共查询到20条相似文献,搜索用时 46 毫秒
1.
Azita Hajhossein Talasaz Hossein Khalili Yaser Jenab Mojtaba Salarifar Mohammad Ali Broumand Farzad Darabi 《Drugs in R&D》2013,13(3):199-205
Background and Aims
Ischemia following acute myocardial infarction (AMI) increases the level of pro-fibrotic and inflammatory cytokines, including transforming growth factor (TGF)-β and tumor necrosis factor (TNF)-α. N-acetylcysteine (NAC) has therapeutic benefits in the management of patients with AMI. To the best of our knowledge, this is the first study that has evaluated the effect of NAC on TNF-α and TGF-β levels in patients with AMI.Methods
Following confirmation of AMI, 88 patients were randomly administered NAC 600 mg (Fluimucil®, Zambon, Ticino, Switzerland) or placebo orally twice daily for 3 days. For quantification of TGF-β and TNF-α serum levels after 24 and 72 h of NAC or placebo administration, peripheral venous blood (10 mL) samples were collected at these time points.Results
Comparisons between levels of TGF-β and TNF-α after 24 and 72 h within the NAC or placebo groups revealed that there was not any significant difference except for TGF-β levels in the placebo group, which increased significantly over time (p = 0.042). Significant relationships existed between patients’ ejection fraction (p = 0.005) and TGF-β levels.Conclusions
Receiving NAC could prevent TGF-β levels from increasing after 72 h as compared with not receiving NAC. As TGF-β had strong correlations with the ejection fraction, its antagonism seems to be important in the prevention of remodeling. 相似文献2.
Dong-ke Yu Cai-xia Zhang Shuang-shuang Zhao Sheng-hua Zhang Hao Zhang Shi-ying Cai Rong-guang Shao Hong-wei He 《Acta pharmacologica Sinica》2015,36(4):473-482
Aim:
(−)-Epigallocatechin-3-gallate (EGCG) is one of the most abundant polyphenols in green tea with strong antioxidant activity and various therapeutic effects. In this study, we investigated the anti-fibrotic effects of EGCG and underlying mechanisms in bile duct-ligated (BDL) rats and a liver fibrosis model in vitro.Methods:
BDL rats were treated with EGCG (25 mg·kg−1·d−1, po) for 14 d, and then the serum, bile and liver samples were collected. Liver fibrosis was assessed by serum, urine and bile biochemistry analyses and morphological studies of liver tissues. TGF-β1-stimulated human hepatic stellate LX-2 cells were used as a liver fibrosis model in vitro. The expression of liver fibrogenic genes and signaling proteins in the PI3K/Akt/Smad pathway was examined using Western blotting and/or real-time PCR.Results:
In BDL rats, EGCG treatment significantly ameliorates liver necrosis, inflammation and fibrosis, and suppressed expression of the genes associated with liver inflammation and fibrogenesis, including TNF-α, IL-1β, TGF-β1, MMP-9, α-SMA, and COL1A1. In LX-2 cells, application of EGCG (10, 25 μmol/L) dose-dependently suppressed TGF-β1-stimulated expression of COL1A1, MMP-2, MMP-9, TGF-β1, TIMP1, and α-SMA. Furthermore, EGCG significantly suppressed the phosphorylation of Smad2/3 and Akt in the livers of BDL rats and in TGF-β1-stimulated LX-2 cells. Application of , a specific inhibitor of PI3K, produced similar effects as EGCG did in TGF-β1-stimulated LX-2 cells, but co-application of EGCG and LY294002 did not produce additive effects. LY294002Conclusion:
EGCG exerts anti-fibrotic effects in BDL rats and TGF-β1-stimulated LX-2 cells in vitro via inhibiting the PI3K/Akt/Smad pathway. 相似文献3.
