Coptisine

320.32

320.092

0GCL71VN14

DTXSID10188404

40.8

2.5 (est)

212-217 °C

In water, 5.283 mg/L at 25 deg C (est)

Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature -20 deg C. Air, light, and moisture sensitive. Handle and store under inert gas. Storage class (TRGS 510): Non Combustible Solids. /Coptisine chloride/

1.12X10-9 mm Hg at 25 deg C (est)

Henry's Law constant = 7.41X10-19 atm-cu m/mol at 25 °C (est)

Yellowish needles from alcohol. MP 218 °C. Very sparingly soluble in water; sparingly soluble in alcohol; soluble in alkalies /Coptisine hydroxide/|Orange prisms; not melted at 300 °C /Coptisine chloride/|Yellow needles; decomposes above 280 °C /Coptisine iodide/|Yellow crystals; insoluble in water and alcohol (enables separation from berberine and worenine) /Coptisine sulfate/|Hydroxyl radical reaction rate constant = 1.46X10-10 cu cm/molecule-sec at 25 °C (est)

Stable under recommended storage conditions. /Coptisine chloride/

SRP: Recycle any unused portion of the material for its approved use or return it to the manufacturer or supplier. Ultimate disposal of the chemical must consider: the material's impact on air quality; potential migration in air, soil or water; effects on animal, aquatic and plant life; and conformance with environmental and public health regulations. If it is possible or reasonable use an alternative chemical product with less inherent propensity for occupational harm/injury/toxicity or environmental contamination.|Product: Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product. /Coptisine chloride/

Incompatible materials: Strong oxidizing agents. /Coptisine chloride/

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU). /Coptisine chloride/|Skin protection: Handle with gloves. /Coptisine chloride/|Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place. The type of protective equipment must be selected according to the concentration and amount of the dangerous substance at the specific workplace. /Coptisine chloride/|Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU). /Coptisine chloride/

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical, or carbon dioxide. /Coptisine chloride/|Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary. /Coptisine chloride/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment, and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist, or gas. Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal. /Coptisine chloride/

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment, and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist, or gas. /Coptisine chloride/|Precautions for safe handling: Further processing of solid materials may result in the formation of combustible dusts. The potential for combustible dust formation should be taken into consideration before additional processing occurs. Provide appropriate exhaust ventilation at places where dust is formed. /Coptisine chloride/|Appropriate engineering controls: General industrial hygiene practice. /Coptisine chloride/|Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands. /Coptisine chloride/|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.

IDENTIFICATION AND USE: Coptisine, a cytotoxic alkaloid found in Chinese goldthread, is related to berberine. It is used in biochemical studies and has been tested as experimental therapy. HUMAN EXPOSURE AND TOXICITY: Cytotoxicity evaluation of coptisine was conducted on a panel of human and murine cell lines in comparison with the established antitumor drugs mitoxantrone, doxorubicin (Dx), and cisplatin (CDDP). Coptisine was cytotoxic on LoVo and HT-29 and less potent on L-1210, and it was partially crossresistant on the human tumor colon cell line resistant to Dx, LoVo/Dx, whereas it was not significantly crossresistant on the murine leukemia cell line resistant to CDDP, L-1210/CDDP. Coptisine prevents vascular smooth muscle cell proliferation selectively at lower concentrations compared with various cells or other structurally related alkaloids. Coptisine has potential pharmacological activity for reducing cholesterol, and may reduce cholesterol by regulating mRNA and protein expressions of key genes involved in cholesterol metabolism, such as LDLR, CYP7A1, and HMGCR. ANIMAL STUDIES: Coptisine is a potent reversible inhibitor of type A monoamine oxidase. Coptisine inhibits proliferation of vascular smooth muscle cells. In the sub-chronic toxicity study, no mortality and morbidity were observed which could be related to coptisine treatment. Besides, there was no abnormality in clinical signs, body weights, organ weights, urinalysis, hematological parameters, gross necropsy, and histopathology in any of the animals after the oral administration of coptisine.

