Oxymatrine

264.36

264.36

1312995-182-4

White to off-white powder|White dice from crystal

29399990

38.4

log Kow = 0.95 (est)

white to off-white

199-201 °C

957.1°C at 760 mmHg

1.637

methanol: soluble10mg/mL, clear, colorless

2-8°C

8.75X10-11 mm Hg at 25 °C (est)

Peritoneal-mouse LD50: 521 mg/kg; intravenous-mouse LD50: 150 mg/kg

Combustible; Fire breaks down toxic nitrogen oxide fumes

Slight amber aroma

Henry's Law constant = 1.04X10-18 atm-cu m/mol at 25 °C (est)

Hydroxyl radical reaction rate constant = 91.0350X10-12 cu cm/molecule-sec at 25 °C (est)

NONH for all modes of transport

3

22-20/22

24/25

OQ1770000

Xn

Warehouse low temperature, ventilated, dry

H302

SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.|SRP: Wastewater from contaminant suppression, cleaning of protective clothing/equipment, or contaminated sites should be contained and evaluated for subject chemical or decomposition product concentrations. Concentrations shall be lower than applicable environmental discharge or disposal criteria. Alternatively, pretreatment and/or discharge to a permitted wastewater treatment facility is acceptable only after review by the governing authority and assurance that "pass through" violations will not occur. Due consideration shall be given to remediation worker exposure (inhalation, dermal and ingestion) as well as fate during treatment, transfer and disposal. If it is not practicable to manage the chemical in this fashion, it must be evaluated in accordance with EPA 40 CFR Part 261, specifically Subpart B, in order to determine the appropriate local, state and federal requirements for disposal.|All waste must be handled in accordance with local, state and federal regulations.: Recycle wherever possible. Consult manufacturer for recycling options or consult Waste Management Authority for disposal if no suitable treatment or disposal facility can be identified. Dispose of by: Burial in a licensed land-fill or Incineration in a licensed apparatus (after admixture with suitable combustible material) Decontaminate empty containers. Observe all label safeguards until containers are cleaned and destroyed.

Avoid contamination with oxidizing agents i.e. nitrates, oxidizing acids,chlorine bleaches, pool chlorine etc. as ignition may result.

|Warning|H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]|P264, P270, P301+P312, P330, and P501|Aggregated GHS information provided by 196 companies from 1 notifications to the ECHA C&L Inventory.

Glasses: Chemical goggles; Gloves; Respirator: Particulate.|Safety glasses with side shields Chemical goggles. Contact lenses pose a special hazard; soft lenses may absorb irritants and all lenses concentrate them.|Select gloves tested to a relevant standard (e.g. Europe EN 374, US F739). When prolonged or frequently repeated contact may occur, a glove with a protection class of 5 or higher (breakthrough time greater than 240 minutes according to EN 374) is recommended. When only brief contact is expected, a glove with a protection class of 3 or higher (breakthrough time greater than 60 minutes according to EN 374) is recommended. Contaminated gloves should be replaced.|Use appropriate NIOSH-certified respirator based on informed professional judgement. In conditions where no reasonable estimate of exposure can be made, assume the exposure is in a concentration IDLH and use NIOSH-certified full face pressure demand SCBA with a minimum service life of 30 minutes, or a combination full facepiece pressure demand SAR with auxiliary self-contained air supply. Respirators provided only for escape from IDLH atmospheres shall be NIOSH-certified for escape from the atmosphere in which they will be used.

Extinguishing Media: Water spray or fog, foam, dry chemical powder, BCF (where regulations permit), carbon dioxide.|Alert Emergency Responders and tell them location and nature of hazard. Wear breathing apparatus plus protective gloves. Prevent, by any means available, spillage from entering drains or water course. Use water delivered as a fine spray to control fire and cool adjacent area. DO NOT approach containers suspected to be hot. Cool fire exposed containers with water spray from a protected location. If safe to do so, remove containers from path of fire. Equipment should be thoroughly decontaminated after use.