Abolfazl Akbari Saeid Amanpour Samad Muhammadnejad Mohammad Hossein Ghahremani Seyed Hamidollah Ghaffari Ahmad Reza Dehpour Gholam Reza Mobini Fatemeh Shidfar Mahdi Abastabar Ahad Khoshzaban Ebrahim Faghihloo Abbas Karimi Mansour Heidari 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2014,22(1):47
Background
Transforming growth factor-β (TGF-β) pathway is involved in primary tumor progression and in promoting metastasis in a considerable proportion of human cancers such as colorectal cancer (CRC). Therefore, blockage of TGF-β pathway signaling via an inhibitor could be a valuable tool in CRC treatment.Methods
To evaluate the efficacy of systemic targeting of the TGF-β pathway for therapeutic effects on CRC, we investigated the effects of a TGβRI (TGF-β receptor 1) or TβRI kinase inhibitor, SD-208, on SW-48, colon adenocarcinoma cells. In this work, in vitro cell proliferation was studied by methyl thiazolyl tetrazolium (MTT) and bromo-2′-deoxyuridine (BrdU) assays. Also, the histopathological and immunohistochemical evaluations were conducted by hematoxylin and eosin, and Ki-67 and CD34 markers were stained, respectively.Results
Our results showed no significant reduction in cell proliferation and vessel formation (170 ± 70 and 165 ± 70, P > 0.05) in treated SW-48 cells with SD-208 compared to controls.Conclusion
Our data suggested that SD-208 could not significantly reduce tumor growth and angiogenesis in human colorectal cancer model at least using SW-48 cells. 相似文献4.
Masoomeh Yosefifard Majid Hassanpour-Ezatti 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2014,22(1)
Background
In this study, neostigmine-loaded electrospun nanofibers were prepared and then their efficacy and duration of analgesic action were studied after epidural administration in rats by repeated tail flick and formalin tests.Methods
The neostigmine poly vinyl alcohol (PVA) nanofibers were fabricated by electrospinning methods. The nanofibers (1 mg) were injected into the lumbar epidural space (L5-L6) of rats (n = 6). Cerebrospinal fluid samples of rats were collected 1, 5 and 24 hours after injection and then were sampled once weekly for 4 weeks. Free-neostigmine concentration was measured in the samples spectrophotometrically. Rat nociceptive responses were evaluated by repeated tail-flick and formalin tests for 5 weeks after the nanofibers (1 mg) injection. Locomotor activity of rats was measured in the open-field at the same period.Results
The cerebrospinal fluid concentration of free neostigmine reached 5 μg/ml five hours after injection and remained constant until the end of the experiments. The tail-flick latency of treated rats was significantly (p < 0.01) increased and remained constant up to 4 weeks. Pain scores of the rats in both phases of formalin test were significantly (p < 0.01) reduced during the same periods, Epidural injection of the nanofibers had no effect on locomotor activity of rats in an open-field.Conclusions
Our results indicate that the neostigmine nanofibers can provide sustained release of neostigmine for induction of prolonged analgesia after epidural administration. High tissue distribution and penetration of the nanofibers in dorsal horn can increase thermal and chemical analgesia duration without altering locomotor activity in rats for 4 weeks. 相似文献5.
Hamid Reza Sadeghnia Faezeh Vahdati Hassani Hamid Sadeghian Maryam Miandehi Farzin Hadizadeh Gholamreza Karimi 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2013,21(1):75
Background
Cyclodextrins (CDs) have been shown to improve physicochemical and biopharmaceutical properties of drugs when low solubility and low safety limit their use in the pharmaceutical field. Recently, a new amphiphilic peptide-substituted-β-CD, hepta-(N-acetyl-Leu-Gly-Leu)-β-CD (hepta-(N-acetyl-LGL)-β-CD), is developed which exhibited good solubility, strong inclusion ability and an appropriate average molecular weight. However, there is limited information available about its toxic effects. This study was designed to evaluate cytotoxic effects of the hepta-(N-acetyl-LGL)-β-CD (50, 200, 400, and 800 μg/ml) on rat pheochromocytoma PC-12 cells.Results
A significant reduction of cell viability with IC50 values of 1115.0 μg/ml, 762.4 μg/ml, and 464.9 μg/ml at 6, 12, and 24 h post-treatment, respectively, as well as increased lipid peroxide levels and DNA damage were observed.Conclusions
In conclusion, hepta-(N-acetyl-Leu-Gly-Leu)-β-CD exhibit significant toxic properties at high concentrations, probably through induction of oxidative stress and genotoxicity. 相似文献6.