LD50 Mice oral 852.12 mg/kg

Coptisine is a constituent present in a number of plant families including Papaveraceae, Ranunculaceae and Berberidaceae(1). It is from the root of Coptis japonica Makino (Ranunculaceae)(1,2) and also C. chinensis Franch(3).

Coptisine's production and use as an anti-inflammatory medication(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 270,000(SRC), determined from a structure estimation method(2), indicates that coptisine is expected to be immobile in soil(SRC). Volatilization of coptisine from moist soil surfaces is not expected to be an important fate process(SRC) given an estimated Henry's Law constant of 7.4X10-19 atm-cu m/mole(SRC), using a fragment constant estimation method(2). Coptisine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-9 Hg at 25 °C(SRC), determined from a fragment constant method(2). Biodegradation data in soil were not available(SRC, 2016).|AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 270,000(SRC), determined from a structure estimation method(2), indicates that coptisine 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 7.4X10-19 atm-cu m/mole(SRC), developed using a fragment constant estimation method(2). Coptisine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(3). According to a classification scheme(4), an estimated BCF of 3(SRC), from an estimated log Kow of 2.5(2) 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, 2016).|ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), coptisine, which has an estimated vapor pressure of 1.1X10-9 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 coptisine may be removed from the air by wet and dry deposition(SRC). Coptisine contains chromophores that absorb at wavelengths >290 nm(3) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

Coptisine is not expected to undergo hydrolysis in the environment due to the lack of functional groups that hydrolyze under environmental conditions(1). Coptisine contains chromophores that absorb at wavelengths >290 nm(1) and, therefore, may be susceptible to direct photolysis by sunlight(SRC).

An estimated BCF of 3 was calculated in fish for coptisine(SRC), using an estimated log Kow of 2.5(1) and a regression-derived equation(1). According to a classification scheme(2), 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 coptisine can be estimated to be 270,000(SRC). According to a classification scheme(2), this estimated Koc value suggests that coptisine is expected to be immobile in soil.

The Henry's Law constant for coptisine is estimated as 7.4X10-19 atm-cu m/mole(SRC) using a fragment constant estimation method(1). This Henry's Law constant indicates that coptisine is expected to be essentially nonvolatile from water and moist soil surfaces(2). Coptisine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 1.1X10-9 mm Hg(SRC), determined from a fragment constant method(1).

Occupational exposure to coptisine may occur through dermal contact with this compound at workplaces where coptisine is extracted or used. Use data indicate that the general population may be exposed to coptisine via its medicinal use. (SRC)

