State Key laboratory of Bioactive Substances and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100050, China.
Eur J Pharmacol. 2012 Apr 5;680(1-3):49-54. doi: 10.1016/j.ejphar.2012.01.031. Epub 2012 Feb 4.
Potassium 2-(1-hydroxypentyl)-benzoate (dl-PHPB) has been shown to have potent neuroprotective effects, such as reducing the infarct volume and improving neurobehavioral deficits in the transient focal cerebral ischemic rat model. The present study is to evaluate the neuroprotective effect of dl-PHPB on hydrogen peroxide (H(2)O(2))-induced apoptosis and the possible mechanism in the human neuroblastoma SK-N-SH cells. Our results showed that dl-PHPB significantly attenuated H(2)O(2)-induced cell death, and reduced neuronal apoptosis. Dl-PHPB partially reversed the decrease of B-cell CLL/lymphoma 2 (Bcl-2) protein level induced by H(2)O(2). Furthermore, dl-PHPB inhibited the elevation of pro-apoptotic Bcl-2-associated X protein (Bax) and caspase3, and alleviated the down-regulation of protein kinase C alpha (PKCα). The PKC inhibitor, Calphostin C significantly attenuated the protective effects of dl-PHPB. The findings suggest that dl-PHPB may protect neurons against H(2)O(2)-induced apoptosis by modulating apoptosis-related proteins, and PKC signaling pathway may be involved in the neuroprotection of dl-PHPB.
2-(1-羟戊基)苯甲酸钾（dl-PHPB）已被证明具有很强的神经保护作用，如减少短暂性局灶性脑缺血大鼠模型中的梗死体积和改善神经行为缺陷。本研究旨在评估 dl-PHPB 对过氧化氢（H₂O₂）诱导的人神经母细胞瘤 SK-N-SH 细胞凋亡的神经保护作用及其可能的机制。我们的结果表明，dl-PHPB 显著减轻了 H₂O₂诱导的细胞死亡，并减少了神经元凋亡。dl-PHPB 部分逆转了 H₂O₂诱导的 B 细胞 CLL/淋巴瘤 2（Bcl-2）蛋白水平的降低。此外，dl-PHPB 抑制了促凋亡 Bcl-2 相关 X 蛋白（Bax）和半胱天冬酶 3的升高，并减轻了蛋白激酶 Cα（PKCα）的下调。PKC 抑制剂 Calphostin C 显著减弱了 dl-PHPB 的保护作用。这些发现表明，dl-PHPB 可能通过调节凋亡相关蛋白来保护神经元免受 H₂O₂诱导的凋亡，PKC 信号通路可能参与了 dl-PHPB 的神经保护作用。
