ABSTRACT
Aim To study and verify the effeet and po¬tential mechanism of punicalagin ( Pun) in the treat-ment of depression by preliminary experiments based on network pharmacology.Methods The intersection genes of Pun and depression were obtained through the database, and protein interaction ( PPI ), GO and KEGG were enriched and analyzed.Molecular docking technology was used to preliminarily verify the binding ability of Pun active components to core therapeutic targets.The depression model of CUMS mice was es¬tablished by chronic stress, and Pun was administered by gavage.Open field experiments were conducted to investigate behavior changes.The content of neuro¬transmitters in hippocampus was detected by liquid chromatography-mass spectrometry ( LC-MS / MS ).Results The results of network pharmacology showed that Pun had 76 targets involved in the occurrence of depression, and PPI network showed that the intersec¬tion genes were closely related.Proteoglycans, lipids and atherosclerosis enriched in cancer.The results of molecular docking showed that there was a good bind¬ing between the compound and the target protein.The results of animal experiments showed that Pun could in¬crease the exploration desire of open field experimental mice.The levels of DA and 5-HT in hippocampus in-creased ( P < 0.05, P < 0.01 ).Conclusions Pun can significantly reduce the depressive state of mice, and its mechanism may act on ALB and AKT1 targets, mediate proteoglycans, lipids and atherosclerotic path¬ways in cancer, so as to improve the secretion of neu¬rotransmitters.
ABSTRACT
Objective To investigate the expression, function and significance of long non-coding RNA (lncRNA) CASC19 in colorectal cancer (CRC). Methods Real-time quantitative polymerase chain reaction was employed to determine the expression of CASC19 in 40 paired samples from CRC surgical specimens and 5 CRC cell lines. The correlations of CASC19 expression with clinicopathologic parameters were analyzed. Transwell assay was applied to detect the migration ability of CRC cells after the CASC19 expression was knocked down by small interfering RNA. Results The expression of CASC19 in colorectal cancer was significantly higher than those in adjacent normal mucosa tissues (t=5.527, P<0.000 1) and was associated with metastasis (P=0.044). Knockdown of CASC19 expression in CRC inhibited the migration ability of CRC in vitro. Conclusions The expression of CASC19 increases in CRC. CASC19 expression is not associated with age, gender, or tumor site/differentiation but with tumor size, lymph node metastasis, and distant metastasis, suggesting high CASC19 expression may promote CRC metastasis.
ABSTRACT
This study was to investigate the effect of peoniflorin on the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream signal molecules in the hippocampus of Alzheimer's disease (AD) rats for exploring the mechanism of peoniflorin protecting hippocampal neurons. AD model rats were established by bilateral intrahippocampal injection of beta-amyloid(1-42) (Abeta(1-42)) and divided randomly into 3 groups: AD model group, peoniflorin low-dose (15 mg x kg(-1)) group and peoniflorin high-dose (30 mg x kg(-1)) group. The vehicle control rats were given bilateral intrahippocampal injection of solvent with the same volume. After peoniflorin or saline was administered (ip) once daily for 14 days, the hippocampuses of all animals were taken out for measuring the expressions of Nrf2, heme oxygenase-1 (HO-1) and gamma-glutamylcysteine synthethase (gamma-GCS) mRNA by reverse transcription PCR, determining the contents of glutathione (GSH), malondialdehyde (MDA) and carbonyl protein (CP) using colorimetric method, and for assaying the expressions of neuronal apoptosis inhibitory protein (NAIP) and Caspase-3 by immunohistochemical staining method. The results showed that peoniflorin markedly increased the expressions of Nrf2, HO-1 and gamma-GCS mRNA, enhanced the level of GSH and decreased the contents of MDA and CP in the hippocampus, as compared with the model group. Peoniflorin also improved the NAIP expression and reduced the Caspase-3 expression in the hippocampus neurons. In conclusion, peoniflorin protects against the Abeta(1-42)-mediated oxidative stress and hippocampal neuron injury in AD rats by activating the Nrf2/ARE pathway.
Subject(s)
Animals , Male , Rats , Alzheimer Disease , Metabolism , Amyloid beta-Peptides , Anti-Inflammatory Agents, Non-Steroidal , Pharmacology , Caspase 3 , Metabolism , Glucosides , Pharmacology , Glutamate-Cysteine Ligase , Genetics , Metabolism , Glutathione , Metabolism , Heme Oxygenase (Decyclizing) , Genetics , Metabolism , Hippocampus , Metabolism , Malondialdehyde , Metabolism , Monoterpenes , Pharmacology , NF-E2-Related Factor 2 , Genetics , Metabolism , Neuronal Apoptosis-Inhibitory Protein , Metabolism , Neurons , Metabolism , Oxidative Stress , Peptide Fragments , RNA, Messenger , Metabolism , Random Allocation , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To investigate the protective effect of paeonol on amyloid beta1-42 (Abeta1-42)-induced neurotoxicity and its mechanism.</p><p><b>METHOD</b>Hippocampal neurons of well-grown newborn SD rats and differentiated SH-SY5Y cell lines were cultured with various concentrations of paeonol (1, 5, 10 micromol x L(-1), respectively) for 6 hours and then incubated with Abeta1-42 oligomer (30 micromol x L(-1)) for 24 hours and 48 hours, respectively. The neuron apoptosis was observed by Heochst33258. Annexin V/PI double stain flow cytometry assay was adopted for determining SH-SY5Y cell apoptosis rate. And the expression of BDNF and Bcl-2 mRNA was detected by RT-PCR.</p><p><b>RESULT</b>Compared with the model group, various concentrations of paeonol (1, 5, 10 micromol x L(-1)) significantly reduced the hippocampal neurons karyopycnosis, decreased the rate of SH-SY5Y cell apoptosis to 22.4%, 18.1% and 16.4%, respectively, and improved the expressions of BDNF and Bcl-2 mRNA.</p><p><b>CONCLUSION</b>Paeonol relieves Abeta1-42 oligomer-induced neuron injury by increasing BDNF and Bcl-2 expressions.</p>