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Xiong Cai - One of the best experts on this subject based on the ideXlab platform.
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effect of Oxymatrine on the replication cycle of hepatitis b virus in vitro
World Journal of Gastroenterology, 2010Co-Authors: Kekai Zhao, Xiong Cai, Xiaohui Miao, Ruiqi Zhang, Junxue WangAbstract:AIM: To determine the antiviral mechanism or target of Oxymatrine against hepatitis B virus (HBV). METHODS: HepG2.2.15 cells were incubated with culture medium containing 500 μg/mL of Oxymatrine for 2 and 5 d. The surface antigen of HBV (HBsAg) and e antigen of HBV (HBeAg) in supernatant were determined by ELISA. HBV DNA in supernatant, and intracellular covalently closed circular DNA (cccDNA), relaxed circular DNA (rcDNA) and pregenomic RNA (pgRNA) were quantified by specific real-time polymerase chain reaction (PCR) or reverse transcription (RT)-PCR. RESULTS: Treatment with Oxymatrine for 2 d and 5 d reduced the production of HBV by the cell line, as indicated by the decline of HBsAg (22.67%, t = 5.439, P = 0.0322 and 22.39%, t = 5.376, P = 0.0329, respectively), HBeAg (55.34%, t = 9.859, P = 0.0101 and 43.97%, t = 14.080, P = 0.0050) and HBV DNA (40.75%, t = 4.570, P = 0.0447 and 75.32%, t = 14.460, P = 0.0047) in the supernatant. Intracellular cccDNA was also markedly reduced by 63.98% (t = 6.152, P = 0.0254) and 80.83% (t = 10.270, P = 0.0093), and intracellular rcDNA by 34.35% (t = 4.776, P = 0.0413) and 39.24% (t = 10.050, P = 0.0097). In contrast, intracellular pgRNA increased by 6.90-fold (t = 8.941, P = 0.0123) and 3.18-fold (t = 7.432, P = 0.0176) after 500 μg/mL of Oxymatrine treatment for 2 d and 5 d, respectively. CONCLUSION: Oxymatrine may inhibit the replication of HBV by interfering with the process of packaging pgRNA into the nucleocapsid, or inhibiting the activity of the viral DNA polymerase.
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capsule Oxymatrine in treatment of hepatic fibrosis due to chronic viral hepatitis a randomized double blind placebo controlled multicenter clinical study
World Journal of Gastroenterology, 2004Co-Authors: Yimin Mao, Hui Wang, Minde Zeng, Mobin Wan, Chengwei Chen, Jiyao Wang, Weimin She, Xiong Cai, Xiaqiu Zhou, Meifang TangAbstract:AIM: To evaluate the efficacy and safety of Oxymatrine capsule in treatment of hepatic fibrosis in patients with chronic viral hepatitis. METHODS: It was a randomized, double blind, placebo-controlled, multicenter clinical study. One hundred and forty-four patients were divided into Oxymatrine capsule group(group A) and placebo group (group B).The course was 52 wk. Patients were visited once every 12 wk and the last visit was at 12 wk after cessation of the treatment. All patients had liver biopsy before treatment. part of them had a second biopsy at the end of therapy. Clinical symptoms, liver function test, serum markers of hepatic fibrosis were tested. Ultrasound evaluation was performed before, during and at the end of therapy. RESULTS: One hundred and forty-four patients enrolled in the study. Of them 132 patients completed the study according to the protocol,49 patients had liver biopsy twice (25 patients in group A and 24 in group B). At the end of therapy, significant improvements in hepatic fibrosis and inflammatory activity based on Semi-quantitative scoring system (SSS) were achieved in group A. The total effective rate of the treatment was 48.00%, much higher than that of 4.17% in group B (P < 0.05). Significant improvement in serum markers of hepatic fibrosis such as hyaluronic acid (HA) and type III procollagenic peptide (P III P) in group A was seen (P < 0.05). The total effective rate of serum markers at the end of therapy in group A was 68.19%, much higher than that of 34.85% in group B (P < 0.05). The total effective rate of noninvasive markers at the end of therapy in group A was 66.67%, much higher than that of 30.30% in group B (P < 0.05). The rate of adverse events was similar in two groups. CONCLUSION: Oxymatrine capsule is effective and safe in treatment of hepatic fibrosis due to chronic viral hepatitis.