SRP: Contaminated protective clothing should be segregated in such a manner so that there is no direct personal contact by personnel who handle, dispose, or clean the clothing. The completeness of the cleaning procedures should be considered before the decontaminated protective clothing is returned for reuse by the workers. Contaminated clothing should not be taken home at the end of shift, but should remain at employee's place of work for cleaning.|SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.|Avoid all personal contact, including inhalation. Wear protective clothing when risk of exposure occurs. Use in a well-ventilated area. Prevent concentration in hollows and sumps. DO NOT enter confined spaces until atmosphere has been checked.|Do not allow material to contact humans, exposed food or food utensils. ... When handling, DO NOT eat, drink or smoke. ... Always wash hands with soap and water after handling.|For more Preventive Measures (Complete) data for Oxymatrine (9 total), please visit the HSDB record page.

moderately toxic

The combination of Radix Angelicae sinensis (Oliv.) Diels and Radix Sophora flavescens Ait. was extensively used in traditional Chinese medicine to treat inflammatory diseases, such as acne, heart disease, and hepatitis. Sodium ferulate (SF) and oxymatrine (OMT) were effective component of Radix Angelicae sinensis (Oliv.) Diels and Radix Sophora flavescens Ait., respectively. In this study, /the authors/ investigated the synergistic anti-inflammatory effect of the combination of SF and OMT, and its modulation on inflammation-associated mediators in RAW 264.7 cells. In vivo, the anti-inflammatory effects of the combination of SF and OMT were evaluated with the xylene-induced mouse ear edema model and the carrageenan-induced rat paw edema model. In vitro, chemokines and cytokines mRNA expressions in lipopolysaccharide (LPS)-activated RAW 264.7 cells were determined by real-time PCR (RT-PCR) microarray analysis. The levels of interleukin-11 (IL-11), C-reactive protein (CRP) and interferon-gamma (INF-gamma) in the supernatant of LPS-stimulated RAW 264.7 cells were measured by enzyme-linked immune-sorbent assay (ELISA). The combination of SF and OMT could significantly inhibit the edema in the xylene-induced mouse ear edema and carrageenan-induced rat paw edema, but no effect was found when each drug was used alone according to above doses. The combination exhibited a better effect in down-regulating mRNA expressions of inflammation-associated mediators in LPS-stimulated RAW 264.7 cells than SF or OMT alone. The ELISA results showed that the combination synergistically inhibited LPS-induced IL-11, CRP and INF-gamma production in a dose-dependent manner. The combination of SF and OMT showed synergistic anti-inflammatory effect, and the activity was probably related to its modulation on inflammation-associated mediators, especially IL-11, CRP and INF-gamma.|Sodium ferulate (SF) and Oxymatrine (OMT) were compounds extracted from Chinese herbs, and have been used in clinical treatment of heart and hepatic diseases, respectively, in China for many years. The objective of this study was to examine the analgesic effect and the mechanism of the combined treatment of SF and OMT. Using the animal pain models by applying Acetic Acid Writhing Test and Formalin Test, the combination of SF and OMT showed significant analgesic effect in dose-dependent manner. In vitro, the combined treatment inhibited the increase in intracellular calcium concentration evoked by capsaicin in the dorsal root ganglion neurons. Importantly, a synergistic inhibitory effect of SF and OMT on the capsaicin-induced currents was demonstrated by whole-cell patch-clamp. Our results suggest that SF and OMT cause significant analgesic effect which may be related to the synergistic inhibition of transient receptor potential vanilloid-1.|/The aim of this was/ to study the effect of oxymatrine-baicalin combination (OB) against HBV replication in 2.2.15 cells and alpha smooth muscle actin (alpha SMA) expression, type I, collagen synthesis in HSC-T6 cells. The 2.2.15 cells and HSC-T6 cells were cultured and treated respectively. HBsAg and HBeAg in the culture supernatants were detected by ELISA and HBV DNA levels were determined by fluorescence quantitative PCR. Total RNA was extracted from HSC-T6 cells and reverse transcribed into cDNA. The cDNAs were amplified by PCR and the quantities were expressed in proportion to beta actin. The total cellular proteins extracted from HSC-T6 cells were separated by electrophoresis. Resolved proteins were electrophoretically transferred to nitrocellulose membrane. Protein bands were revealed and the quantities were corrected by beta actin. In the 2.2.15 cell culture system, the inhibitory rate against secretion of HBsAg and HBeAg in the OB group was significantly stronger than that in the oxymatrine group (HBsAg, P = 0.043; HBeAg, P = 0.026; respectively); HBV DNA level in the OB group was significantly lower than that in the oxymatrine group (P = 0.041). In HSC-T6 cells the mRNA and protein expression levels of alpha SMA in the OB group were significantly lower as compared with those in the oxymatrine group (mRNA, P = 0.013; protein, P = 0.042; respectively); The mRNA and protein expression levels of type I collagen in the OB group were significantly lower as compared with those in the oxymatrine group (mRNA, P < 0.01; protein, P < 0.01; respectively). /The authors concluded that/ OB combination has a better effect against HBV replication in 2.2.15 cells and is more effective against alpha SMA expression and type I collagen synthesis in HSC-T6 cells than oxymatrine in vitro.|Oxymatrine is proven to protect ischemic and reperfusion injury in liver, intestine and heart, this effect is via anti-inflammation and anti-apoptosis. Whether this protective effect applies to ischemic injury in brain, /the authors/ therefore investigate the potential neuroprotective role of oxymatrine and the underlying mechanisms. 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. /The authors/ 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 hr 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 hr. 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. Oxymatrine reduced infarct volume induced by pMCAO, this effect may be through the decreasing of NF-kappaB expression.

