oxysophocarpine and oxymatrine

Radix Sophorae flavescentis is generally used for the treatment of different stages of prostate cancer in China. It has ideal effects when combined with surgical treatment and chemotherapy. However, its active components are still ambiguous. We devised a comprehensive two-dimensional PC-3 prostate cancer cell membrane chromatography system for screening anti-prostate cancer components in Radix Sophorae flavescentis. Gefitinib and dexamethasone were chosen as positive and negative drugs respectively for validation and optimization the selectivity and suitability of the comprehensive two-dimensional chromatographic system. Five compounds, sophocarpine, matrine, oxymatrine, oxysophocarpine, and xanthohumol were found to have significant retention behaviors on the PC-3 cell membrane chromatography and were unambiguously identified by time-of-flight mass spectrometry. Cell proliferation and apoptosis assays confirmed that all five compounds had anti-prostate cancer effects. Matrine and xanthohumol had good inhibitory effects, with half maximal inhibitory concentration values of 0.893 and 0.137 mg/mL, respectively. Our comprehensive two-dimensional PC-3 prostate cancer cell membrane chromatographic system promotes the efficient recognition and rapid analysis of drug candidates, and it will be practical for the discovery of prostate cancer drugs from complex traditional Chinese medicines.

Topics: Alkaloids; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Cell Membrane; China; Chromatography, High Pressure Liquid; Drug Screening Assays, Antitumor; Drugs, Chinese Herbal; Flavonoids; Humans; Male; Matrines; Propiophenones; Prostatic Neoplasms; Quinolizines; Sophora

The matrine-type alkaloid, oxymatrine inhibits hepatitis B virus (HBV) replication but very little is known about these effects in other matrine-type alkaloids, including sophoridine and sophocarpine. Therefore, we compared the in vitro anti-HBV effects of matrine, oxymatrine, sophocarpine, and sophoridine by treating an HBV-transfected cell line (HepG2.2.15) with 0.4-1.6mM of the compounds for 24 or 72h. The levels of the HBV surface antigen (HBsAg) and e antigen (HBeAg) in the culture medium, as well as the intracellular and extracellular HBV DNA levels, were determined. Metabolomic analysis and detection of the mRNA level of p38 mitogen-activated protein kinase (MAPK), tumor necrosis factor receptor-associated factor (TRAF) 6, extracellular signal-regulated kinase (ERK) 1, NOD-like receptor family pyrin domain containing 10 (NLRP10), and caspase-1 were conducted in sophoridine-treated HepG2.2.15 cells. HepG2.2.15 cell exposure to 0.4-1.6mM sophocarpine or sophoridine for 24h reduced the HBsAg level of the medium more effectively than exposure to matrine and oxymatrine did, and reduced the HBeAg levels more effectively than these compounds did at 1.6mM. Sophoridine (0.4-1.6mM) reduced the cell medium HBV DNA levels more than the same concentrations of matrine, oxymatrine, or sophocarpine did. After 72h, 0.4 and 0.8mM sophoridine reduced HBsAg and intracellular HBV DNA levels more potently than matrine, oxymatrine, or sophocarpine did. Furthermore, sophoridine (0.8mM) potently reduced the cell medium HBeAg levels while the metabolomic analyses revealed that HepG2.2.15 cells exposed to 0.8mM sophoridine for 72h exhibited reduced cycloleucine and phytosphingosine levels. In addition, the mRNA expression analyses revealed that HepG2.2.15 cells exposed to 0.8mM sophoridine showed reduced levels of p38 MAPK, TRAF6, ERK1, NLRP10, and caspase-1. Sophoridine produced more potent anti-HBV effects than matrine, oxymatrine, and sophocarpine did. These effects may be related to the sophoridine-mediated reduction of p38 MAPK and TRAF6 levels.