Ali Mandegary Arastoo Saeedi Aziz Eftekhari Vahideh Montazeri Elham Sharif 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2013,21(1):28
Background and the purpose of the study
Silymarin, a standardized extract of the milk thistle (Silybum marianum), is believed to exert some of its hepatoprotective effects though inhibition of free radicals and inflammation. In this study the effect of some pro- and anti-inflammatory cytokines and also antioxidant genes polymorphisms on the hepatoprotective effects of silymarin in the occupationally exposed individuals to hydrogen sulfide (H2S) in the sour natural gas refinery was investigated.Methods
We genotyped seven polymorphisms in six genes reported by others as modifiers of oxidative stress (NQO1, mEPXH1, GSTT1 and GSTM1) and inflammation (TNF-α and TGF-β1) for an association in effect of decreasing in liver function tests (LFTs). The LFTs of 77 sour gas refinery workers were measured before and after administration of silymarin (140 mg, three times per day for 1 month).Results
A significant reduction of blood AST, ALT and ALP was observed after 30 days of consumption (p < 0.001). The decreasing effect of silymarin on ALT in the subjects with high producer genotype (A allele carriers) was less than low producers. There were no significant associations between TGF-β1 and the studied genes of oxidative stress pathway and the effectiveness of silymarin.Conclusion
This is the first report about the effectiveness of silymarin in the subjects exposed chronically to H2S. Meanwhile, the modulatory effect of TNF-α on the effectiveness of silymarin might be used for individualize therapy. 相似文献7.
Hasan Fallah Huseini Maryam Sotoudeh Anvari Yaser Tajallizadeh khoob Shahram Rabbani Farshad Sharifi Seyed Masoud Arzaghi Hossein Fakhrzadeh 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2015,23(1)
Background
Previous studies suggest that chemical constituents present in Pinus eldarica Medw (P. eldarica) nut possess antioxidant properties that may positively influence lipid profile.The present study was conducted to evaluate the efficacy of P. eldarica nut on the experimental atherosclerosis development in hypercholesterolemic rabbits.Methods
Forty male 6 months old white New Zealand rabbits (1.8–2 kg) were randomly assigned into five equal groups. One group was kept as control (normal) group, fed on standard rabbit diet and other 4 groups were fed on high cholesterol diet (HCD). Out of four HCD groups one group was kept as control (HCD) and other three groups were treated with different doses (50, 100 and 200 mg/kg/day) of P. eldarica nut for 8 weeks. Percentage of aortic wall area changes as indication of atherosclerosis development and fasting blood cholesterol, LDL, HDL and triglyceride levels were determined in all groups.Results
The results indicate that fasting blood cholesterol and aortic atherosclerotic involvements in 200 mg/kg/day and 100 mg/kg/day P. eldarica nut extract treated groups significantly decreased as compared to the high cholesterol-diet control group.Conclusion
P. eldarica nut lowers blood cholesterol level and aortic atherosclerotic involvement in hypercholesterolemic rabbits. 相似文献8.
Cheng-biao Lu Zhi-hua Wang Yan-hong Zhou Martin Vreugdenhil 《Acta pharmacologica Sinica》2012,33(2):214-220
Aim:
Fast neuronal network oscillation at the γ frequency band (γ oscillation: 30–80 Hz) has been studied extensively in hippocampal slices under interface recording condition. The aim of this study is to establish a method for recording γ oscillation in submerged hippocampal slices that allows simultaneously monitoring γ oscillation and the oscillation-related intracellular events, such as intracellular Ca2+ concentration or mitochondrial membrane potentials.Methods:
Horizontal hippocampal slices (thickness: 300 μm) of adult rats were prepared and placed in a submerged or an interface chamber. Extracellular field recordings were made in the CA3c pyramidal layer of the slices. Kainate, an AMPA/kainate receptor agonist, was applied via perfusion. Data analysis was performed off-line.Results:
Addition of kainate (25–1000 nmol/L) induced γ oscillation in both the submerged and interface slices. Kainate increased the γ power in a concentration-dependent manner, but the duration of steady state oscillation was reduced at higher concentrations of kainate. Long-lasting γ oscillation was maintained at the concentrations of 100–300 nmol/L. Under submerged condition, γ oscillation was temperature-dependent, with the maximum power achieved at 29 °C. The induction of γ oscillation under submerged condition also required a fast rate of perfusion (5–7 mL/min) and showed a fast dynamic during development and after the washout.Conclusion:
The kainite-induced γ oscillation recorded in submerged rat hippocampal slices is useful for studying the intracellular events related to neuronal network activities and may represent a model to reveal the mechanisms underlying the normal neuronal synchronizations and diseased conditions. 相似文献9.
