Piper Sarmentosum Roxb. Attenuates Beta Amyloid (A Beta)-Induced Neurotoxicity Via The Inhibition Of Amyloidogenesis And Tau Hyperphosphorylation In Sh-Sy5y Cells

Background: In Alzheimer's disease, accumulation of beta amyloid (A beta) triggers amyloidogenesis and hyperphosphorylation of tau protein leading to neuronal cell death. Piper sarmentosum Roxb. (PS) is a traditional medicinal herb used by Malay to treat rheumatism, headache and boost memory. It possesses various biological effects, such as anti-cholinergic, anti-inflammatory, anti-oxidant and anti-depressant-like effects.Objective: The present study aimed to investigate neuroprotective properties of PS against A beta-induced neurotoxicity and to evaluate its potential mechanism of action.Methods: Neuroprotective effects of hexane (HXN), dichloromethane (DCM), ethyl acetate (EA) and methanol (MEOH) extracts from leaves (L) and roots (R) of PS against A beta-induced neurotoxicity were investigated in SH-SY5Y human neuroblastoma cells. Cells were pre-treated with PS for 24 h followed by 24 h of induction with A beta. The neuroprotective effects of PS were studied using cell viability and cellular reactive oxygen species (ROS) assays. The levels of extracellular A beta and tau proteins phosphorylated at threonine 231 (pT231) were determined. Gene and protein expressions were assessed using qRT-PCR analyses and western blot analyses, respectively.Results: Hexane extracts of PS (L-HXN and R-HXN) protected SH-SY5Y cells against A beta-induced neurotoxicity, and decreased levels of extracellular A beta and phosphorylated tau (pT231). Although extracts of PS inhibited A beta-induced ROS production, it was unlikely that neuroprotective effects were simply due to the anti-oxidant capacity of PS. Further, mechanistic study suggested that the neuroprotective effects of PS might be due to its capability to regulate amyloidogenesis through the downregulation of BACE and APP.Conclusion: These findings suggest that hexane extracts of PS confer neuroprotection against A beta-induced neurotoxicity in SH-SY5Y cells by attenuating amyloidogenesis and tau hyperphosphorylation. Due to its neuroprotective properties, PS might be a potential therapeutic agent for Alzheimer's disease.