ABSTRACT
Shouwu is a traditional Chinese medicine (TCM) with neuroprotective effect. Shouwu Yizhi decoction (SYD) was designed based on TCM theory. However, little is known about the roles of SYD in Vascular dementia (VaD). The present study aimed to evaluate the potential effects of SYD on the vascular cognitive impairment and explore the underlying mechanism by establishing focal cerebral ischemia/reperfusion (I/R) rat model to induce VaD. SYD administration (54 mg·kg) for 40 days obviously improved the vascular cognitive impairment in the middle cerebral artery occlusion (MCAO) rats as evidenced by the declined neurological deficit score and shortened escape latency via neurological deficit assessment and Morris water maze test. Moreover, SYD decreased neuron damage-induced cell death and ameliorated the ultrastructure of endothelial cells in the MCAO rats, thereby alleviating VaD. Mechanistically, SYD caused increases in the expression of vascular endothelial growth factor (VEGF), CD34 and CD31, compared with the MCAO rats in coronal hippocampus. Simultaneously, the expression level of miR-210 was elevated significantly after SYD administration, compared with the vehicle rats (P < 0.01). The expression of Notch 4 at both mRNA and protein levels was upregulated remarkably along with the notably downregulated DLL4 expression under SYD administration compared with the vehicle rats (P < 0.05). Overall, the above results indicated that SYD promoted angiogenesis by upregulating VEGF-induced miR210 expression to activate Notch pathway, and further alleviated neuron damage and ameliorated the ultrastructure of endothelial cells in the MCAO rats, ultimately enhancing the cognition and memory of MCAO rats. Therefore, our findings preliminarily identified the effect and the mechanism of action for SYD on VaD in rats. SYD could be a potential candidate in treatment of VaD.
Subject(s)
Animals , Humans , Male , Rats , Angiogenesis Inducing Agents , Dementia, Vascular , Drug Therapy , Genetics , Metabolism , Psychology , Drugs, Chinese Herbal , Intracellular Signaling Peptides and Proteins , Genetics , Metabolism , Membrane Proteins , Genetics , Metabolism , Memory , Neuroprotective Agents , Rats, Wistar , Receptor, Notch4 , Genetics , Metabolism , Vascular Endothelial Growth Factor A , Genetics , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To explore the effect of peimine on excision repair cross-complementation 1 (ERCC1) mRNA and lung resistant protein (LRP) expressions in A549/cisplatin (DDP) multidrug resistance (MDR) cell line.</p><p><b>METHODS</b>Lung cancer A549/DDP cells were cultured in vitro.Cells at logarithmic growth phase were divided into 4 groups, i.e., the blank control group, the DDP group, the ligustrazine group (DDP+ligustrazine), the peimine group (DDP + peimine). After 48-h drug action, ERCC1 mRNA expression was detected by RT-PCR and LRP expression detected by cell immunofluorescence.</p><p><b>RESULTS</b>There was no statistical difference in expression levels of ERCC1 mRNA and LRP between the DDP group and the blank control group (P > 0.05). Compared with the DDP group, expression levels of ERCC1 mRNA and LRP obviously decreased in the ligustrazine group and the peimine group (P < 0.05). They were obviously lower in the peimine group than in the ligustrazine group (P < 0.05).</p><p><b>CONCLUSIONS</b>Peimine could reverse MDR of A549/DDP cell line. Its mechanism might be associated with down-regulating ERCC1 mRNA and LRP expression levels.</p>
Subject(s)
Humans , Cell Line, Tumor , Cevanes , Pharmacology , Cisplatin , DNA-Binding Proteins , Genetics , Down-Regulation , Drug Resistance, Multiple , Drug Resistance, Neoplasm , Endonucleases , Genetics , Low Density Lipoprotein Receptor-Related Protein-1 , Genetics , Lung Neoplasms , RNA, Messenger , MetabolismABSTRACT
<p><b>OBJECTIVE</b>This study investigates the efficacy and tolerability of capecitabine plus thalidomide in patients with advanced pancreatic cancer who previously underwent gemcitabine-based therapy.</p><p><b>METHODS</b>Sixty-one patients with unresectable or metastatic PC who had progressed on single-agent Gem or a Gem-containing regimen were enrolled. The patients were randomly divided into two groups. One group (31 patients) was treated with capecitabine alone, and another group was treated with capecitabine plus thalidomide. Capecitabine was administered orally twice a day at a dose of 1, 250 mg/m(2) for 14-day followed by 7-day rest and oral thalidomide 100 mg was given daily without interruption until disease progression or occurrence of unacceptable toxicity.</p><p><b>RESULTS</b>The PFS was 2.8 months (95%CI 2.4 - 3.2) vs. 3.1 months (95%CI 2.6-3.6, P < 0.05) and the OS was 6.1 months (95%CI 5.3 - 6.9) vs. 6.3 months (95%CI 5.2 - 7.4, P = 0.426). In the capecitabine alone group, one patient experienced a partial response (PR), 10 patients showed stable disease (SD) and 20 patients had progressive disease (PD). The another group, two patients experienced a partial response (PR), 11 patients SD, and 17 patients PD. The disease control rates were 35.5% and 43.3%, respectively. The major adverse reaction in the two groups was grade 3 diarrhea.</p><p><b>CONCLUSION</b>Capecitabine plus thalidomide regimen is marginally effective and well tolerated in the second-line setting in patients with gemcitabine-refractory advanced pancreatic cancer.</p>