Inhibition of YAP-c-Myc signaling pathway involved effect of ORI on anti-glioma / 中国药理学通报

Aim To investigate the effects of oridonin on proliferation, migration and apoptosis of U87 glioma cells and to explore the involvement of the mechanism in the inhibition of Yes-associated protein (YAP)-c - Myc signaling pathway. Methods The effect of oridonin on U87 viability was measured by MTT assay; the migration and invasiveness of cells were measured by transwell assays; the apoptotic rates of cells were assessed by flow cytometry; the caspase-3, B c l - 2, Bax, YAP, c - MycmRNA expression in U87 glioma cells was detected by real-time quantitative P C R; the caspase-3, Bcl-2, Bax, YAP, p-YAP (Seri 27), c-Myc protein expressions were detected by Western blot. Results The proliferation of U87 cells was significantly inhibited by oridonin in a dose-dependent manner (P < 0. 05), and the ability of cell migration and invasion was weakened (P <0. 01), cell apoptosis rate in flow cytometry analysis increased significantly (P <0. 01), the protein and mRNA expression of caspase-3 increased (P < 0. 05), the mRNA and protein expression of Bcl-2/Bax decreased (P < 0. 05), the mRNA and protein expression of Y A P and c-Myc decreased (P < 0. 05), and the protein expression of p - Y A P increased (P < 0. 05). Conclusions Oridonin can significantly inhibit the proliferation and migration of U87 glioma cells and promote the transformation apoptosis of glioma cells; the mechanism may be related to the inhibition of YAP-c-Myc signaling pathway.

Transcranial direct current stimulation promotes hippocampal neurogenesis in mice with cerebral ischemia involving up-regulation of nmda receptors / 中国药理学通报

Aim To investigate the improving effect of transcranial direct current stimulation (tDCS) on endogenous hippocampal neurogenesis in mice with cerebral ischemiaand the possible mechanism. Methods The model of acute cerebral ischemia in mice was established by bilateral common carotid artery occlision (BCCAO). The pathological changes of mice were detected by hippocampal HE staining. The learning and memory function of mice was assessed by Morris water maze. The number of BrdU, DCX and BrdU/NeuN-positive cells was observed through immunofluorescence staining for detecting hippocampal neurogenesis. The mRNA and protein expressions of NMDAR subunits NR2a and NR2b in hippocampus were detected by qRT-PCR and Western blot. Results The neuronal damage in the hippocampal CA1 region was marked (P <0. 01), and the learning and memory function significantly decreased (P<0. 01) in cerebral ischemia mice, suggesting the successful establishment of cerebral ischemia model. At the same time, the number of BrdU, DCX and BrdU/NeuN positive cells was up-reg-ulated significantly (P < 0. 01 ) , indicating the occurrence of neurogenesis in hippocampus after cefebral ischemia. Treatment with tDCS significantly ameliorated the pathological damage in CA1 region of mice, improved learning and memory, and promoted hippocam-pal neurogenesis. Meanwhile, the mRNA and protein expression levels of NR2a and NR2b in hippocampus were also up-regulated (P < 0. 05 or P < 0.01). Conclusions tDCS can promote hippocampal neurogenesis and improve learning and memory function in cerebral ischemia mice, which may be related to theup-regula-tion ofNR2a and NR2b expression.

Gastrodin improves hippocampal neurogenesis by NO-cGMP-PKG signaling pathway in cerebral ischemic mice / 中国中药杂志

This paper was aimed to investigate the effect of gastrodin( GAS) on hippocampal neurogenesis after cerebral was chemic and to explore its mechanism of action related to NO. The cerebral ischemia model of C57 BL/6 mice was established by bilateral common carotid artery occlusion. The pathological changes in hippocampal CA1 region and the cognitive function of mice were assessed by HE staining and Morris water maze test,respectively. The count of Brd U/Neu N positive cells in dentate gyrus was detected by immunofluorescence assay. The NOS activity and the NO content were determined by colorimetric and nitrate reduction methods,respectively.The level of c GMP was measured by ELISA kit,and the PKG protein expression was tested by Western blot. On postoperative day 8,the hippocampal CA1 pyramidal neurons of mice showed irregular structure,with obvious nuclear pyknosis,loose cell arrangement and obvious decrease in the number of neurons. On postoperative day 29,the spatial learning ability and memory were decreased. These results indicated cerebral ischemia in mice. Meanwhile,the Brd U/Neu N positive cells were increased significantly in ischemic mice,indicating that neurogenesis occurred in hippocampus after cerebral ischemia. Treatment with different doses of gastrodin( 50 and 100 mg·kg-1) significantly ameliorated the pathological damages in the CA1 region,improved the ability of learning and memory,and promoted hippocampal neurogenesis. At the same time,both the NOS activity and the NO concentration were decreased in model group,but the c GMP level was increased,and the PKG protein expression was up-regulated. Gastrodin administration activated the NOS activity,promoted NO production,further increased c GMP level and up-regulated PKG protein expression. These results suggested that gastrodin can promote hippocampal neurogenesis after cerebral ischemia and improve cognitive function in mice,which may be related to the activation of NO-cGMP-PKG signaling pathway.