Neuroprotective effects of artemisinin against isoflurane-induced cognitive impairments and neuronal cell death involve JNK/ERK1/2 signalling and improved hippocampal histone acetylation in neonatal rats

作者：Xu, Guang; Huang, Yun-li; Li, Ping-le; Guo, Hai-ming; Han, Xue-ping^*

来源：Journal of Pharmacy and Pharmacology, 2017, 69(6): 684-697.

DOI：10.1111/jphp.12704

• artemisinin
• histone acetylation
• isoflurane
• mitogen-activated protein kinases
• neuroapoptosis

ObjectiveThis study was performed to assess the effect of artemisinin against isoflurane-induced neuronal apoptosis and cognitive impairment in neonatal rats. @@@ MethodsArtemisinin (50, 100 or 200 mg/kg b.wt/day; oral gavage) was administered to separate groups of neonatal rats starting from postnatal day 3 (P3) to postnatal day 21 (P21). On postnatal day 7 (P7), animals were exposed to inhalation anaesthetic isoflurane (0.75%) for 6 h. @@@ Key findingsNeuronal apoptosis following anaesthetic exposure was significantly reduced by artemisinin. Isoflurane-induced upregulated cleaved caspase-3, Bax and Bad expression were downregulated. Western blotting analysis revealed that treatment with artemisinin significantly enhanced the expression of anti-apoptotic proteins (Bcl-2, Bcl-xL, c-IAP-1, c-IAP-2, xIAP and survivin). Artemisinin increased the acetylation of H3K9 and H4K12 while reducing the expression of histone deacetlyases (HDACs) - HDAC-2 and HDAC-3. Isoflurane-induced activation of JNK signalling and downregulated ERK1/2 expression was effectively modulated by artemisinin. General behaviour of the animals in open-field and T-maze test were improved. Morris water maze test and object recognition test revealed better learning, working memory and also better memory retention on artemisinin treatment. @@@ ConclusionsArtemisinin effectively inhibited neuronal apoptosis and improved cognition and memory via regulating histone acetylation and JNK/ERK1/2 signalling.

• 出版日期2017-6
• 单位郑州大学