/OTHER TERRESTRIAL SPECIES/ Under laboratory conditions, the comparative effects of two insect growth regulators, chlorfluazuron and oxymatrine, and spinosad as a biopesticide were examined on honey bee workers (Apis mellifera L.). Separate groups of bees were left for 24 hr to feed on 50% sucrose solution containing different concentrations of the tested insecticides, and the lethal concentration that caused 50% mortality (LC50) was estimated. The inhibitory effects on acetylcholinesterase (AChE) and adenosine triphosphatase (ATPase) activities as biochemical indicators were determined in vivo after 24 hr in head, thorax, and abdomen of surviving bees obtained after treatments with a view to explore the possible mode of action of these compounds. Results indicated that exposure to spinosad showed toxicity to honey bees with LC50 value of 7.34 mg/L, followed by oxymatrine (LC50 = 10.68 mg/L), while chlorfluazuron was the least acutely toxic of the tested compounds (LC50 = 2,526 mg/L). Oxymatrine and spinosad at the same tested concentrations (2.5, 5, 10, and 20 mg/L) significantly inhibited AChE activity in different organs of honey bee workers, and high inhibition percentage was obtained with the enzyme isolated from the thorax... addition, the toxic effects of the tested compounds on activity of ATPase indicated that spinosad caused the highest inhibitory effect in different organs compared with oxymatrine at the same concentrations, and high inhibition was found with ATPase isolated from the head. The results also indicated that oxymatrine was the least active compound for inhibition of AChE and ATPase.

Oxymatrine is found in the species Sophora flavescens, S. macrocarpa, Ammothamnus lehmannii, E. horsfeldii, and other plants (Leguminosae)(1).

Oxymatrine's production and use as a biological agent in traditional medicines(1) may result in its release to the environment through various waste streams(SRC).

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 2000(SRC), determined from a structure estimation method(2), indicates that oxymatrine is expected to have low mobility in soil(SRC). Volatilization of oxymatrine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 1.0X10-18 atm-cu m/mole(SRC), using a fragment constant estimation method(3). Oxymatrine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.7X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(3). Biodegradation data in soil were not available(SRC, 2012).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 2000(SRC), determined from a structure estimation method(2), indicates that oxymatrine is expected to adsorb to suspended solids and sediment(SRC). Volatilization from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 1.0X10-18 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). According to a classification scheme(5), an estimated BCF of 3(SRC), from an estimated log Kow of 0.95(6) and a regression-derived equation(2), suggests the potential for bioconcentration in aquatic organisms is low(SRC). Biodegradation data in water were not available(SRC, 2012).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), oxymatrine, which has an estimated vapor pressure of 8.7X10-11 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase oxymatrine may be removed from the air by wet and dry deposition(SRC). Oxymatrine contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

The rate constant for the vapor-phase reaction of oxymatrine with photochemically-produced hydroxyl radicals has been estimated as 9.10X10-11 cu cm/molecule-sec at 25 °C(SRC) using a structure estimation method(1). This corresponds to an atmospheric half-life of about 1.41 hours at an atmospheric concentration of 5X10+5 hydroxyl radicals per cu cm(1). Hydrolysis is not expected to be an important environmental fate process due to the lack of functional groups that hydrolyze under environmental conditions(2). Oxymatrine contains chromophores that absorb at wavelengths >290 nm(2) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for oxymatrine(SRC), using an estimated log Kow of 0.95(1) and a regression-derived equation(2). According to a classification scheme(3), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of oxymatrine can be estimated to be 2000(SRC). According to a classification scheme(2), this estimated Koc value suggests that oxymatrine is expected to have low mobility in soil.