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Oxymatrine therapy for chronic hepatitis b a randomized double blind and placebo controlled multi center trial
World Journal of Gastroenterology, 2003Co-Authors: Minde Zeng, Hui Wang, Yimin Mao, Mobin Wan, Chengwei Chen, Jiyao Wang, Weimin She, Xiong Cai, Xiaqiu Zhou, Meifang TangAbstract:AIM: To evaluate the efficacy and safety of capsule Oxymatrine in the treatment of chronic hepatitis B. METHODS: A randomised double-blind and placebo-controlled multicenter trial was conducted. Injection of Oxymatrine was used as positive-control drug. A total of 216 patients with chronic hepatitis B entered the study for 24 wk, of them 108 received capsule Oxymatrine, 36 received injection of Oxymatrine, and 72 received placebo. After and before the treatment, clinical symptoms, liver function, serum hepatitis B virus markers, and adverse drug reaction were observed. RESULTS: Among the 216 patients, six were dropped off, and 11 inconsistent with the standard were excluded. Therefore, the efficacy and safety of Oxymatrine in patients were analysed. In the capsule treated patients, 76.47% became normal in ALT level, 38.61% and 31.91% became negative both in HBV DNA and in HBeAg. In the injection treated patients, 83.33% became normal in ALT level, 43.33% and 39.29% became negative both in HBV DNA and in HBeAg. In the placebo treated patients, 40.00% became normal in ALT level, 7.46% and 6.45% became negative both in HBV DNA and in HBeAg. The rates of complete response and partial response were 24.51% and 57.84% in the capsule treated patients, and 33.33% and 50.00% in the injection treated patients, and 2.99% and 41.79% in the placebo treated patients, respectively. There was no significance between the two groups of patients, but both were significantly higher than the placebo. The adverse drug reaction rates of the capsule, injection and placebo were 7.77%, 6.67% and 8.82%, respectively. There was no statistically significant difference among them. CONCLUSION: Oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.
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effect of Oxymatrine on murine fulminant hepatitis and hepatocyte apoptosis
Chinese Medical Journal, 2002Co-Authors: Xiaoxing Xiang, Guo Jun Wang, Xiong CaiAbstract:Objective To evaluate the protective effects and mechanism of action of Oxymatrine (OM) on the experimental fulminant hepatitis (FH) and early hepatocyte apoptosis in murine liver tissue. Methods Fulminant hepatitis mice were induced by injecting lipopolysaccharide (LPS) intraperitoneally (ip) in galactosamine (GalN) sensitized mice. Two separate experiments were designed, including saline control group, fulminant hepatitis group and Oxymatrine pretreated group (50 mg/kg, intraperitoneally, bid x 3 days). The levels of serum tumor necrosis factor alpha (TNFa) in mice from two experiments were determined at 5-hour and 7.5-hour after injecting galactosamine/lipopolysaccharide. Mouse liver samples at 5-hour time point were obtained for in situ end labeling (ISEL) staining and ultrastructural observation of apoptotic cells under transmission electron microscope (TEM) . Liver samples at 7. 5-hour time point were taken for hematoxylin-eosin (HE) staining and immunohistochemical staining of Fas and its ligand (FasL). Results As compared with the fulminant hepatitis group, the levels of serum tumor necrosis factor alpha in mice from the OM pretreated group at 5-hour and 7.5-hour time point were all significantly decreased ( P < 0.05 and P < 0.01 respectively). Hepatocyte apoptosis in mice at 5-hour time point was significantly inhibited (P < 0.01). Both the degree of liver injury and the degree of Fas and Fas ligand expression in the OM pretreated group were reduced remarkably ( P<0.01 and 0.05 respectively) when compared with the saline control group. Conclusions Oxymatrine protects mice from fulminant hepatitis induced by GalN/LPS and may block hepatocyte apoptosis and subsequent necrosis through downregulating the production of serum tumor necrosis factor alpha and the expression of Fas and Fas ligand in liver tissue.
