College of Veterinary Medicine, Chungbuk National University, Cheongju 28644, Korea.
Institute for Stem Cell & Regenerative Medicine (ISCRM), Chungbuk National University, Cheongju 28644, Korea.
Nutrients. 2022 Mar 25;14(7):1380. doi: 10.3390/nu14071380.
1,3-Dipalmitoyl-2-oleoylglycerol (POP) is a triacylglyceride found in oils from various natural sources, including palm kernels, sunflower seeds, and rice bran. In the current study, the neuroprotective effects and the specific mechanism of POP derived from rice bran oil were investigated for the first time using the middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats. Orally administered POP at 1, 3, or 5 mg/kg (three times: 0.5 h before MCAO, after 1 h of MCAO, and after 1 h of reperfusion) markedly reduced the MCAO/R-induced infarct/edema volume and neurobehavioral deficits. Glutathione depletion and the oxidative degradation of lipids in the rat brain induced by MCAO/R were prevented by POP administration. The upregulation of phosphorylated p38 MAPKs, inflammatory factors (inducible nitric oxide synthase (i-NOS) and cyclooxygenase-2 (COX-2)), and pro-apoptotic proteins (B-cell lymphoma-2 (Bcl-2) associated X protein (Bax) and cleaved caspase-3) and the downregulation of the anti-apoptotic protein (Bcl-2) in the ischemic brain were significantly inhibited by POP administration. In addition, downregulation of phosphatidylinositol 3'-kinase (PI3K), phosphorylated protein kinase B (Akt), and phosphorylated cyclic (adenosine monophosphate) AMP responsive element-binding protein (CREB) expression in the ischemic brain was inhibited by POP administration. These results suggest that POP might exert neuroprotective effects by inhibition of p38 MAPK and activation of PI3K/Akt/CREB pathway, which is associated with anti-oxidant, anti-apoptotic, and anti-inflammatory action. From the above results, the present study provides evidence that POP might be effectively applied for the management of cerebral ischemia-related diseases.
1,3-二棕榈酰基-2-油酰基甘油（POP）是一种三酰基甘油，存在于各种天然来源的油中，包括棕榈仁、葵花籽和米糠。在目前的研究中，首次使用大鼠大脑中动脉闭塞/再灌注（MCAO/R）模型研究了来源于米糠油的 POP 的神经保护作用及其特定机制。口服给予 1、3 或 5mg/kg 的 POP（三次：MCAO 前 0.5 小时、MCAO 后 1 小时和再灌注后 1 小时）可显著减少 MCAO/R 引起的梗死/水肿体积和神经行为缺陷。POP 给药可预防 MCAO/R 引起的大鼠脑内谷胱甘肽耗竭和脂质氧化降解。POP 给药可显著抑制缺血性脑内磷酸化 p38MAPKs、炎性因子（诱导型一氧化氮合酶（iNOS）和环氧化酶-2（COX-2））和促凋亡蛋白（B 细胞淋巴瘤-2（Bcl-2）相关 X 蛋白（Bax）和 cleaved caspase-3）的上调和抗凋亡蛋白（Bcl-2）的下调。此外，POP 给药还可抑制缺血性脑内磷脂酰肌醇 3'-激酶（PI3K）、磷酸化蛋白激酶 B（Akt）和磷酸化环（腺苷单磷酸）AMP 反应元件结合蛋白（CREB）表达的下调。这些结果表明，POP 可能通过抑制 p38MAPK 和激活 PI3K/Akt/CREB 通路发挥神经保护作用，这与抗氧化、抗凋亡和抗炎作用有关。综上所述，本研究为 POP 可能有效应用于治疗与脑缺血相关疾病提供了证据。