The Henry's Law constant for oxymatrine is estimated as 1.0X10-18 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that oxymatrine is expected to be essentially nonvolatile from water surfaces(2). Oxymatrine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 8.7X10-11 mm Hg(3)(SRC), determined from a fragment constant method(3).

Occupational exposure to oxymatrine may occur through inhalation and dermal contact with this compound at workplaces where oxymatrine is produced or used. Exposure to oxymatrine among the general population may be limited to those administered drugs containing oxymatrine. (SRC)

Anti-Arrhythmia Agents; Antiviral Agents|The aim of this study was/ to evaluate the efficacy and safety of capsule oxymatrine in the treatment of chronic hepatitis B. A randomized 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 weeks, 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. 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. /It was concluded that/ oxymatrine is an effective and safe agent for the treatment of chronic hepatitis B.

Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade. (See all compounds classified as Anti-Arrhythmia Agents.)|Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly. (See all compounds classified as Antiviral Agents.)

The aim of this study was to investigate the preventive effects of OM on bleomycin (BLM)-induced pulmonary fibrosis (PF) and to further explore the underlying mechanisms. C57BL/6 mice were randomly assigned to five groups: the saline sham group; the BLM group, in which mice were endotracheally instilled with BLM (3.0 mg/kg); and the BLM plus OM groups, in which OM was given to mice daily (10, 20 or 40 mg/kg) one day after BLM instillation for 21 days. The bronchoalveolar lavage fluid (BALF) and lung tissues were collected at 15 and 22 days post BLM administration, respectively. Lung tissues were stained with hematoxylin and eosin (H&E) for histological evaluation. Levels of tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6) and nitric oxide (NO) in mouse BALF were measured, as well as myeloperoxidase (MPO) activity and malondialdehyde (MDA) content in lung homogenates. The inducible nitric oxide synthase (iNOS) expression in the lung tissues was determined by immunohistochemical staining, quantitative real-time PCR and western blot analysis. Moreover, the expression of transforming growth factor (TGF)-beta1, Smad2, Smad3, p-Smad2 and p-Smad3 were also detected. /Investigators/ found that OM improved BLM-induced lung pathological changes, inhibited MPO activity and reduced MDA levels in a dose-dependent manner. OM also dose-dependently inhibited the release of TNF-alpha and IL-6, and decreased the expression of iNOS in lung tissues and thus prevented NO release in response to BLM challenge. In addition, OM decreased the expression of TGF-beta1, p-Smad2 and p-Smad3, which are all important members of the TGF-beta/Smad signaling pathway. /This/ study provides evidence that OM significantly ameliorated BLM-induced PF in mice via the inhibition of iNOS expression and the TGF-beta/Smad pathway.|/The authors/ focus on the mechanisms of pharmacologic action in /oxymatrine/ (OMT) by detecting its pharmacological properties against focal cerebral ischemia in vivo and NMDA-induced neurotoxicity in vitro. OMT prevented cerebral ischemic injury in mice induced via a 2hr middle cerebral artery occlusion and a 24h reperfusion, in vivo. In vitro cultured neurons challenged with N-methyl-d-aspartate (NMDA, 200uM) for 30min showed significant decrease in the viability of neurons; however, OMT was able to protect neurons against induced neurotoxicity via NMDA exposure. Western blot analysis revealed that OMT decreased the expression of Bax and repaired the balance of pro- and anti-apoptotic proteins. Furthermore, OMT significantly reversed the up-regulation of NR2B and inhibited the calcium overload in the cultured neurons after challenging the NMDA. OMT showed partial protection in the cortical neurons via down-regulation of NR2B containing NMDA receptors and up-regulation of Bcl-2 family...|Oxymatrine, extracted from a traditional Chinese herb, Sophora flavescens Ait, has shown a variety of pharmacological actions. /The authors/ have proved that oxymatrine protected brain from ischemic damage. However, little is known about the exact mechanisms of this effect. This study is to investigate the potential neuroprotection of oxymatrine and explore the underlying mechanisms. Male Sprague-Dawley rats were subjected to acute permanent middle cerebral artery occlusion (MCAO). Oxymatrine was administered immediately after cerebral ischemia. At 24 hours after MCAO, brain water content and infarct volume were measured. The expression of 12/15-lipoxygenase (12/15-LOX), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylated p38 MAPK (phospho-p38 MAPK), and cytosolic phospholipase A2 (cPLA2) was measured by immunohistochemistry, western blot and reverse transcription-polymerase chain reaction (RT-PCR). Compared with MCAO group, oxymatrine dramatically reduced brain water content (P<0.05) and infarct volume (P<0.05). Consistent with these indices, the overexpressions of 12/15-LOX, phospho-p38 MAPK, and cPLA2 were significantly decreased in oxymatrine group. But the expression of p38 MAPK was not affected at the mRNA level. Oxymatrine protected the brain from damage caused by MCAO; this effect may be through down-regulation of 12/15-LOX, phospho-p38 MAPK, and cPLA2, but not through down-regulation of p38 MAPK.