Oxymatrine
Oxymatrine has exhibited anti-hepatitis virus infection, anti-hepatic fibrosis, anti-inflammation, anti-anaphylaxis and other immune-regulation, it induces human pancreatic cancer PANC-1 cells apoptosis via regulating expression of Bcl-2 and IAP families, and releasing of cytochrome C. It can attenuate diabetes-associated cognitive deficits in rats, which is associated with oxidative stress, inflammation and apoptotic cascades, it is proven to protect ischemic and reperfusion injury in liver, intestine and heart.
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J Exp Clin Cancer Res. 2011; 30(1): 66.
Oxymatrine induces human pancreatic cancer PANC-1 cells apoptosis via regulating expression of Bcl-2 and IAP families, and releasing of cytochrome c[Pubmed:
21714853]
Oxymatrine, an isolated extract from traditional Chinese herb Sophora Flavescens Ait, has been traditionally used for therapy of anti-hepatitis B virus, anti-inflammation and anti-anaphylaxis. The present study was to investigate the anti-cancer effect of Oxymatrine on human pancreatic cancer PANC-1 cells, and its possible molecular mechanism.
METHODS AND RESULTS:
The effect of Oxymatrine on the viability and apoptosis was examined by methyl thiazolyl tetrazolium and flow cytometry analysis. The expression of Bax, Bcl-2, Bcl-x (L/S), Bid, Bad, HIAP-1, HIAP-2, XIAP, NAIP, Livin and Survivin genes was accessed by RT-PCR. The levels of cytochrome c and caspase 3 protein were assessed by Western blotting.
Oxymatrine inhibited cell viability and induced apoptosis of PANC-1 cells in a time- and dose-dependent manner. This was accompanied by down-regulated expression of Livin and Survivin genes while the Bax/Bcl-2 ratio was upregulated. Furthermore, Oxymatrine treatment led to the release of cytochrome c and activation of caspase-3 proteins.
CONCLUSIONS:
Oxymatrine can induce apoptotic cell death of human pancreatic cancer, which might be attributed to the regulation of Bcl-2 and IAP families, release of mitochondrial cytochrome c and activation of caspase-3.
Med Oncol. 2011 Dec;28 Suppl 1:S99-107.
Oxymatrine diminishes the side population and inhibits the expression of β-catenin in MCF-7 breast cancer cells.[Pubmed:
21069479 ]
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.
METHODS AND RESULTS:
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.
CONCLUSIONS:
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.
Phytother Res . 2016 Jul;30(7):1104-12.
Potential Signaling Pathways Involved in the Clinical Application of Oxymatrine[Pubmed:
27165263]
Abstract
Oxymatrine, an alkaloid component extracted from the roots of Sophora species, has been shown to have antiinflammatory, antifibrosis, and antitumor effects and the ability to protect against myocardial damage, etc. The potential signaling pathways involved in the clinical application of Oxymatrine might include the TGF-β/Smad, toll-like receptor 4/nuclear factor kappa-light-chain-enhancer of activated B cells, toll-like receptor9/TRAF6, Janus kinase/signal transduction and activator of transcription, phosphatidylinositol-3 kinase/Akt, delta-opioid receptor-arrestinl-Bcl-2, CD40, epidermal growth factor receptor, nuclear factor erythroid-2-related factor 2/heme oxygenase-1 signaling pathways, and dimethylarginine dimethylaminohydrolase/asymmetric dimethylarginine metabolism pathway. In this review, we summarize the recent investigations of the signaling pathways related to Oxymatrine to provide clues and references for further studies on its clinical application. Copyright © 2016 John Wiley & Sons, Ltd.
Keywords: clinical application; Oxymatrine; signaling pathway.
Brain Res. 2009 May 1;1268:174-80.
Oxymatrine protects rat brains against permanent focal ischemia and downregulates NF-kappaB expression.[Pubmed:
19285049 ]
METHODS AND RESULTS:
Male, Sprague-Dawley rats were randomly assigned to four groups: permanent middle cerebral artery occlusion (pMCAO), high dose (pMCAO+Oxymatrine 120 mg/kg), low dose (pMCAO+Oxymatrine 60 mg/kg) and sham operated group. We used a permanent middle cerebral artery occlusion model and administered Oxymatrine intraperitoneally immediately after cerebral ischemia and once daily on the following days. At 24 h after MCAO, neurological deficit was evaluated using a modified six point scale; brain water content was measured; NF-kappaB expression was measured by immunohistochemistry, Western blotting and RT-PCR. Infarct volume was analyzed with 2, 3, 5-triphenyltetrazolium chloride (TTC) staining at 72 h.
Compared with pMCAO group, neurological deficit in high dose group was improved (P<0.05), infarct volume was decreased (P<0.001) and cerebral edema was alleviated (P<0.05). Consistent with these indices, immunohistochemistry, Western blot and RT-PCR analysis indicated that NF-kappaB expression was significantly decreased in high dose group. Low dose of Oxymatrine did not affect NF-kappaB expression in pMCAO rats.
CONCLUSIONS:
Oxymatrine reduced infarct volume induced by pMCAO, this effect may be through the decreasing of NF-kappaB expression.
Chinese Journal of Digestion, 2003, 11(31):4912-5.
Study on the anti-inflammatory mechanism of oxymatrine in dextran sulfate sodium induced colitis of rats[Reference:
WebLink]
METHODS AND RESULTS:
To investigate the anti inflammatory mechanism of Oxymatrine(OM)in dextran sulfate sodium(DSS) induced colitis of rats. Results Compared with DSS control group, the inflammatory symptoms and histological damages of colonic mucosa in OM treated group were significantly improved( P 0.02, P 0.05), the serum levels of TNF α, IL 6 and the expression of NF κB, ICAM 1 in colonic mucosa were significantly reduced( P 0.01, P 0.05, P 0.05, P 0.01).