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inhibition of hepatitis b virus by Oxymatrine in vivo
World Journal of Gastroenterology, 2001Co-Authors: Xiao Song Chen, Guo Jun Wang, Xiong CaiAbstract:AIM: To investigate the anti-HBV effect of Oxymatrine (oxy) in vivo. METHODS: HBV transgenic mice were produced by micro-injection of a 4.2 kb fragment containing the complete HBV genomes. Expression level of HBsAg and HBcAg in the transgenic mice liver was determined by immunohistochemical assay. RESULTS: Four groups (6 mice in each group) were injected intraperitoneally with oxy at the dosage of 100, 200, and 300 mg/kg or with saline once a day for 30 d. Both HBsAg and HBcAg were positive in livers of all the six mice in the control group (injected with saline), and were positive in livers of two mice in 100 mg/kg group and 300 mg/kg group. In 200 mg/kg group, HBsAg and HBcAg were negative in livers of all the six mice. Based on the results, 200 mg/kg is the ideal dosage to explore the effect of oxy at different time points. According to the oxy treatment time, mice were divided into four groups: 10 d, 20 d, 30 d and 60 d (4 mice in each group). Each mouse underwent liver biopsy two weeks before the treatment of oxy. Down-regulation of HBsAg and HBcAg appeared after treatment of Oxymatrine for 10 d and 20 d, Dane-like particles disappeared after the treatment of oxy for 20 d under electron microscopy, however, the expression level of HBsAg and HBcAg returned to normal 60 d later after oxy treatment. CONCLUSION: Oxymatrine can reduce the contents of HBsAg and HBcAg in transgenic mice liver,longer treatment time and larger dosage do not yield better effects.
Sun Hongli - One of the best experts on this subject based on the ideXlab platform.
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antiarrhythmic effects and ionic mechanisms of Oxymatrine from sophora flavescens
Phytotherapy Research, 2010Co-Authors: Cao Yonggang, Li Lei, Liu Yan, Jing Shan, Gao Jingquan, Shen Zhiying, Xing Yan, Wu Mingli, Xu Changqing, Sun HongliAbstract:Accumulating evidence indicates that Oxymatrine may exert protective effects on the cardiovascular system. This study was designed to evaluate the antiarrhythmic effects as well as the electrophysiological properties of Oxymatrine. The antiarrhythmic activity of Oxymatrine was observed in a rat model of arrhythmia induced by coronary ligation. Action potential duration (APD), L-type calcium current (I(Ca-L) ), transient outward potassium current (I(to) ) and inward rectifier potassium current (I(K1)) in rat ventricular myocytes were recorded by utilizing the whole cell patch-clamp technique. The results showed that administration of Oxymatrine significantly delayed the onset of ventricular arrhythmia, decreased the duration of ventricular arrhythmia and reduced the arrhythmia score of arrhythmic rats. The beneficial effects of Oxymatrine may be related to the shortening of APD through reduction of I(Ca-L) , enhancement of I(to) and inhibition of I(K1).
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antiarrhythmic effects and ionic mechanisms of Oxymatrine from sophora flavescens
Phytotherapy Research, 2010Co-Authors: Cao Yonggang, Li Lei, Liu Yan, Jing Shan, Gao Jingquan, Shen Zhiying, Xing Yan, Wu Mingli, Xu Changqing, Sun HongliAbstract:Accumulating evidence indicates that Oxymatrine may exert protective effects on the cardiovascular system. This study was designed to evaluate the antiarrhythmic effects as well as the electrophysiological properties of Oxymatrine. The antiarrhythmic activity of Oxymatrine was observed in a rat model of arrhythmia induced by coronary ligation. Action potential duration (APD), L-type calcium current (ICa-L), transient outward potassium current (Ito) and inward rectifier potassium current (IK1) in rat ventricular myocytes were recorded by utilizing the whole cell patch-clamp technique. The results showed that administration of Oxymatrine significantly delayed the onset of ventricular arrhythmia, decreased the duration of ventricular arrhythmia and reduced the arrhythmia score of arrhythmic rats. The beneficial effects of Oxymatrine may be related to the shortening of APD through reduction of ICa-L, enhancement of Ito and inhibition of IK1. Copyright © 2010 John Wiley & Sons, Ltd.