/EXPL THER/ Indoleamine 2,3-dioxygenase (IDO), the first and rate-limiting enzyme in the kynurenine pathway (KP) of tryptophan catabolism, was recently established as one of the potential players involved in the pathogenesis of Alzheimer's disease (AD). Coptisine is a main pharmacological active constituent of the traditional Chinese medicinal prescription Oren-gedoku-to (OGT) which has therapeutic potential for the treatment of AD. Our recent studies have demonstrated that OGT significantly inhibited recombinant human IDO activity, which shed light on the possible mechanism of OGT's action on AD. Here, we characterized the effects of coptisine in an AD mouse model on the basis of its IDO inhibitory ability. Coptisine was found to be an efficient uncompetitive IDO inhibitor with a Ki value of 5.8 uM and an IC50 value of 6.3 uM. In AbetaPP/PS1 transgenic mice, oral administration of coptisine inhibited IDO in the blood and decreased the activation of microglia and astrocytes, consequently prevented neuron loss, reduced amyloid plaque formation, and ameliorated impaired cognition. Neuronal pheochromocytoma (PC12) cells induced with amyloid-beta peptide 1-42 and interferon-gamma showed reduction of cell viability and enhancement of IDO activity, while coptisine treatment increased cell viability based on its reversal effect on the enhanced activity of IDO. In conclusion, our present findings provide further evidence supporting the critical links between IDO, KP, and AD, and demonstrate coptisine, a novel IDO inhibitor, as a potential new class of drugs for AD treatment.|/EXPL THER/ Excessive receptor activator of NF-kappaB ligand (RANKL) signaling causes enhanced osteoclast formation and bone resorption. The downregulation of RANKL expression and its downstream signals may be an effective therapeutic approach to the treatment of bone loss diseases such as osteoporosis. Here, we found that coptisine, one of the isoquinoline alkaloids from Coptidis Rhizoma, exhibited inhibitory effects on osteoclastogenesis in vitro. Although coptisine has been studied for its antipyretic, antiphotooxidative, dampness dispelling, antidote, antinociceptive, and anti-inflammatory activities in vitro and in vivo, its effects on osteoclastogenesis have not been investigated. Therefore, we evaluated the effects of coptisine on osteoblastic cells as well as osteoclast precursors for osteoclastogenesis in vitro. The addition of coptisine to cocultures of mouse bone marrow cells and primary osteoblastic cells with 10(-8) M 1alpha,25(OH)(2)D(3) caused significant inhibition of osteoclast formation in a dose-dependent manner. Reverse transcriptase polymerase chain reaction (RT-PCR) analyses revealed that coptisine inhibited RANKL gene expression and stimulated the osteoprotegerin gene expression induced by 1alpha,25(OH)(2)D(3) in osteoblastic cells. Coptisine strongly inhibited RANKL-induced osteoclast formation when added during the early stage of bone marrow macrophage (BMM) cultures, suggesting that it acts on osteoclast precursors to inhibit RANKL/RANK signaling. Among the RANK signaling pathways, coptisine inhibited NF-kappaB p65 phosphorylations, which are regulated in response to RANKL in BMMs. Coptisine also inhibited the RANKL-induced expression of NFATc1, which is a key transcription factor. In addition, 10 uM coptisine significantly inhibited both the survival of mature osteoclasts and their pit-forming activity in cocultures. Thus, coptisine has potential for the treatment or prevention of several bone diseases characterized by excessive bone destruction.