Objective
The objective of this study was to report the serum concentration of lignocaine after pertubation in patients with endometriosis.Design
Prospective observational study.Setting
The study was carried out at a gynaecological outpatient unit in Stockholm, Sweden.Population
Eligible patients had endometriosis with a dysmenorrhoic pain score of >50 mm on a visual analogue scale, and patent fallopian tubes.Methods
Patients with endometriosis (n = 25) were included in the study. The patients received pre-ovulatory pertubations with lignocaine hydrochloride 10 mg (n = 16) or ringer acetate (placebo, n = 9). The procedure comprised passing the study solution through the uterus and the fallopian tubes via an intra-cervical balloon catheter. Serum samples were collected at 0, 5, 15 and 30 min after pertubation.Main Outcome Measures
The serum samples were analysed for the concentration of lignocaine with an LCMS-SIM method.Results
Low levels of lignocaine were detected in the serum samples following pertubation of 10 mg lignocaine hydrochloride. The highest observed concentration was seen after 30 min (mean 0.050 μg/ml), with an individual maximum of 0.124 μg/ml. Maximum concentration (Cmax) and time to Cmax (Tmax) could not be calculated, since the highest values were observed in the 30-min samples, which was the last sample obtained. Lignocaine was not detected after pertubation with placebo.Conclusions
The serum levels of lignocaine following pertubation of 10 mg lignocaine hydrochloride are detectable but low. Lignocaine pertubated through the fallopian tubes reaches the peritoneal cavity and diffuses through the peritoneum into the blood circulation. Pertubation with lignocaine is safe and has no lignocaine-related adverse events. 相似文献10.
John A. Baron Stephen Senn Michael Voelker Angel Lanas Irene Laurora Wolfgang Thielemann Andreas Brückner Denis McCarthy 《Drugs in R&D》2013,13(1):9-16
Background and Objectives
Aspirin is widely used for short-term treatment of pain, fever or colds, but there are only limited data regarding the safety of this use. To summarize the available data on this topic, we conducted a meta-analysis of the published clinical trial literature regarding the gastrointestinal adverse effects of short-term use of aspirin in comparison with placebo and other medications commonly used for the same purpose.Data Sources and Methods
An extensive literature search identified 119,310 articles regarding possible adverse effects of aspirin, among which 23,131 appeared to possibly include relevant data. An automated text-mining procedure was used to score the references for potential relevance for the meta-analysis. The 3,983 highest-scoring articles were reviewed individually to identify those with data that could be included in this analysis. Ultimately, 78 relevant articles were identified that contained gastrointestinal adverse event data from clinical trials of aspirin versus placebo or an active comparator. Odds ratios (ORs) computed using a Mantel–Haenszel estimator were used to summarize the comparative effects on dyspepsia, nausea/vomiting, and abdominal pain, considered separately and also aggregated as ‘minor gastrointestinal events’. Gastrointestinal bleeds, ulcers, and perforations were also investigated.Results
Data were obtained regarding 19,829 subjects (34 % treated with aspirin, 17 % placebo, and 49 % an active comparator). About half of the aspirin subjects took a single dose. Aspirin was associated with a higher risk of minor gastrointestinal events than placebo or active comparators: the summary ORs were 1.46 (95 % confidence interval [CI] 1.15–1.86) and 1.81 (95 % CI 1.61–2.04), respectively. Ulcers, perforation, and serious bleeding were not seen after use of aspirin or any of the other interventions.Conclusions
During short-term use, aspirin is associated with a higher frequency of gastrointestinal complaints than other medications commonly used for treatment of pain, colds, and fever. Serious adverse events were not observed with aspirin or any of the comparators.Electronic supplementary material
The online version of this article (doi:10.1007/s40268-013-0011-y) contains supplementary material, which is available to authorized users. 相似文献11.