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cardioprotective effects and underlying mechanisms of Oxymatrine against ischemic myocardial injuries of rats
Phytotherapy Research, 2008Co-Authors: Sun Hongli, Li Lei, Shang Lei, Zhao Dan, Dong Deli, Qiao Guofen, Liu Yan, Chu Wenfeng, Yang BaofengAbstract:Oxymatrine has been demonstrated to have a variety of pharmacological actions. Accumulating evidence indicates that Oxymatrine may exert a protective effect on the cardiovascular system. The study was designed to explore the possible role of Oxymatrine against myocardial ischemic damage and several related signaling pathways as potential mechanisms. The protective properties of Oxymatrine were studied in a rat model of acute myocardial infarction due to permanent ligation of the left anterior descending coronary artery. The results showed that administration of Oxymatrine relieved myocardial injuries during ischemia, and this was achieved by protecting cardiomyocytes from apoptotic death. The beneficial effects of Oxymatrine were likely mediated by an inhibition of lipid peroxidation (MDA production) and an increase in endogenous antioxidant activity (SOD), activation of the survival signaling molecule (Bcl-2), and a reduction of apoptotic mediator (Fas) and intracellular Ca2+ overload. Copyright © 2008 John Wiley & Sons, Ltd.
Kyung Ho Row - One of the best experts on this subject based on the ideXlab platform.
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Row K: Determination of matrine and Oxymatrine in Sophora flavescens ait. Via high performance liquid chromatography
2016Co-Authors: Yong An Jung, Xiaolong Wan, Hongyuan Yan, Kyung Ho RowAbstract:Abstract: In the present work, a reversed phase high performance liquid chromatographic method (HPLC) has been developed and validated for analysis of matrine and Oxymatrine in Sophora Flavescens Ait. HPLC separation of the alkaloids was performed on a C18 column. A mobile phase composed of methanol-water-trifluoroacetic in a ratio of 16:84:0.002 (v=v) was found to be the most suitable mobile phase for this separation. The extracted amounts are 0.0091 and 0.15mg=g and the relative standard deviations were 3.3 % for the matrine and 2.9 % for the Oxymatrine analysis
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selective extraction and separation of Oxymatrine from sophora flavescens ait extract by silica confined ionic liquid
Journal of Chromatography B, 2012Co-Authors: Minglei Tian, Kyung Ho RowAbstract:This study highlighted the application of a two-stepped extraction method for extraction and separation of Oxymatrine from Sophora flavescens Ait. extract by utilizing silica-confined ionic liquids as sorbent. The optimized silica-confined ionic liquid was firstly mixed with plant extract to adsorb Oxymatrine. Simultaneously, some interference, such as matrine, was removed. The obtained suspension was then added to a cartridge for solid phase extraction. Through these two steps, target compound was adequately separated from interferences with 93.4% recovery. In comparison with traditional solid phase extraction, this method accelerates loading and reduces the use of organic solvents during washing. Moreover, the optimization of loading volume was simplified as optimization of solid/liquid ratio.