Topics: Alkaloids; Antiviral Agents; Cell Line; Culture Media; Cytoplasm; DNA, Viral; fas Receptor; Gene Expression Profiling; Hepatitis B e Antigens; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatocytes; Host-Pathogen Interactions; Humans; Matrines; Metabolome; p38 Mitogen-Activated Protein Kinases; Quinolizines; Virus Replication

Three new matrine-type alkaloids, (+)-5α-hydroxyoxysophocarpine (1), (-)-12β-hydroxyoxysophocarpine (2), and (+)-5α-hydroxylemannine (3), along with 14 known analogues, (-)-sophocarpine (4), (-)-5α-hydroxysophocarpine (5), (-)-9α-hydroxysophocarpine (6), (+)-12α-hydroxysophocarpine (7), (-)-12β-hydroxysophocarpine (8), (+)-oxysophocarpine (9), (+)-matrine (10), (+)-sophoranol (11), (+)-9α-hydroxymatrine (12), (-)-14β-hydroxymatrine (13), (+)-oxymatrine (14), (+)-5α-hydroxyoxymatrine (15), (-)-14β-hydroxyoxymatrine (16), and (+)-sophoramine (17), were isolated from the rhizomes of Sophora tonkinensis. Their structures were elucidated via spectrometric data analyses, and the absolute configurations were established by single-crystal X-ray diffraction and ECD data. Alkaloids 2, 6, 11, and 13 exhibited antiviral activity against the Coxsackie virus B3 (CVB3), with IC50 values of 26.62-252.18 μM, and alkaloids 7, 8, and 17 inhibited influenza virus A/Hanfang/359/95 (H3N2) replication with IC50 values of 63.07-242.46 μM.

Topics: Alkaloids; Antiviral Agents; Influenza A Virus, H3N2 Subtype; Inhibitory Concentration 50; Matrines; Molecular Structure; Quinolizines; Rhizome; Sophora; Stereoisomerism

A rapid NIRS method for determination of macrozamin in Heterosmilacis japonicae rhizoma (HJR), and the total content of oxymatrine and matrine (OMT + MT) as well as the total content of oxysophocarpine and sophocarpine (OSC + SC) in sophorae flavescens radix (SFR) was developed to explore the application feasibility of NIRS for the quality assurance system of Chinese patent drugs. The contents of macrozamin in HJR samples, and OMT + MT and OSC + SC in SFR samples were determined by HPLC as reference values. The NIR spectra of the samples were measured in a diffused reflection mode. The different characteristic wavebands and pretreatment methods were optimized. The quantitative calibration models between the NIR spectra and the content reference values of marker components in HJR and SFR samples, were established with partial least square method, and further optimized through the cross validation and external validation. The contents of macrozamin in 88 batches of HJR samples were over the range of 0.36-12.88 mg · g(-1). The total contents of OMT + MT and OSC + SC in 75 batches of SFR samples were over the range of 8.87-66.31 and 2.30-15.11 mg · g(-1), respectively. The performance of the final models for macrozamin, OMT + MT and OSC + SC was evaluated well according to correlation coefficients (r), root mean square error of cross-validation (RMSECV) and root mean square error of prediction (RMSEP). The R2 values of the cross-validation for macrozamin, OMT + MT and OSC + SC were 0.9025, 0.9491 and 0.9137, and those of RMSECV were 0.961, 2.45 and 0.724 mg · g(-1) respectively. The R2 values of external validation for the three models were 0.9817, 0.9826 and 0.9609, and those of RMSEP were 0.693, 2.27 and 0.658 mg · g(-1), respectively. This is the first report on rapid determination of macrozamin in Heterosmilacis japonicae rhizoma, and oxymatrine, matrine, oxysophocarpine and sophocarpine in sophorae flavescens radix by NIRS method. The presented method can fulfill the requirement of rapid acquirement of chemical information of raw medicinal materials prior the manufacturing of compound Kushen injection.

