Chan Elaine W L, Yeo Emilia T Y, Wong Kelly W L, See Mun L, Wong Ka Y, Yap Jeremy K Y, Gan Sook Y
Institute for Research, Development and Innovation, International Medical University, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur,Malaysia.
School of Pharmacy, International Medical University, Jalan Jalil Perkasa 19, Bukit Jalil, 57000 Kuala Lumpur,Malaysia.
Curr Alzheimer Res. 2021;18(1):80-87. doi: 10.2174/1567205018666210324124239.
In Alzheimer's disease, accumulation of beta amyloid (Aβ) 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.
The present study aimed to investigate neuroprotective properties of PS against Aβ-induced neurotoxicity and to evaluate its potential mechanism of action.
Neuroprotective effects of hexane (HXN), dichloromethane (DCM), ethyl acetate (EA) and methanol (MEOH) extracts from leaves (L) and roots (R) of PS against Aβ-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 Aβ. The neuroprotective effects of PS were studied using cell viability and cellular reactive oxygen species (ROS) assays. The levels of extracellular Aβ 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.
Hexane extracts of PS (LHXN and RHXN) protected SH-SY5Y cells against Aβ-induced neurotoxicity, and decreased levels of extracellular Aβ and phosphorylated tau (pT231). Although extracts of PS inhibited Aβ-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.
These findings suggest that hexane extracts of PS confer neuroprotection against Aβ- 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.
在阿尔茨海默病中，β淀粉样蛋白（Aβ）的积累引发淀粉样蛋白生成和tau蛋白的过度磷酸化，导致神经元细胞死亡。荜茇是马来人用于治疗风湿病、头痛和增强记忆力的传统草药。它具有多种生物学效应，如抗胆碱能、抗炎、抗氧化和抗抑郁样作用。
本研究旨在探讨荜茇对Aβ诱导的神经毒性的神经保护特性，并评估其潜在的作用机制。
在SH-SY5Y人神经母细胞瘤细胞中研究了荜茇叶（L）和根（R）的己烷（HXN）、二氯甲烷（DCM）、乙酸乙酯（EA）和甲醇（MEOH）提取物对Aβ诱导的神经毒性的神经保护作用。细胞先用荜茇预处理24小时，然后用Aβ诱导24小时。使用细胞活力和细胞活性氧（ROS）测定法研究荜茇的神经保护作用。测定细胞外Aβ和苏氨酸231（pT231）磷酸化的tau蛋白水平。分别使用qRT-PCR分析和蛋白质印迹分析评估基因和蛋白质表达。
荜茇的己烷提取物（LHXN和RHXN）保护SH-SY5Y细胞免受Aβ诱导的神经毒性，并降低细胞外Aβ和磷酸化tau（pT231）的水平。虽然荜茇提取物抑制Aβ诱导的ROS产生，但神经保护作用不太可能仅仅归因于荜茇的抗氧化能力。此外，机制研究表明，荜茇的神经保护作用可能是由于其通过下调BACE和APP来调节淀粉样蛋白生成的能力。
这些发现表明，荜茇的己烷提取物通过减弱淀粉样蛋白生成和tau过度磷酸化，对SH-SY5Y细胞中Aβ诱导的神经毒性具有神经保护作用。由于其神经保护特性，荜茇可能是阿尔茨海默病的潜在治疗药物。
