Shaikh Sohrab A, Muthuraman Arunachalam
Pharmacology Unit, Faculty of Pharmacy, AIMST University, Semeling, Bedong 08100, Kedah, Malaysia.
Pharmaceuticals (Basel). 2023 Jun 1;16(6):828. doi: 10.3390/ph16060828.
Neurovascular dysfunction leads to the second most common type of dementia, i.e., vascular dementia (VaD). Toxic metals, such as aluminium, increase the risk of neurovascular dysfunction-associated VaD. Hence, we hypothesized that a natural antioxidant derived from palm oil, i.e., tocotrienol-rich fraction (TRF), can attenuate the aluminium chloride (AlCl)-induced VaD in rats. Rats were induced with AlCl (150 mg/kg) intraperitoneally for seven days followed by TRF treatment for twenty-one days. The elevated plus maze test was performed for memory assessment. Serum nitrite and plasma myeloperoxidase (MPO) levels were measured as biomarkers for endothelial dysfunction and small vessel disease determination. Thiobarbituric acid reactive substance (TBARS) was determined as brain oxidative stress marker. Platelet-derived growth factor-C (PDGF-C) expression in the hippocampus was identified using immunohistochemistry for detecting the neovascularisation process. AlCl showed a significant decrease in memory and serum nitrite levels, while MPO and TBARS levels were increased; moreover, PDGF-C was not expressed in the hippocampus. However, TRF treatment significantly improved memory, increased serum nitrite, decreased MPO and TBARS, and expressed PDGF-C in hippocampus. Thus, the results imply that TRF reduces brain oxidative stress, improves endothelial function, facilitates hippocampus PDGF-C expression for neovascularisation process, protects neurons, and improves memory in neurovascular dysfunction-associated VaD rats.
神经血管功能障碍导致了第二常见的痴呆类型，即血管性痴呆（VaD）。铝等有毒金属会增加与神经血管功能障碍相关的VaD风险。因此，我们假设从棕榈油中提取的一种天然抗氧化剂，即富含生育三烯酚的组分（TRF），可以减轻大鼠中氯化铝（AlCl）诱导的VaD。大鼠腹腔注射AlCl（150 mg/kg），持续7天，随后进行21天的TRF治疗。通过高架十字迷宫试验进行记忆评估。测量血清亚硝酸盐和血浆髓过氧化物酶（MPO）水平，作为内皮功能障碍和小血管疾病测定的生物标志物。测定硫代巴比妥酸反应物质（TBARS）作为脑氧化应激标志物。使用免疫组织化学鉴定海马体中血小板衍生生长因子-C（PDGF-C）的表达，以检测新生血管形成过程。AlCl导致记忆和血清亚硝酸盐水平显著降低，而MPO和TBARS水平升高；此外，海马体中未表达PDGF-C。然而，TRF治疗显著改善了记忆，提高了血清亚硝酸盐水平，降低了MPO和TBARS，并在海马体中表达了PDGF-C。因此，结果表明TRF可降低脑氧化应激，改善内皮功能，促进海马体中PDGF-C表达以进行新生血管形成过程，保护神经元，并改善神经血管功能障碍相关VaD大鼠的记忆。
