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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.
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<p><b>OBJECTIVE</b>To study the mechanisms of Danggui Shaoyao San (DSS) on Alzheimer's diseases (AD) focusing on anti-inflammation.</p><p><b>METHOD</b>AD rats were established by intrahippocampal bilateral injection of Abeta1-42 protein. The AD rats were randomly divided into three groups: AD model group, DSS high-dose group, DSS low-dose group. Vehicle group rats were intrahippocampal bilateral injection of solvent with the same dose. The learning ability and memory of rats was investigated in step-down passive avoidance test and Morris water maze test, expression of IL-1beta, IL-6, TNF-alpha mRNA were observed by reverse transcriptase PCR (RT-PCR), levels of NO was measured by colorimetric method and neuron apoptosis in the hippocampus was investigated by tag method of TdT-mediated end-labeling of fragmented DNA (TUNEL).</p><p><b>RESULT</b>DSS significantly reduced the escape latency and increased the time that rats spent in the target quadrant in Morris water maze test, shortened the responsive latency and decreased the error numbers in step-down passive avoidance test, reduced the expression of the IL-1beta, IL-6, TNF-alpha mRNA, and the level of the NO depressed the neuron apoptosis in the hippocampus.</p><p><b>CONCLUSION</b>DSS improving cognition of the rats might be related to attenuate inflammatory reaction and reduce cell apoptosis in the hippocampus.</p>
Subject(s)
Animals , Male , Rats , Alzheimer Disease , Drug Therapy , Anti-Inflammatory Agents , Pharmacology , Apoptosis , Drugs, Chinese Herbal , Pharmacology , Therapeutic Uses , Hippocampus , Pathology , Rats, Sprague-DawleyABSTRACT
Objective To investigate the effect of propofol on the high-voltage-activated calcium currents [ICa(HVA)] in rat hippocampal neurons. Methods Hippocampal neurons were prepared from Wistar rats and cultured. ICa(HVA) was recorded using whole-cell patch clamp technique. Different concentrations of propofol were added to the culture. The effect of propofol on ICa(HVA) Was evaluated. Results ICa(HVA) was inhibited by propofol in 300 μmol/L reduced peak ICa(HVA) by (24±6)%, (33 ±5) %, (36±7)% and(38±3)% respectively with a mean IC50 of 3.8 μmol/L and Hill coefficient of 0.35. Vmax was shifted from (4.0± 2.0) mV to (3.8 ± 1.6) mV. The V1/2 of inactivation curve was shifted from (- 32 ± 5) mV to (- 35 ± 4) mV and the slope factor was 31 ± 5 and 35 ± 6 before and after administration respectively. Conclusion Propofol produces significant inhibition of calcium currents in the central neurons which may partly explain the action of propofol on central nervous system.
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Objective:To study the effects of andrographolide on the expression of IL-18 related cytokines by peripheral blood monocytes.Methods:After treatment of andrographolide in different concentrations on LPS stimulated human peripheral blood mononuclear cells (PBMC) and LPS+IFN-γ/IL-4 activated magnetic bead-sorted monocytes (PBM),the transcription level of IL-18,IL-18BP,IL-18Rα and IL-18Rβ was detected by real-time RT-PCR;and secreted IL-18,IL-18BP and IL-1β,IL-1Rα by PBM was detected with ELISA.Results:Andrographolide regulated the transcription of IL-18 and IL-18BP in a dose-and time-dependent effect.Andrographolide up-regulated the transcription of IL-18BP in LPS stimulated PBMC,and increased the ratio of IL-18BP/IL-18.The ratio of IL-18BP/IL-18 rose from 9.60 to 214 in LPS+IFNγ activated PBM,and IL-1Rα/IL-1β declined from 9 200 to 6 520 in IL-4 activated PBM by andrographolide treatment.Conclusion:Andrographolide can regulate IL-18 related gene transcription and expression in activated peripheral blood monocytes,and inhibit the excessive expression of IL-18 during inflammation.
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AIM: To study the effects of different dose proportioning the danggui-shaoyao powder (DS) on learning and memory and the content of NO in brain in mice. METHODS: The ability of learning and memory was measured by the step-through task and the water maze task. The content of NO in brain was determined referring to the reagent manual. RESULTS: All different dose proportion of DS promoted the memory of normal mice. And only DS 1 (1 5.4) and DS 3 (1 1.34) obviously improved the scopolamine-induced mice passive avoidance handicap, prolonged the latency, and decreased number of errors. DS 3(1 1.34) obviously improved reserpine-induced mice spatial orientation handicap and prolonged the latency; others had no remarkable effect on spatial orientation handicap of mice. And all different dose proportions of DS could reduce the content of NO in the brain of passive avoidance disruption mice induced by scopolamine. CONCLUSION: DS 3 (1 1.34) improves passive avoidance handicap and spatial orientation handicap of mice, and reduced the content of NO in the brain of passive avoidance handicap mice induced by scopolamine. The effect of DS 3(1 1.34) is the best on benefiting memory.
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A reverse phase HPLC-ELSD method for the determination of ginsenoside Rg1 in the rootof Panaa pseudo-ginseng var. notoginseng (Burkill) Hoo et Tseng was reported. Chromatographic condi-tions: Shim-pack CLC-ODS column (6.0 mm×150 mm)； acetonitrile-water (30: 70) as the mobilephase； Shimadzu LC-6A with SEDEX-55 ELSD detector. The method was found to be simple and accuratewith recovery rate of 100. 50％ and RSD= 1.82 %. The established UV spectrophotometric determinationof total saponins in P. pseudo-ginseng var. notoginseng was also tried and gave an accurate result coinci-dental with that of the HPLC results. The recovery rate was 101.50%， and RSD=1. 44%. It seemed thatboth methods can be used reliably for the quality control of P. pseudo-ginseng var. notoginseng.
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AIM: To study the action of Fufang Danpu Decoction(FFDPD) on experimental gastric ulcer in mice. METHODS: The anti-gastric ulcer action of FFDPD was observed on the gastric ulcer induced by water immersion stress,absolute ethyl alcohol,reserpine and pyloric ligation.The effect on gastric secretion in rats was studied by pyloric ligation.The effect on gastrointestinal motility was observed by gastric emptying in mice. The analgesic effect was tested by the hot-plate test. RESULTS: FFDPD markedly inhibited gastric ulcer induced by water immersion stress,absolute ethyl alcohol,reserpine and pyloric ligation.FFDPD significantly inhibited the secretion of gastric acid and pipsin.FFDPD markedly delayed gastric emptying and enhanced hot pain threshold in mice. CONCLUSION: FFDPD may have anti-gastric ulcer effect,in relation to its inhibition of the secretion of gastric juice,of activity of gastric smooth muscle and analgetic effect.