Preventive Effect of 3,3′‐Dimethoxy‐4,4′‐dihydroxystilbene Triazole against Alzheimer's Disease by Inhibition of Neuronal Apoptosis

Abstract

AbstractThe present study investigated 3,3′‐dimethoxy‐4,4′‐dihydroxy‐stilbene triazole (DMDHSB) in vitro for alleviation of β‐amyloid mediated damage to the PC12 neuronal cells. Exposure of PC12 cells to DMDHSB significantly (P<0.05) reversed β‐amyloid induced loss of viability of PC12 cells in dose‐dependent manner. Moreover, DMDHSB exposure significantly (P<0.05) inhibited over production of PGE2 activated by β‐amyloid in PC12 cells. The β‐amyloid promoted higher levels of COX‐2 and NO were also down‐regulated in PC12 cells on exposure to DMDHSB. The exposure to DMDHSB led to a significant (P<0.05) inhibition of β‐amyloid promoted higher expression of iNOS. The β‐amyloid promoted higher release of iNOS was effectively alleviated by DMDHSB exposure in PC12 cells. In DMDHSB exposed PC12 cells, the β‐amyloid promoted elevation of NF‐κB nuclear translocation was effectively prevented compared to the control. It was observed from the docking studies that one‐pose of DMDHSB interacted with COX‐2 protein at binding affinity of −9.6 kcal/mol at 0‐rmsd. Thus, β‐amyloid promoted loss of PC12 cell viability is prevented on DMDHSB exposure through targeting inflammatory response. Therefore, DMDHSB may be developed as therapeutic candidate for investigation in detail against Alzheimer's disease.