CONCLUSIONS:
The fact that OM can reduce the serum level of TNF α, IL 6 and the expression of NF κB and ICAM 1 in colonic mucosa in DSS induced colitis of rats indicates that OM may ameliorates the colonic inflammation and thus alleriate diarrhea and bloody stool.
Acta Pharmacol. Sin., 2014, 35(3):331-8.
Oxymatrine attenuates diabetes-associated cognitive deficits in rats.[Pubmed:
24442148]
Oxymatrine (OMT) is the major quinolizidine alkaloid extracted from the root of Sophora flavescens Ait (the Chinese herb Kushen) and exhibits diverse pharmacological actions.
METHODS AND RESULTS:
In this work we investigated the effects of OMT on diabetes-associated cognitive decline (DACD) in a rat model of diabetes and explored the mechanisms of action. The diabetic rats exhibited markedly reduced body weight and increased plasma glucose level. The memory function of the rats assessed using Morris water maze test showed significant reduction in the percentage of time spent in the target quadrant and the number of times crossing the platform, coupled with markedly prolongation of escape latency and mean path length. Moreover, the rats showed oxidative stress (significantly increased MDA, decreased SOD and reduced GSH levels), as well as significant increases of NF-κB p65 unit, TNF-α, IL-1β and caspase-3 levels in the cerebral cortex and hippocampus. Chronic treatment with OMT dose-dependently reversed these behavioral, biochemical and molecular changes in the diabetic rats. However, the swimming speed had no significant difference among the control, diabetic and OMT-treated diabetic rats.
CONCLUSIONS:
Chronic treatment with OMT alleviates diabetes-associated cognitive decline in rats, which is associated with oxidative stress, inflammation and apoptotic cascades.
Int J Biol Macromol. 2010 May 1;46(4):425-8.
Astragalus polysaccharide and oxymatrine can synergistically improve the immune efficacy of Newcastle disease vaccine in chicken.[Pubmed:
20149818]
METHODS AND RESULTS:
Three hundred and sixty 14-day-old chickens were divided into seven groups. The chickens, except for blank control group, were vaccinated with Newcastle disease vaccine, repeated at 28 days old. At the same time of the first vaccination, the chickens in three astragalus polysaccharide-Oxymatrine (AP-OM) groups were orally administrated respectively with the mixture of AP-OM at high, medium and low concentrations, in astragalus polysaccharide (AP) group and Oxymatrine (OM) group, with corresponding medicine, in non-medicine (NM) control group, with equal volume of physiological saline, once a day for 3 successive days. On 14, 21, 28, 35 and 42 days after the first vaccination, the changes of peripheral lymphocyte proliferation and serum antibody titers of the chickens were determined by MTT method and hemagglutination inhibition test. On 14, 28 and 42 days after the first vaccination, the serum IL-2 concentration was determined by Enzyme-linked Immunosorbent Assay (ELISA). The results showed that at most time points, the lymphocyte proliferation, antibody titers and IL-2 concentrations of 5 medicine-administrating groups were significantly higher than that of corresponding NM group. At some time points, the lymphocyte proliferation, antibody titers and IL-2 concentrations in high and medium doses of AP-OM groups were significantly or numberly higher than those in AP group and OM group.
CONCLUSIONS:
It indicated that AP-OM could significantly improve the immune efficacy of Newcastle disease vaccine, astragalus polysaccharide and Oxymatrine possessed synergistical immunoenhancement.
J Ethnopharmacol. 2005 Apr 8;98(1-2):177-83.
Attenuation of acute lung injury in mice by oxymatrine is associated with inhibition of phosphorylated p38 mitogen-activated protein kinase.[Pubmed:
15763380 ]
Oxymatrine is one of the alkaloids extracted from Chinese herb Sophora japonica (Sophora flavescens Ait.) with activities of anti-inflammation, inhibiting immune reaction, antivirus, protecting hepatocytes and antihepatic fibrosis. However, the effect of Oxymatrine on acute lung injury (ALI) has not been known yet.
METHODS AND RESULTS:
In this study, the effect of Oxymatrine on ALI was investigated using an oleic acid-induced ALI mouse model. Morphological findings showed that the oleic acid group demonstrated a marked lung injury represented by prominent atelectasis, intraalveolar and interstitial patchy hemorrhage, edema, thickened alveolar septum, formation of hyaline membranes and the existence of inflammatory cells in alveolar spaces. While in the Oxymatrine/dexamethasone group, these changes were less severe and in the vicinity of the control group. Furthermore, pretreatment with Oxymatrine significantly alleviated oleic acid-induced lung injury accompanied by reduction of lung index and wet-to-dry weight ratio, decreases in serum TNF-alpha level and inhibition of phosphorylated p38 MAPK.
CONCLUSIONS:
These findings suggest that Oxymatrine has a beneficial effect on acute lung injury induced by oleic acid in mice and may inhibit the production of proinflammatory cytokine, TNF-alpha, by means of the inhibition of p38 MAPK.
World J Gastroenterol. 2001 Feb;7(1):49-52.
Inhibition of hepatitis B virus by oxymatrine in vivo.[Pubmed:
11819732 ]
To investigate the anti-HBV effect of Oxymatrine (oxy) in vivo.
METHODS AND RESULTS:
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.
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 days. 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 100mg/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, 200mg/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.
CONCLUSIONS:
Oxymatrine can reduce the contents of HBsAg and HBcAg in transgenic mice liver,longer treatment time and larger dosage do not yield better effects.