|/EXPL THER/ Because myocardial infarction is a major cause of morbidity and mortality worldwide, protecting the heart from the ischemia is the focus of intense research. Coptisine is an isoquinoline alkaloid extracted form Coptidis Rhizoma. This study aims to elucidate if coptisine is responsible for cardioprotection using myocardial infarction (MI) rat models and investigate its potential mechanism of action. Myocardial infarction was produced in rats with 85 mg/kg isoproterenol administered subcutaneously twice at an interval of 24 hr. The rats were randomized into 7 groups: (I) Normal; (II) ISO; (III) ISO+fasudil; (IV) ISO+isosorbide dinitrate (ISDN), and (V-VII) ISO+coptisine (25, 50, and 100 mg/kg). Cardiac function and markers of cardiac ischemic were assessed after MI. Rats pretreated with coptisine (25, 50, and 100 mg/kg) for 21 days and received subcutaneously injected with ISO (85 mg/kg) on the 20th and 21st day at an interval of 24 hr. The results suggested that coptisine has strong antioxidant activity, and it can maintain cell membrane integrity, ameliorate mitochondrial respiratory dysfunction, reduce myocardial cells apoptosis, inhibit RhoA/ROCK expression induced by high-dose isoproterenol administration. Coptisine provided cardioprotection in a model of myocardial infarction, and therefore should be considered as a novel adjunctive therapy for attenuating myocardial damage.|/EXPL THER/ Uncontrolled cell proliferation and robust angiogenesis play critical roles in osteosarcoma growth and metastasis. In this study we explored novel agents derived from traditional Chinese medicinal herbs that potently inhibit osteosarcoma growth and metastasis. Coptisine, an active component of the herb Coptidis rhizoma, markedly inhibited aggressive osteosarcoma cell proliferation. Coptisine induced cell cycle arrest at the G0/G1 phase through downregulation of CDK4 and cyclin D1 expression and effectively suppressed tumor growth in a xenografted mouse model. Coptisine significantly impeded osteosarcoma cell migration, invasion, and capillary-like network formation by decreasing the expression of VE-cadherin and integrin beta3, and diminishing STAT3 phosphorylation. Coptisine significantly elevated blood erythrocyte and hemoglobin levels while still remaining within the normal range. It also moderately increased white blood cell and platelet counts. These data suggest that coptisine exerts a strong anti-osteosarcoma effect with very low toxicity and is a potential anti-osteosarcoma drug candidate.|/EXPL THER/ Coptis chinensis has been used for the treatment of inflammatory diseases in China and other Asian countries for centuries. However, the chemical constituents and mechanism underlying the anti-inflammatory activity of this medicinal plant are poorly understood. Here, coptisine, the main constituent of C. chinensis, was shown to potently inhibit the production of nitric oxide (NO) by suppressing the protein and mRNA expressions of inducible nitric oxide synthase (iNOS) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Coptisine also inhibited the production of the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) by suppressing expression of cytokine mRNA. Coptisine suppressed the degradation of inhibitor of nuclear factor kappaBalpha (IkappaBalpha) and phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and phosphoinositide 3-kinase/Akt (PI3K/Akt). Coptisine had no effect on the expression of toll-like receptor 4 (TLR-4) and myeloid differentiation factor 88 (MyD88) as well as LPS binding to TLR-4. Coptisine also inhibited carrageenan-elicited rat paw edema and reduced the release of TNF-alpha and NO in rat inflamed tissue. These results suggest that coptisine inhibits LPS-stimulated inflammation by blocking nuclear factor-kappa B, MAPK, and PI3K/Akt activation in macrophages, and can be used as an agent for the prevention and treatment of inflammatory diseases.