Topics: Alkaloids; Calibration; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Least-Squares Analysis; Matrines; Plant Roots; Quinolizines; Smilacaceae; Sophora; Spectroscopy, Near-Infrared

In order to improve the resolution and peak shape, 1-butyl-3-methylimidazolium tetrafluoroborate ( [ BMIM] BF4 ) was used as mobile phase additive to develop an HPLC method for the determination of four main alkaloids in Compound Kushen Injection. An Agilent TC-C18 column was used with the mobile phase of methanol-0.1% phosphoric acid solution (containing 2. 2 x 10(4) mol/L [BMIM] BF4 ) (5: 95, v/v) , flow rate of 1.0 mL/min, column temperature of 30 degree C, and injection volume of 20 micro L, detected at 205 nm. The calibration curves of matrine, sophoridine, oxymatrine and oxysophocarpine were in good linearity over the ranges of 25.8 -155.0 mg/L, 40.0 -240.0 mg/L, 21.7 - 130.0 mg/L and 37.5 -225.0 mg/L, respectively, with correlation coefficients above 0. 999 0. The mean recoveries (n = 9) were between 96. 2% and 98.9%. Ionic liquid, [BMIM] BF4, can obviously improve the resolution and peak shape. The method is simple, rapid, and reliable, and can be used for the determination of alkaloids in Sophora flavescens Ait in Compound Kushen Injection.

Topics: Alkaloids; Chromatography, High Pressure Liquid; Drug Combinations; Drugs, Chinese Herbal; Ionic Liquids; Matrines; Quinolizines

To establish a new method for quality evaluation and validate its feasibilities by simultaneous quantitative assay of five alkaloids in Sophora flavescens.. The new quality evaluation method, quantitative analysis of multi-components by single marker (QAMS), was established and validated with S. flavescens. Five main alkaloids, oxymatrine, sophocarpine, matrine, oxysophocarpine and sophoridine, were selected as analytes to evaluate the quality of rhizome of S. flavescens, and the relative correction factor has good repeatibility. Their contents in 21 batches of samples, collected from different areas, were determined by both external standard method and QAMS. The method was evaluated by comparison of the quantitative results between external standard method and QAMS.. No significant differences were found in the quantitative results of five alkaloids in 21 batches of S. flavescens determined by external standard method and QAMS.. It is feasible and suitable to evaluate the quality of rhizome of S. flavescens by QAMS.

Topics: Alkaloids; Matrines; Quinolizines; Sophora

Matrine (MT)- and oxymatrine (OMT)-imprinted monodisperse polymers have been prepared by precipitation polymerization. The prepared molecularly imprinted polymers (MIPs) for MT and OMT, MIP(MT) and MIP(OMT), were monodispersed microspheres of 3.3 and 3.9 μm in diameter, respectively. Binding experiments and Scatchard analyses revealed that two classes of binding sites were formed on MIP(MT) and MIP(OMT). In addition to shape recognition, ionic and hydrophobic interactions seemed to affect the retention and recognition of MT and OMT on MIP(MT) and MIP(OMT), respectively, in low acetonitrile content, and ionic and hydrophilic interactions affected these properties in high acetonitrile content. MIP(MT) was used to selectively extract MT and sophocarpine (13,14-dehydromatrine) from Sophora flavescens root, while MIP(OMT) was used to extract OMT and oxysophocarpine (13,14-dehydrooxymatrine).

Topics: Alkaloids; Chemical Precipitation; Matrines; Molecular Imprinting; Plant Roots; Polymerization; Polymers; Quinolizines; Sophora

To establish a method for determination of 7 alkaloid in Herba Sophorae Alopecuroidis by HPLC.. X-Brige C18 (4.6 mm x 200 mm, 5 microm) column was used with acetonitriles-0.05 mol x L(-1) KH2PO4 solution (2.0 mL x L(-1) triethylamine) with gradient elution as the mobile phase and 1.0 mL x min(-1) as the flow rate. The detection wavelength was 205 nm.. Aloperin curve was linear in the range from 20.66 to 103.32 microg (r = 0.998 8) and the average recovery was 97.12% (RSD 7. 3%); sophoridine curve was linear in the range from 22.82 to 114.12 microg (r = 0.999 7) and the average recovery was 97.47% (RSD 3.0%); oxymatrine curve was linear in the range from 25.10 to 125.52 microg (r = 0.999 1) and the average recovery was 96.21% (RSD 4.5%); oxysophocarpine curve was linear in the range from 23.88 to 119.40 microg (r = 0.997 5) and the average recovery was 94. 64% (RSD 5.2%); matrine curve was linear in the range from 5.00 to 24.99 microg (r = 0.998 6) and the average recovery was 98.04% (RSD 5.4%); sophocarping curve was linear in the range from 4.69 to 23.46 microg (r = 0.999 6) and the average recovery was 96.24 (RSD 5.8%); lehmannine curve was linear in the range from 4.60 to 23.01 microg (r = 0.997 8) and the average recovery was 101.31% (RSD 4.3%).. The method is accurate, simple and feasible. It can be used as a quality evaluation in Herba S. Alopecuroidis.