Glycogen synthase kinase-3 (GSK-3) regulates TGF-β1-induced differentiation of pulmonary fibroblasts
Hoeke A Baarsma Lilian HJM Engelbertink Lonneke J van Hees Mark H Menzen Herman Meurs Wim Timens Dirkje S Postma Huib AM Kerstjens Reinoud Gosens 《British journal of pharmacology》2013,169(3):590-603
Background
Chronic lung diseases such as asthma, COPD and pulmonary fibrosis are characterized by abnormal extracellular matrix (ECM) turnover. TGF-β is a key mediator stimulating ECM production by recruiting and activating lung fibroblasts and initiating their differentiation process into more active myofibroblasts. Glycogen synthase kinase-3 (GSK-3) regulates various intracellular signalling pathways; its role in TGF-β1-induced myofibroblast differentiation is currently largely unknown.Purpose
To determine the contribution of GSK-3 signalling in TGF-β1-induced myofibroblast differentiation.Experimental Approach
We used MRC5 human lung fibroblasts and primary pulmonary fibroblasts of individuals with and without COPD. Protein and mRNA expression were determined by immunoblotting and RT-PCR analysis respectively.Results
Stimulation of MRC5 and primary human lung fibroblasts with TGF-β1 resulted in time- and dose-dependent increases of α-sm-actin and fibronectin expression, indicative of myofibroblast differentiation. Pharmacological inhibition of GSK-3 by SB216763 dose-dependently attenuated TGF-β1-induced expression of these myofibroblasts markers. Moreover, silencing of GSK-3 by siRNA or pharmacological inhibition by CT/CHIR99021 fully inhibited the TGF-β1-induced expression of α-sm-actin and fibronectin. The effect of GSK-3 inhibition on α-sm-actin expression was similar in fibroblasts from individuals with and without COPD. Neither smad, NF-κB nor ERK1/2 were involved in the inhibitory actions of GSK-3 inhibition by SB126763 on myofibroblast differentiation. Rather, SB216763 increased the phosphorylation of CREB, which in its phosphorylated form acts as a functional antagonist of TGF-β/smad signalling.Conclusion and Implication
We demonstrate that GSK-3 signalling regulates TGF-β1-induced myofibroblast differentiation by regulating CREB phosphorylation. GSK-3 may constitute a useful target for treatment of chronic lung diseases. 相似文献12.
Masaharu Hirano Akira Yamashina Kazuhiro Hara Yuji Ikari Masahiro Jinzaki Misako Iino Takuhiro Yamaguchi Mitsunobu Tanimoto Sachio Kuribayashi Landiolol Hydrochloride Study Group 《Drugs in R&D》2014,14(3):185-194
Background
During coronary computed tomography (CT) angiography (CCTA), β-blockers (β-adrenergic receptor antagonists) have commonly been used to lower heart rate and improve image quality.Objectives
The aim of this study was to investigate the image quality-improving effect as well as the heart rate-lowering effect of landiolol hydrochloride (an intravenous short-acting β1-adrenergic receptor antagonist) in CCTA by 16-slice multi-detector CT (MDCT).Methods
A total of 39 subjects suspected of having ischemic cardiac disease and requiring CCTA received 0.125 mg/kg of landiolol hydrochloride to study the efficacy and safety of landiolol hydrochloride in a multicenter open-label clinical study. The endpoint was the diagnosable proportion (proportion of subjects whose coronary stenosis was diagnosable).Results
The diagnosable proportions for the reconstruction images at mid-diastole were 56.0 %. The diagnosable proportions for the optimal reconstruction images were 65.4 %. The mean heart rate-lowering effect was observed soon after administration of landiolol hydrochloride; the peak of the effect was reached in 3–5 min, and the effect wore off in 30 min after completion of administration. The mean heart rate-lowering proportion at that time was −14.46 ± 8.4 %.Conclusions
Landiolol hydrochloride was confirmed to reduce heart rate significantly and rapidly after intravenous injection and this suggests that the study drug is a safe and useful agent for improving the image quality of CCTA by 16-slice MDCT. 相似文献13.