Corydalis saxicola Bunting (Yanhuanglian) is an important component in various prescriptions in traditional Chinese medicine. Yanhuanglian has been demonstrated to possess many pharmacological activities, including antibacterial, antiviral, and anticancer activities. The active fractions are dehydrocavidine, coptisine, dehydroapocavidine, and tetradehydroscoulerine. The purpose of the present study was to examine in vivo pharmacokinetics and tissue distribution in rats by using high-performance liquid chromatography (HPLC) coupled with tandem mass spectrometry. Systemic clearance of the four active alkaloids in plasma was over 93% of hepatic blood flow, indicating they may be quickly eliminated via hepatic clearance. Less than 10% drugs was excreted via urine following intravenous and oral administration, suggesting that these four alkaloids may undergo significant metabolism in the body or the drug may be excreted via other routes other than urine. There was significantly lower excretion of these four alkaloids following oral than intravenous administration, suggesting a significant first pass effect after oral administration. There appeared to be wide distribution of those four alkaloids in rats as demonstrated by the higher apparent volume of distribution. Our results have also demonstrated that the four alkaloids can be absorbed following oral administration although there were less than 15% of drugs absorbed into systemic circulation. In summary, the favorable oral bioavailability properties of those four active alkaloids in rats make Yanhuanglian extract worth further investigation for improving oral bioavailability.|To study the absorption of coptisine chloride (COP) and berberrubine (BRB) as chemical constituents of some traditional Chinese medicines in human intestinal epithelial. By using Caco-2 (the human colonic adenocarcinoma cell lines) cell monolayers as an intestinal epithelial cell model, the permeability of COP and BRB were studied from apical side (AP side) to basolateral side (BL side) or from BL side to AP side. The two alkaloids were measured by reversed-phase high performance liquid chromatography (HPLC) coupled with UV detector. Transport parameters and apparent permeability coefficients (P(app)) were then calculated and compared with those of propranolol and atenolol. P(app) values were also compared with the reported values for model compounds (propranolol and atenolol). The P(app) values of COP, BRB were (1.103 +/- 0.162) x 10(-5), (1.309 +/- 0.102) x 10(-5) cm x s(-1 from AP side to BL side, and (0.300 +/- 0.041) x 10(-5) and (1.955 +/- 0.055) x 10(-5) cm x s(-1) from BL side to AP side, respectively. Their P(app) values were identical with those of propranolol [(2.23 +/- 0.10) x 10(-5 cm x s(-1)], which is a transcellular transport marker and as a control substance for high permeability. On the other hand, the efflux transport of BRB was higher 1.49 times more than its influx transport with 0.67 rate of P(app A-->B)/P(app B-->A). But P(app A-->B)/P(app B-->A value of COP was 3.67, which suggested that the efflux transport have not been involved in its absorbed mechanism in Caco-2 cells monolayers. COP and BRB can be absorbed across intestinal epithelial cells, and they are completely absorbed compounds. BRB may have been involved in efflux mechanism in Caco-2 cells monolayers model from the basolateral-to-apical direction.|To determine the pharmacokinetics, distribution, and mutual transformation of the total alkaloids, jatrorrhizine, coptisine, berberine, and palmatine from Coptis chinensis in rats. After the total alkaloids and berberine were fed into rats, their contents in plasma, tissues and gastrointestinal tract were determined by reversed-phase HPLC. The peak times of berberine in blood were 2.0 hr (Cmax 3.7 mg x L(-1)) and 5.0 hr Cmax 2.8 mg x L(-1)), respectively. Berberine in rat blood can be transformed into jatrorrhizine. After the rats were fed with the total alkaloids by gavage, the content of berberine was decreased monotonously, while coptisine, palmatine, and jatrorrhizine contents were increased gradually in the stomach, it speculated that berberine may be transformed into jatrorrhizine in the stomach. Animal experiments showed that berberine and palmatine were mainly distributed in the lungs of animals, followed by the distribution in the liver, while jatrorrhizine and coptisine was mainly in the liver, then in the lungs. Berberine could transform into jatrorrhizine. The mechanism on the appearance of two maximum blood concentration of berberine in blood could be explained with the propulsion of the gastrointestinal tract partly.