Topics: Alkaloids; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Matrines; Piperidines; Quality Control; Quinolizidines; Quinolizines; Sophora

To establish an HPLC-MS method for simultaneous determination of matrine, oxymatrine and oxysophocarpine in rat plasma after oral administration of herbal preparation, namely Sanwu Huangqin decoction, and the pharmacokinetic porameters were calculated as well. Matrine, oxymatrine, oxysophocarpine, and internal standard pseudoephedrine were extracted from plasma with liquid-liquid extraction, then separated on a Kromasil C18 column by using acetonitrile-0.1% aqueous formic acid (10 : 90) as mobile phase. Electrospray ionization (ESI) source was applied and operated in positive ion mode. The linear calibration curve was obtained in the concentration range of 10 -5 000 ng x mL(-1) for matrine, 2 - 1 000 ng x mL(-1) for oxymatrine, and 2 - 1 000 ng x mL(-1) for oxysophocarpine. The extraction recovery was 89.1% - 93.5%, 83.9% - 91.3%, and 85.4% - 88.0% accordingly. The inter- and intra- day precision (RSD) was below 15.0% calculated from quality control (QC) samples. Matrine, oxymatrine and oxysophocarpine concentration time profile conformed to a two-compartment pharmacokinetic model. The method was shown to be effective, convenient, and suitable for simultaneous pharmacokinetic study of matrine, oxymatrine, and oxysophocarpine in rat.

Topics: Administration, Oral; Alkaloids; Animals; Area Under Curve; Chromatography, High Pressure Liquid; Drug Combinations; Drugs, Chinese Herbal; Male; Matrines; Plants, Medicinal; Quinolizines; Rats; Rats, Wistar; Spectrometry, Mass, Electrospray Ionization

A rapid, sensitive and selective high-performance liquid chromatography tandem mass spectrometric method (HPLC-MS) has been developed and validated for the simultaneous determination of matrine (MT), oxymatrine (OMT) and oxysophocarpine (OSP) in rat plasma after oral administration of Sophora flavescens Ait. extract using pseudoephedrine hydrochloride as an internal standard (I.S.). The three analytes were extracted from the plasma samples by liquid-liquid extraction with chloroform. The chromatographic separation was accomplished on a Kromasil C18 column (150 mm x 4.6 mm). Detection was performed on a single quadrupole mass spectrometer by selected ion monitoring (SIM) mode via electrospray ionization (ESI) source. The total run time was 12 min between injections. The assay had a lower limit of quantification of 1.0 ng/ml for MT, 2.0 ng/ml for OMT and 2.0 ng/ml for OSP using 200 microl of plasma. The calibration curves were linear in the measured range. The overall precision and accuracy for all concentrations of quality controls and standards was better than 15%. The proposed method enables unambiguous identification and quantification of MT, OMT and OSP in vivo. This was the first report on determination of the major quinolizidine alkaloids in rat plasma after oral administration of Sophora flavescens Ait. extract. The results provided a meaningful basis for evaluating the clinical applications of the herbal medicine.

