Luo Qingyi, Hu Weiyan, Yu Haofei, Zhang Rongping, Chen Xinglong
Department of Imaging, Yanan Hospital of Kunming City, The Affiliated Hospital of Kunming Medical University, Kunming 650051, Yunnan Province, China.
Yunnan Province Key Laboratory of Cardiovascular Diseases, Kunming 650051, Yunnan Province, China.
Evid Based Complement Alternat Med. 2022 May 17;2022:4376812. doi: 10.1155/2022/4376812. eCollection 2022.
Oxidative stress-induced neurotoxicity plays a key role in Alzheimer's disease (AD). 11,12-Diacetyl-carnosol (NO.20), an acetylated derivative of carnosol extracted from rosemary, displays a high antioxidative effect in vitro.
We investigated the neuroprotective effect of NO.20 on HO-induced neurotoxicity in human neuroblastoma SH-SY5Y cells and its possible mechanism.
We found that NO.20 pretreatment (1 M for 1 h) had cytoprotective effects and weakened HO-induced damage in SH-SY5Y cells by reducing viability loss, apoptotic rate, and reactive oxygen species production. In addition, NO.20 inhibited HO-induced mitochondrial dysfunctions: it alleviated mitochondrial membrane potential loss and cytochrome c release, decreased the Bax/Bcl-2 ratio, and reduced caspase-3 expression. NO.20 also downregulated malondialdehyde and upregulated glutathione. Furthermore, NO.20 pretreatment caused the nuclear translocation of the transcription factor NF-E2-related factor 2 (Nrf2), increasing heme oxygenase-1 (HO-1) expression in SH-SY5Y cells. Notably, we found that silencing Nrf2 using small interfering RNA (siRNA) suppressed the NO.20-induced HO-1 expression and abolished the neuroprotective effect of NO.20.
These results demonstrate that NO.20 protects SH-SY5Y cells from HO-induced neurotoxicity by activating the Nrf2/HO-1 pathway. Thus, the neuroprotective and antioxidative stress effects of NO.20 may make it a promising neuroprotective compound for AD treatment.
氧化应激诱导的神经毒性在阿尔茨海默病（AD）中起关键作用。11,12-二乙酰基鼠尾草酸（编号20）是从迷迭香中提取的鼠尾草酸的乙酰化衍生物，在体外具有高抗氧化作用。
我们研究了编号20对人神经母细胞瘤SH-SY5Y细胞中血红素加氧酶（HO）诱导的神经毒性的神经保护作用及其可能机制。
我们发现编号20预处理（1μM处理1小时）具有细胞保护作用，并通过减少活力丧失、凋亡率和活性氧生成来减轻SH-SY5Y细胞中HO诱导的损伤。此外，编号20抑制HO诱导的线粒体功能障碍：它减轻线粒体膜电位丧失和细胞色素c释放，降低Bax/Bcl-2比值，并降低caspase-3表达。编号20还下调丙二醛并上调谷胱甘肽。此外，编号20预处理导致转录因子核因子E2相关因子2（Nrf2）的核转位，增加SH-SY5Y细胞中血红素加氧酶-1（HO-1）的表达。值得注意的是，我们发现使用小干扰RNA（siRNA）沉默Nrf2可抑制编号20诱导的HO-1表达，并消除编号20的神经保护作用。
这些结果表明，编号20通过激活Nrf2/HO-1途径保护SH-SY5Y细胞免受HO诱导的神经毒性。因此，编号20的神经保护和抗氧化应激作用可能使其成为一种有前途的用于AD治疗的神经保护化合物。