|The absorption and transport mechanisms of berberine, palmatine, jateorhizine, and coptisine were studied using a Caco-2 cells uptake and transport model, with the addition of cyclosporin A and verapamil as P-glycoprotein (P-gp) inhibitors and MK-571 as a multidrug resistance-associated protein 2 (MRP(2)) inhibitor. In the uptake experiment, berberine, palmatine, jateorhizine, and coptisine were all taken into Caco-2 cells, and their uptakes were increased in the presence of cyclosporin A or verapamil. In the transport experiment, P(app) (AP-BL) was between 0.1 and 1.0 x 10(6) cm/sec for berberine, palmatine, jateorhizine, and coptisine and was lower than P(app) (BL-AB). ER values were all >2. Cyclosporin A and verapamil both increased P(app) (AP-BL) but decreased P(app) (BL-AB) for berberine, palmatine, jateorhizine, and coptisine; ER values were decreased by >50%. MK-571 had no influence on the transmembrane transport of berberine, palmatine, jateorhizine, and coptisine. At a concentration of 1-100 uM, berberine, palmatine, jateorhizine, and coptisine had no significant effects on the bidirection transport of Rho123. Berberine, palmatine, jateorhizine, and coptisine were all P-gp substrates; and at the range of 1-100 uM, berberine, palmatine, jateorhizine, and coptisine had no inhibitory effects on P-gp.|Jiao-Tai-Wan (JTW), an important herbal formula consists of Rhizoma coptidis and Cortex cinnamomi powder, is a famous prescription which has been used for centuries to treat insomnia in Traditional Chinese Medicine. The purpose of this study is to compare the pharmacokinetic properties of five protoberberine-type alkaloids (i.e. berberine, palmatine, coptisine, epiberberine and jatrorrhizine), the main bioactive constituents in JTW, between normal and insomnic rats. We also investigate the differences between single-dose and multiple-dose pharmacokinetics of five protoberberine-type alkaloids. The insomnic rat models were induced by intraperitoneal injection of one-dose para-chlorophenylalanine acid (PCPA). Quantification of five protoberberine-type alkaloids in rat plasma was achieved by using a rapid LC-MS/MS method. Plasma samples were collected at different time points to construct pharmacokinetic profiles by plotting drug concentration versus time and estimate pharmacokinetic parameters. An unpaired Student's t test was used for comparisons with SPSS 17.0. The five protoberberine-type alkaloids of single-dose normal groups had slow absorption and low bioavailability, as well as a delay of peak time. In the single-dose oral administration, the Cmax and Tmax of five ingredients in insomnic rats had significant differences compared with those of normal rats. In the multiple-dose oral administration, the pharmacokinetic parameters of five protoberberine-type alkaloids varied greatly in insomnic rats. In the normal rats, there were significant differences (p<0.05) in the principal pharmacokinetic parameters such as Cmax and Tmax between single-dose and multiple-dose oral administration. In the insomnic rats, the five ingredients of multiple-dose groups showed better absorption than the single-dose groups. Particularly, three peaks were observed in multiple-dose model group of plasma-concentration curves. The pharmacokinetic behavior of five protoberberine-type alkaloids was described in this paper. In both normal groups and model groups, the pharmacokinetic behavior of multiple-dose had significant differences comparing with the single-dose; either single-dose or multiple-dose, the pharmacokinetic behavior of insomnic rats had significant differences comparing the normal rats. Multiple dosing may improve the absorption of JTW in insomnic rats, which will increase the bioavailability and bring into active role in therapeutical effect.