Ying Zhang Xiao-juan Ma Chun-yu Guo Ming-ming Wang Na Kou Hua Qu Hui-min Mao Da-zhuo Shi 《Acta pharmacologica Sinica》2016,37(4):463-472
Aim:
We have shown that a combination of ligustrazine and berberine produces more effective inhibition on platelet activation and inflammatory reactions in rat acute myocardial infarction compared with either agent alone. In this study we evaluated the beneficial effects of a combination of ligustrazine and berberine in a rat model of coronary microembolization (CME).Methods:
SD rats were treated with ligustrazine, berberine, ligustrazine+berberine, or clopidogrel for 2 weeks. When the treatment completed, CME was induced by injection of sodium laurate into the left ventricular, while obstructing the ascending aorta. All rats were intubated for hemodynamic measurements. Blood samples were collected for biochemical analyses, flow cytometry, and ELISAs. Heart tissues were isolated for histopathology and subsequent protein analyses.Results:
Pretreatment with the combination of ligustrazine (27 mg·kg−1·d−1) and berberine (90 mg·kg−1·d−1) significantly improved cardiac function, and decreased myocardial necrosis, inflammatory cell infiltration, microthrombosis and serum CK-MB levels in CME rats. In addition, this combination significantly decreased plasma ET-1 levels and von Willebrand factor, inhibited ADP-induced platelet activation, and reduced TNFα, IL-1β, ICAM-1 and RANTES levels in serum and heart tissues. The protective effects of this combination were more prominent than those of ligustrazine or berberine alone, but comparable to those of a positive control clopidogrel (6.75 mg·kg−1·d−1).Conclusion:
The combination of ligustrazine and berberine significantly improved cardiac function in rat CME model via a mechanism involving antiplatelet and anti-inflammatory effects. 相似文献14.
Background and Purpose
Fibroblast-to-myofibroblast differentiation is associated with scarring, an important issue in corneal surgery. Moxifloxacin (MOX), commonly applied to prevent post-operative infection, would benefit more if it modifies fibroblast-to-myofibroblast differentiation other than antimicrobial activity. Our purpose was to explore whether MOX has anti-fibrotic effect in human corneal fibroblasts (HCFs).Experimental Approach
HCFs were incubated in MOX-containing medium concurrently with TGF-β1 (co-treatment), before (pretreatment) or after (post-treatment) adding TGF-β1. HCF contractility was evaluated with a type I collagen gel contraction assay. Expression of α-smooth muscle actin (α-SMA), Smad2, phospho-Smad2-Ser467, Smad4 and Smad7 was determined by immunoblotting. Formation of α-SMA-positive filaments and distribution of active Smad2 were observed under confocal microscopy. Expression of TGF-β receptor types I (TGFBR1) and II (TGFBR2) was assessed with flow cytometry.Key Results
MOX did not affect gel contractility or α-SMA filament formation in HCFs without TGF-β1 stimulation. MOX did, however, retard HCF-containing gel contractility and α-SMA filament formation following TGF-β1 stimulation in the pretreatment and co-treatment groups but not in the post-treatment group. MOX blocked the expression of Smad2, phospho-Smad2-Ser467 and TGFBR1 under TGF-β1 incubation. Additionally, MOX enhanced Smad7 expression in TGF-β1-incubated HCFs, but did not interfere with TGF-β-triggered Smad2 nuclear translocation or Smad4 expression.Conclusions and Implications
MOX inhibited TGF-β-induced fibroblast-to-myofibroblast differentiation via blocking TGFBR1 and enhancing Smad7 expression. MOX should be used before or during surgery to achieve these effects. These results suggest a de novo mechanism by which MOX participates in corneal wound healing. 相似文献15.