Topics: Administration, Oral; Alkaloids; Animals; Area Under Curve; Calibration; Chromatography, High Pressure Liquid; Drug Stability; Freezing; Half-Life; Male; Matrines; Molecular Structure; Plant Extracts; Quality Control; Quinolizines; Rats; Rats, Wistar; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Sophora; Tandem Mass Spectrometry; Time Factors

To establish a suitable dosage form for a traditional anti-anaphylaxis Chinese medicine of Kushen recipe, and investigate the effect of cutaneous permeation in vitro of the recipe.. Techniques of extracting with ethanol and purifying with absorbent resin to obtain alkaloids from Kushen recipe were adopted, while volatile oil was extracted by steam distillation. The extraction was made to gel. The skin from SD rats' abdomen was used as permeability barriers. Then effects of permeation of the aqueous extraction, the purifying extraction and the gel were compared by Valia-Chien and Franz diffusion cell method. HPLC was utilized to quantitate the alkaloids in permeating liquid.. In view of the permeation cumulation quantity, the permeation velocity and the lag time of the four kinds of alkaloids, the effect of permeation of purifying extraction was better than the aqueous extraction, and the purifying extraction gel surpassed both the aqueous extraction and the purifying extraction.. It was certified that the purifying extraction gel had improved the effect of cutaneous permeation of alkaloids, and it is the befitting dosage form for Kushen recipe to treat anaphylaxis disease in skin.

Topics: Administration, Cutaneous; Alkaloids; Animals; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Female; Gels; In Vitro Techniques; Matrines; Quinolizines; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Skin; Skin Absorption

To develop a HPLC method for simultaneous determination of the contents of sophoridine, oxymatrine and oxysophocarpine in seed of Sophora alopecuroides.. Chromatographic condition included a Phenomenex Gemini C18 (4.6 mm x 250 mm, 5 microm) column and thmobile phase consisting of a mixture of methanol-0.2% phosphatic acid (7:93). The detection wavelength was at 205 nm. The flow rate was 1.0 mL x min(-1) and column temperature was set at 30 degrees C.. All calibration curves showed good linearity (r > or = 0.9997) within test ranges. The mean recoveries were 100.0%, 97.0% and 97.0% respectively.. This method is simple, rapid and accurate, and suitable for quality control of S. alopecuroides seed.

Topics: Alkaloids; Chromatography, High Pressure Liquid; Matrines; Plants, Medicinal; Quality Control; Quinolizines; Reproducibility of Results; Seeds; Sophora

To determine oxymatrine content and its related substances in oxymatrine capsule.. A HPLC method was adopted. C18 column was used. The mobile phase consisted of phosphate buffer solution-methanol (85:15). The UV detective wavelength was 210 nm.. The calibration curve of oxymatrine was linear in the range of 6.952 - 20.856 microg/ml (r = 0.9999). The calibration curve of N-oxysophocarpine was linear in the range of 0.1837 - 0.5510 microg/ml (r = 0.9997).. The method is simple, rapid and accurate.

Topics: Alkaloids; Antiviral Agents; Capsules; Chromatography, High Pressure Liquid; Drug Combinations; Drugs, Chinese Herbal; Plants, Medicinal; Quality Control; Quinolizines

Seven alkaloids were isolated from the seed of Sophora alopecuroides and identified to be oxymatrin, oxysophocarpine, cytisine, matrine, sophocarpine, sophoridine and nicotine respectively by comparing chromactographic and spectral characteristics with authentic known compounds. Nicotine was isolated from Sophora for the first time. The activity of extracts and alkaloids against cancer, virus, dermatophytes and bacteria was carried out in vitro.

Topics: Alkaloids; Anti-Bacterial Agents; Anti-Infective Agents; Antineoplastic Agents, Phytogenic; Cystine; Drugs, Chinese Herbal; Fabaceae; Lung Neoplasms; Matrines; Nicotine; Plants, Medicinal; Quinolizines; Seeds; Tumor Cells, Cultured

Six alkaloids were isolated from the mature seeds of Sophora viciifolia for the first time. On the basis of physicochemical and spectroscopic analysis, their structures have been identified as oxymatrine, oxysophocarpine, matrine, sophocarpine, sophoramine and sophoridine.

Topics: Alkaloids; Drugs, Chinese Herbal; Fabaceae; Plants, Medicinal; Quinolizines

Topics: Alkaloids; Anthelmintics; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Densitometry; Fabaceae; Matrines; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Naphthyridines; Phytotherapy; Plants, Medicinal; Quinolizines