/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 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 TKO. Use 0.9% saline (NS) or lactated Ringer's (LR) 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 (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/ALTERNATIVE and IN VITRO TESTS/ The crude extract (80% MeOH in water) of Chelidonii herba exhibited very interesting cytotoxicity against brine shrimp (Artemia salina Leach) nauplii and cultured human tumor cell in vitro, the colon carcinoma HT 29 (144 hr treatment). Fractionation of the crude extract and bioassay-guided procedures showed that the cytotoxic and the antitumor activities were concentrated in the basic extract. On the basis of IR, MS, and (1)H NMR the compound responsible of the cytotoxic activity was determined to be coptisine. Cytotoxicity evaluation of coptisine was next extended to a panel of human and murine cell lines in comparison with the established antitumor drugs mitoxantrone, doxorubicin (Dx) and cisplatin (CDDP). Coptisine was cytotoxic on LoVo and HT-29 and less potent on L-1210, and it was partially crossresistant on the human tumor colon cell line resistant to Dx, LoVo/Dx, whereas it was not significantly crossresistant on the murine leukemia cell line resistant to CDDP, L-1210/CDDP. Coptisine alkaloid was then synthesized in gram amount from commercial berberine. A four-step synthetic route was elaborated. The overall yield was about 8-10%. The structural identity of synthetic coptisine was verified by IR and NMR methods. A comparison of the cytotoxic effects on the human tumor colon cell line LoVo and on the murine leukemia L-1210 showed, for both natural and synthetic coptisines, a comparable cytotoxic activity more evident against HT-29 cell line and LoVo cell line, while the activity was lower against the L-1210 cell line.|/ALTERNATIVE and IN VITRO TESTS/ Acceleration of vascular smooth muscle cell (VSMC) proliferation is closely linked to the pathogenesis of vascular diseases. We, therefore, focused on traditional Japanese herbal medicines (Kampo medicines) used to ameliorate the impairment of microcirculation or blood stasis and screened them for their ability to inhibit rat VSMC proliferation. Among them, Unsei-in was found to effectively suppress VSMC proliferation, and Coptis rhizome was the responsible constituent crude drug. The extract of Coptis rhizome inhibited VSMC proliferation with the GI(50) value of 4.4 ug/mL, which was much lower than those against the proliferation of 3Y1, dRLh-84, B16, and HeLa cells. The Coptis rhizome extract inhibited the progression of VSMC arrested at G(0)/G(1) phase from G(0)/G(1) to S phase, but not that of 3Y1 cells. Biological assay-guided fractionation revealed that an alkaloid of Coptis rhizome, coptisine, was the active ingredient in selectively preventing VSMC proliferation with GI(50) of 3.3 uM (1.2 ug/mL). When the structurally-related isoquinoline alkaloids of protoberberine class were studied for their inhibitory activities, berberine decreased the VSMC proliferation with GI(50) of 95.1 microM (35.4 ug/mL), about 30 times higher concentration than coptisine, while palmatine failed to show any activity. This study provides evidence that coptisine, an ingredient of Unsei-in, prevents VSMC proliferation selectively at lower concentrations compared with various cells or other structurally related alkaloids.|/ALTERNATIVE and IN VITRO TESTS/ AIM: To investigate the cytotoxic effects of the six protoberberine alkaloids (PAs) from Rhizoma Coptidis on HepG2 cells. METHOD: A systematic screening was conducted to investigate the dynamic response of HepG2 cells to the PAs using the impedance-based xCELLigence system. Cisplatin was selected as the positive control. The real time, concentration-response curves and the 50% inhibitory concentrations (IC50) were acquired to evaluate the anticancer activity of the PAs. RESULTS: All of the six PAs inhibited cell growth and induce death in HepG2 cells in a time- and concentration-dependent manner. The IC50 values of cisplatin, berberine, columbamine, coptisine, epiberberine, jatrorrhizine, and palmatine were 5.13, 42.33, 226.54, 36.90, 302.72, 383.54, and 456.96 ugxmL(-1), respectively. The results obtained using the xCELLigence system corresponded well with those of the conventional methods. CONCLUSION: The xCELLigence system is a reliable and efficient tool for real-time screening of the cytotoxic effect of compounds in cell-based in vitro assays. Coptisine and berberine, with methylenedioxy group at C2 and C3 on the phenyl ring showed stronger effect.than the other four PAs. However, compared with cisplatin, the six PAs didn't show obvious cytotoxic effect on HepG2 cells. These results provided some useful data for the evaluation of the anticancer compounds, and the clinical application of traditional Chinese medicine.|/ALTERNATIVE and IN VITRO TESTS/ To study the effect of cholesterol and 25-OH-cholesterol on cholesterol metabolism in HepG2 cells and the effect of coptisine (Cop) extracted from Coptidis Rhizoma (CR) in reducing and regulating cholesterol. In this study, TC, TG, LDL-c, and HDL-c were measured by biochemical analysis; mRNA and protein expressions of LDLR, HMGCR, and CYP7A1 were detected by qRT-PCR and Western blot. According to the results, cholesterol and 25-OH-cholesterol inducing could decrease in mRNA and protein expressions of LDLR and CYP7A1, so as to increase TC and LDL-c contents. However, Cop could up-regulate mRNA and protein expressions of LDLR and CYP7A1 and down-regulate that of HMGCR, so as to reduce TC and LDL-c levels. These findings suggested that Cop has potential pharmacological activity for reducing cholesterol, and may reduce cholesterol by regulating mRNA and protein expressions of key genes involved in cholesterol metabolism, such as LDLR, CYP7A1, and HMGCR.|For more Human Toxicity Excerpts (Complete) data for Coptisine (7 total), please visit the HSDB record page.

7,8,13,13a-tetradehydro-2,3-9,10-bis(methylenedioxy)berbinium

A poison|Coptisine, a cytotoxic alkaloid found in Chinese goldthread, is related to berberine. It has been analyzed as a cytotoxic agent in heptoma and leukemic cells and is reported to block cell cycle progression.

The simultaneous determination of berberine, palmatine, coptisine, epiberberine, and jatrorrhizine in rat plasma by LC-MS/MS and a pharmacokinetic comparison after the oral administration of Rhizoma coptidis and Jiao-Tai-Wan extract.