Rao, & Singh, ).…”

“…In vitro studies of sesamin especially in neuronal cell line (PC12), it showed reduction of reactive oxygen species (ROS) generation especially NO production (Cao et al, ; Duarte, Chenet, de Almeida, Andrade, & de Oliveira, ; Lee et al, ; Yashaswini, Rao, & Singh, ). However, Hou et al () reported that 10‐μM sesamin derivative, 3‐bis (3‐methoxybenzyl) butane‐1, 4‐diol, inhibits lactate dehydrogenase, lipid peroxidation, and apoptosis as well as increases ACh release and also prevents cell damage, scavenges ROS, and attenuates the elevation of intracellular free Ca 2+ ion on Aβ‐stressed PC12 cells (Hou et al, ). Both the compounds sesamolin and sesaminol reported to exert their antioxidant effect through the reduction of nitric oxide production and inhibit peroxidation although there is only an oxygen bridge difference ( Figure ) in their structure (Hou, Chen, Tzen, & Jeng, ; Kong et al, ; Lee et al, ).…”

Inhibitory Activities of Sesame Seed Extract and its Constituents against β-Secretase

“…Among these, the anti-oxidant effect of sesame has attracted much attention and the active principles were determined to be sesamin and sesamolin [6]. The anti-oxidant activities may lead to the suppressive effect on amyloid β disposition induced by oxidative stress in PC12 cells [7,8,9].…”