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solid phase extraction of matrine and Oxymatrine from sophora flavescens ait using amino imidazolium polymer
IEEE Journal of Solid-state Circuits, 2010Co-Authors: Minglei Tian, Kyung Ho RowAbstract:A new, polymer-confined, ionic liquid sorbent was developed by a process involving polymerization and modification. The obtained particles were successfully used as a special sorbent in SPE process to isolate matrine and Oxymatrine from Sophora Flavescens Ait. Different washing and elution solvents, such as ethanol, methanol, acetonitrile and methanol/triethylamine (90:10, v/v), were evaluated. Compared with the C18 and NH2 sorbents, the amino-imidazolium polymer sorbent exhibited higher selectivity. Quantitative analysis was carried out by using a C18 column. The two compounds exhibited good linearity from 5 � 10 � 3 to 0.50 mg/mL (r 2 40.99). The bound amounts between target compounds and proteins were obtained by this sorbent. After three recycles of amino-imidazolium polymer, the extract amounts of the target compounds were not significantly decreased.
Ying Zhang - One of the best experts on this subject based on the ideXlab platform.
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Oxymatrine exerts organ and tissue protective effects by regulating inflammation oxidative stress apoptosis and fibrosis from bench to bedside
Pharmacological Research, 2020Co-Authors: Xu Lan, Junnan Zhao, Ying Zhang, Yao Chen, Yue LiuAbstract:Oxymatrine is a quinazine alkaloid extracted from Sophora flavescens with various therapeutic effects such as organ- and tissue-protective, anti-inflammatory, anti-cancer, and anti-viral effects. In this review, we summarize the protective effects of Oxymatrine on damaged organs and tissues by analyzing both in vivo and in vitro studies. The mechanisms of protective effects of Oxymatrine are mainly related to its anti-inflammatory, anti-oxidative stress, anti- or pro-apoptotic, anti-fibrotic, metabolism-regulation, and anti-nociceptive functions. In addition, a variety of signal pathways, cells, and molecules are influenced by Oxymatrine, and by these comprehensive actions, maximum therapeutic effects can be achieved. Furthermore, we summarize the protective effects in clinical studies and adverse effects of Oxymatrine. It is believed that through more in-depth animal experiments and standardized clinical research, Oxymatrine holds a bright future in the process of organ and tissue protection and has a significant therapeutic promise to translate from bench to bedside.
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arsenic trioxide induced herg k channel deficiency can be rescued by matrine and Oxymatrine through up regulating transcription factor sp1 expression
Biochemical Pharmacology, 2013Co-Authors: Ying Zhang, Zengxiang Dong, Liyan Jin, Kaiping Zhang, Xin Zhao, Yan Gong, Mingming Sun, Baofeng YangAbstract:The human ether-a-go-go-related gene (hERG) encodes the rapidly activating, delayed rectifier potassium channel (IKr) important for cardiac repolarization. Dysfunction of the hERG channel can cause Long QT Syndrome (LQTS). A wide variety of structurally diverse therapeutic compounds reduce the hERG current by acute direct inhibition of the hERG current or/and selective disruption of hERG protein expression. Arsenic trioxide (As(2)O(3)), which is used to treat acute promyelocytic leukemia, can cause LQTS type 2 (LQT2) by reducing the hERG current through the diversion of hERG trafficking to the cytoplasmic membrane. This cardiotoxicity limits its clinical applications. Our aim was to develop cardioprotective agents to decrease As(2)O(3)-induced cardiotoxicity. We reported that superfusion of hERG-expressing HEK293 (hERG-HEK) cells with matrine (1, 10 μM) increased the hERG current by promoting hERG channel activation. Long-term treatment with 1 μM matrine or Oxymatrine increased expression of the hERG protein and rescued the hERG surface expression disrupted by As(2)O(3). In addition, Matrine and Oxymatrine significantly shortened action potential duration prolonged by As(2)O(3) in guinea pig ventricular myocytes. These results were ascribed to the up-regulation of hERG at both mRNA and protein levels via an increase in the expression of transcription factor Sp1, an established transactivator of the hERG gene. Therefore, matrine and Oxymatrine may have the potential to cure LQT2 as a potassium channel activator by promoting hERG channel activation and increasing hERG channel expression.