Hwan Hee Lee Seulki Lee Kanghyo Lee Yu Su Shin Hyojeung Kang Hyosun Cho 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2015,23(1)
Background
Cordyceps militaris has been used as a traditional medicine in Asian countries for a long time. Different types of Cordyceps extract were reported to have various pharmacological activities including an anti-cancer effect. We investigated the inhibitory effect of Cordyceps militaris ethanol extract on a human colorectal cancer-derived cell line, RKO.Methods
RKO cells were treated with various concentrations of nucleosides-enriched ethanol extract of Cordyceps militaris for 48 h and cytotoxicity was measured using a CCK-8 assay. Then, xenograft Balb/c nude mice were injected with RKO cells and subsequently orally administered with ethanol extract of Cordyceps militaris every day for 3 weeks to examine the inhibitory effect on tumor growth. Lastly, the effect of Cordyceps militaris on cell cycle as well as apoptosis was measured using flow cytometry. Also, the expression of p53, caspase 9, cleaved caspase-3, cleaved PARP, Bim, Bax, Bak, and Bad were detected using western blot assay.Results
RKO cells were highly susceptible to the ethanol extract of Cordyceps militaris (CME) and the growth of RKO cells-derived tumor was significantly delayed by the treatment of Cordyceps militaris. Cordyceps militaris induced cell cycle arrest in G2/M phase (untreated; 20.5 %, CME 100 μg/ml; 61.67 %, CME 300 μg/ml; 66.33 %) and increased early apoptosis (untreated; 1.01 %, CME 100 μg/ml; 8.48 %, CME 300 μg/ml; 18.07 %). The expression of p53, cleaved caspase 9, cleaved caspase-3, cleaved PARP, Bim, Bak, and Bad were upregulated by the treatment of Cordyceps militaris.Conclusion
Ethanol extract of Cordyceps militaris was highly cytotoxic to human colorectal carcinoma RKO cells and inhibited the growth of tumor in xenograft model. The anti-tumor effect of Cordyceps militaris was associated with an induction of cell cycle arrest and mitochondrial-mediated apoptosis. 相似文献16.
Aim:
To evaluate the antifibrotic effect of telmisartan, an angiotensin II receptor blocker, in bile duct-ligated rats.Methods:
Adult Sprague-Dawley rats were allocated to 3 groups: sham-operated rats, model rats underwent common bile duct ligation (BDL), and BDL rats treated with telmisartan (8 mg/kg, po, for 4 weeks). The animals were sacrificed on d 29, and liver histology was examined, the Knodell and Ishak scores were assigned, and the expression of angiotensin-converting enzyme (ACE) and ACE2 was evaluated with immunohistochemical staining. The mRNAs and proteins associated with liver fibrosis were evaluated using RTQ-PCR and Western blot, respectively.Results:
The mean fibrosis score of BDL rats treated with telmisartan was significantly lower than that of the model rats (1.66±0.87 vs 2.13±0.35, P=0.015). However, there was no significant difference in inflammation between the two groups, both of which showed moderate inflammation. Histologically, treatment with telmisartan significantly ameliorated BDL-caused the hepatic fibrosis. Treatment with telmisartan significantly upregulated the mRNA levels of ACE2 and MAS, and decreased the mRNA levels of ACE, angiotensin II type 1 receptor (AT1-R), collagen type III, and transforming growth factor β1 (TGF-β1). Moreover, treatment with telmisartan significantly increased the expression levels of ACE2 and MAS proteins, and inhibited the expression levels of ACE and AT1-R protein.Conclusion:
Telmisartan attenuates liver fibrosis in bile duct-ligated rats via increasing ACE2 expression level. 相似文献17.