|Oxymatrine, a natural quinolizidine alkaloid, has been known having cytotoxic and chemopreventive effects on various cancer cells. To investigate the possible mechanism of oxymatrine's role on cancer cells, in the present study, /the authors/ examined further the effects of oxymatrine on the growth, proliferation, apoptosis and expression of bcl-2 and p53 gene in human hepatoma SMMC-7721 cells in vitro. /The/ results show that oxymatrine notably inhibits the growth and proliferation of SMMC-7721 cells and it present a dose-dependence and time-dependence manner within definite reacting dose and time. Oxymatrine block SMMC-7721 cells in G2/M and S phase; prevent cells entering into G0/G1 phase. It results in an obvious accumulation of G2/M and S phase cells while decrease of G0/G1 phase cells. Oxymatrine induce apoptosis of SMMC-7721 cells and apoptotic rate amount to about 60% after treatment with 1.0 mg/mL oxymatrine for 48 hr. /The authors/ also find that oxymatrine down-regulate expression of bcl-2 gene while up-regulate expression of p53 gene. These results demonstrate that oxymatrine inhibit the proliferation and induce apoptosis of human hepatoma SMMC-7721 cells, and suggest that this effect was mediated probably by a significant cell cycle blockage in G2/M and S phase, down-regulation of bcl-2 and up-regulation of p53.|...The objective of the study was to investigate the effects of matrine or oxymatrine on hepatic cytochrome P450 (CYP450) and the underlying molecular mechanisms. Matrine (15, 75 and 150 mg/kg) or oxymatrine (36, 180 and 360 mg/kg) was administered to rats for 14 days and the activities of CYP450 were measured by the quantification of the metabolites from multiple CYP450 probe substrates, using validated liquid chromatography coupled with liquid chromatography-tandem mass spectrometry detection (LC-MS/MS) and high-performance liquid chromatography methods. The mRNA and protein expression levels of CYPs were determined by quantitative real-time reverse-transcription polymerase chain reaction and Western blotting analysis respectively. Interactions between matrine or oxymatrine and human constitutive androstane (CAR), pregnane X receptor were evaluated by means of the reporter gene assay in CV-1 cells. /This/ study showed that matrine and oxymatrine significantly induced the activity and gene expression of CYP2B1 in a dose-dependent manner; matrine (150 mg/kg) slightly induced the mRNA and protein expression of CYP2E1 and mildly inhibited the mRNA and protein expression of CYP3A1 in rats. Matrine or oxymatrine could activate human CAR and induce the CYP2B reporter construct in CV-1 cells. These results reveal that matrine and oxymatrine can induce the activity and expression of CYP2B1/2 in rats, and the underlying mechanism may be related to the activation of CAR.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/HUMAN EXPOSURE STUDIES/ /The aim of this study was/ to evaluate the efficacy and safety of oxymatrine capsule in treatment of hepatic fibrosis in patients with chronic viral hepatitis. 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. 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. Oxymatrine capsule is effective and safe in treatment of hepatic fibrosis due to chronic viral hepatitis.|/ALTERNATIVE and IN VITRO TESTS/ /The aim of this study was/ to investigate the synergistic effect of oxymatrine (OM) and angiogenesis inhibitor NM-3 on modulating apoptosis in human gastric cancer cell lines SGC-7901, MKN-45, MKN-74. Human gastric cancer lines SGC-7901, MKN-45, MKN-74 were treated with OM in the absence and presence of NM-3. The inhibitory rates were detected by MTT assay. Synergistic effect of OM and NM-3 on the growth of survivin, bcl-2, bax and p53 in SGC-7901 cells were examined by semiquantitative RT-PCR and Western blotting, and their growth inhibitory effects were also observed on SGC-7901 tumor xenograft in nude mice. OM combined with NM-3 exhibited a synergistic inhibitory effect on the growth of SGC-7901, MKN-45 and MKN-74 cells in a time-dependent manner. Twenty-four hours after treatment with OM, NM-3 alone and their combination, mRNA expression of survivin and bcl-2 in SGC-7901 cells decreased, p53 mRNA expression increased. OM (4 g/L) combined with NM-3 significantly increased the expression of p53 mRNA and decreased the expression of survivin and bcl-2 compared with either agent alone (193% +/- 34% vs 129% +/- 12%; 44% +/- 18% vs 92% +/- 18%; 36 +/- 17% vs 93% +/- 23%, P < 0.05). Western blotting showed that the synergistic effect of OM and NM-3 on protein translation of survivin, bcl-2 and p53 was in accordance with their mRNAs. Furthermore, OM/NM-3 combination obviously exhibited antitumor growth effect in xenografted human gastric cancer cells SGC-7901 compared with either agent alone. OM combined with NM-3 has synergistic inhibitory effects on human gastric cancer cells in vitro and can suppress the growth of xenografted human gastric cancer cells SGC-7901 in vivo.|/ALTERNATIVE and IN VITRO TESTS/ The effects of oxymatrine on the proliferation of human tonsillar cells and mouse splenocytes were observed. Results indicated that oxymatrine can increase the proliferation of human tonsillar cells and mouse splenocytes.|/OTHER TOXICITY INFORMATION/ The aim of this study was to prepare oxymatrine (OMT) mixed micellar nanoparticles to delay release of the drug and enhance its cytotoxicity against cancer cells. A co-solvent evaporation method using lipoid E80, lipoid S75, MPEG-PLA and Poloxamer 188 was chosen to prepare the OMT formulation, and its release characteristics, cytotoxic activity in vitro and physical characteristics were evaluated. The results showed that OMT mixed micellar nanoparticles have sustained release and cytotoxic activity in vitro to the SMMC-7721 cell line.