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Oxymatrine diminishes the side population and inhibits the expression of β catenin in mcf 7 breast cancer cells
Medical Oncology, 2011Co-Authors: Ying Zhang, Bingkui Piao, Yong Zhang, Baojin Hua, Wei Hou, Xiaoyun Zhu, Yingxia Pei, Hongsheng LinAbstract:Cancer stem cells (CSCs) play a critical role in both cancer initiation and relapse as they are resistant to most cytotoxic agents and able to proliferate indefinitely. The plant alkaloid Oxymatrine has many biological activities including the ability to induce cell cycle arrest and apoptosis, which makes it a potentially useful agent for targeting cancer cells. In order to determine whether it has beneficial pharmacological properties to eradicate CSCs, we analyzed the effects of Oxymatrine on MCF-7 breast cancer cells. Cancer stem-like cells’ (side population, SP) identification and sorting were performed. The inhibitory effect of Oxymatrine was evaluated on the sorted SP and non-SP cells. The results indicated that Oxymatrine caused a dose-dependent reduction in the proliferation of MCF-7 cells and a decrease in SP cells. Wnt/β-catenin signaling pathway was also examined by analyzing the expression of total β-catenin and phosphorylated β-catenin in cytoplasm, and the results showed that the growth inhibitory effects of Oxymatrine treatment on MCF-7 cells may be due to the inhibition of SP and Wnt/β-catenin signaling pathway. Further work is warranted to explore whether Oxymatrine may be a useful novel therapeutic drug for targeting breast CSCs.
Xiuqin Yue - One of the best experts on this subject based on the ideXlab platform.
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protective effects of Oxymatrine against arsenic trioxide induced liver injury
Oncotarget, 2017Co-Authors: Qinghai Liu, Long Fan, Wei Xiao, Lei Zhao, Yu Wang, Fei Lan, Bin Jia, Hua Feng, Changman Zhou, Xiuqin YueAbstract:// Li Li 1 , Qinghai Liu 1 , Long Fan 1 , Wei Xiao 1 , Lei Zhao 1 , Yu Wang 1 , Weiguang Ye 1 , Fei Lan 1 , Bin Jia 1 , Hua Feng 1 , Changman Zhou 2 , Xiuqin Yue 3 , Guogang Xing 4 , Tianlong Wang 1 1 Department of Anesthesiology, Xuanwu Hospital, Capital Medical University, Beijing, China 2 Department of Anatomy & Histology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China 3 Department of Anesthesiology, the First Affiliated Hospital of Xinxiang Medical University, Henan, China 4 Department of Neurobiology, School of Basic Medical Sciences, Peking University, Beijing, China Correspondence to: Guogang Xing, email: li_limzk@163.com Tianlong Wang, email: w_tl5595@hotmail.com Keywords: Oxymatrine, arsenic trioxide, liver, HO-1, Nrf-2 Received: July 25, 2016 Accepted: September 06, 2016 Published: October 5, 2016 ABSTRACT Oxymatrine, a quinolizidine natural drug extracted from Sophora japonica , has been reported to have neuroprotective effect and cardioprotective effect. However, the protective effect of Oxymatrine on arsenic trioxide (As 2 O 3 )-induced liver injury has not been reported. In the present study, we investigated the protective effects of Oxymatrine on As 2 O 3 -induced liver injury in rats. Male Wistar rats were administrated 3mg/kg As 2 O 3 intravenous injection on alternate days for 4 days. Oxymatrine was given 1 h before As 2 O 3 treatment. The results showed that Oxymatrine inhibited As 2 O 3 -induced hepatic pathological damage, liver ROS level and MDA level in a dose-dependent manner. As 2 O 3 decreased the antioxidant enzymes SOD, GPX, and CAT activity and the decrease was inhibited by treatment of Oxymatrine. Furthermore, Oxymatrine attenuated the retention of arsenic in liver tissues and improved the expression of Nrf2 and HO-1. In conclusion, our results suggested that Oxymatrine protected against As 2 O 3 -induced oxidative damage by activating Nrf2/HO-1 signaling pathway.