Rasool Haddadi Alireza Mohajjel Nayebi Safar Farajniya Shahla Eyvari Brooshghalan Hamdolah Sharifi 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2014,22(1):38
Background
Neuroinflammation and oxidative stress has been shown to be associated with the development of Parkinson disease (PD). In the present study, we investigated the effect of intraperitoneal (i.p.) administration of silymarin, on 6-OHDA-induced motor-impairment, brain lipid per-oxidation and cerebrospinal fluid (CSF) levels of inflammatory cytokine in the rats.Results
The results showed that silymarin is able to improve motor coordination significantly (p < 0.001) in a dose dependent manner. There was a significant (p < 0.001) increase in MDA levels of 6-OHDA-lesioned rats whereas; in silymarin (100, 200 and 300 mg/kg, i.p. for 5 days) pre-treated hemi-parkinsonian rats MDA levels was decreased markedly (p < 0.001). Furthermore the CSF levels of IL-1β was decreased (p < 0.001) in silymarin (100, 200 and 300 mg/kg) pre-treated rats up to the range of normal non-parkinsonian animals.Conclusion
We found that pre-treatment with silymarin could improve 6-OHDA-induced motor imbalance by attenuating brain lipid per-oxidation as well as CSF level of IL-1β as a pro-inflammatory cytokine. We suggest a potential prophylactic effect for silymarin in PD. However, further clinical trial studies should be carried out to prove this hypothesis. 相似文献18.
Fatemeh Attari Maryam Zahmatkesh Hadi Aligholi Shahram Ejtemaei Mehr Mohammad Sharifzadeh Ali Gorji Tahmineh Mokhtari Mojtaba Khaksarian Gholamreza Hassanzadeh 《Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences》2015,23(1)
Background
The beneficial effects of curcumin which includes its antioxidant, anti-inflammatory and cancer chemo-preventive properties have been identified. Little information is available regarding the optimal dose and treatment periods of curcumin on the proliferation rate of different sources of stem cells.Methods
In this study, the effect of various concentrations of curcumin on the survival and proliferation of two types of outstanding stem cells which includes bone marrow stem cells (BMSCs) and adult rat neural stem/progenitor cells (NS/PCs) at different time points was investigated. BMSCs were isolated from bilateral femora and tibias of adult Wistar rats. NS/PCs were obtained from subventricular zone of adult Wistar rat brain. The curcumin (0.1, 0.5, 1, 5 and 10 μM/L) was added into a culture medium for 48 or 72 h. Fluorescent density of 5-bromo-2′-deoxyuridine (Brdu)-positive cells was considered as proliferation index. In addition, cell viability was assessed by MTT assay.Results
Treatment of BMSCs with curcumin after 48 h, increased cell survival and proliferation in a dose-dependent manner. However, it had no effect on NSCs proliferation except a toxic effect in the concentration of 10 μM of curcumin. After a 72 h treatment period, BMSCs and NS/PCs survived and proliferated with low doses of curcumin. However, high doses of curcumin administered for 72 h showed toxic effects on both stem cells.Conclusions
These findings suggest that curcumin survival and proliferative effects depend on its concentration, treatment period and the type of stem cells. Appropriate application of these results may be helpful in the outcome of combination therapy of stem cells and curcumin. 相似文献19.
Tian-ying Xu Xiao-hong Lan Yun-feng Guan Sai-long Zhang Xia Wang Chao-yu Miao 《Acta pharmacologica Sinica》2015,36(4):429-439
Aim:
To investigate the effect of chronic nicotine treatment on vascular function and to identify the underlying mechanisms.Methods:
Adult rats were treated with nicotine (3 mg·kg−1·d−1, sc) for 6 weeks. After the rats were sacrificed, aortic rings were prepared for detecting vascular reactivity, and thoracic aorta and periaortic fat samples were collected for histological and molecular biology studies.Results:
Chronic nicotine treatment significantly reduced periaortic fat, and specifically enhanced smooth muscle relaxation without altering the aortic adventitial fat and endothelium function. Pretreatment with the soluble guanylyl cyclase inhibitor ODQ (3 μmol/L) or PKG inhibitor Rp-8-Br-PET-cGMP (30 μmol/L) abolished the nicotine-induced enhancement of smooth muscle relaxation, whereas the cGMP analogue 8-Br-cGMP could mimic the nicotine-induced enhancement of smooth muscle relaxation. However, the chronic nicotine treatment did not alter PKG protein expression and activity in aortic media.Conclusion:
Chronic nicotine treatment enhances vascular smooth muscle relaxation of rats via activation of PKG pathway. 相似文献20.
Elisa Cairr?o Ezequiel Alvarez Jo?o Miguel Carvas Antonio Jose Santos-Silva Ignacio Verde 《Acta pharmacologica Sinica》2012,33(5):615-624