oxymatrine

Oxymatrine (OMT), a water-soluble drug, has a very low oral bioavailability because of its low membrane permeability and its biotransformation in the gastrointestinal tract. Formulated as an oxymatrine-phospholipid complex (OMT-PLC) can improve the lipid solubility and effectiveness of OMT. The purpose of this study was to explore the utility of the combination of a microemulsion and an OMT-PLC as a topical delivery vehicle for enhancing the absorption and efficacy of OMT. The solubility of OMT-PLC was determined and phase diagrams of microemulsions were constructed. Various microemulsion formulations were developed and characterized by their physicochemical properties, and their in vitro and in vivo permeability through skin. An optimal microemulsion (ME4), which presented as spherical droplets and consisted of 10.0% OMT-PLC, 8.0% isopropyl myristate, 30.0% Cremophor RH40/polyethylene glycol 400 (1:1) and 52.0% water, was selected. It possessed an average droplet size of 32.4 nm, a low viscosity of 113.7 mPa.s, and a high cloud point of 88 degrees C. Compared to the control solution, ME4 provided better skin permeability in vitro and a higher retention ratio of OMT in skin in vivo. Moreover, ME4 significantly enhanced the antiproliferative activity of OMT on scar fibroblasts. These results indicate that the combination of a microemulsion and a phospholipid complex represents an effective vehicle for topical delivery of OMT.