benzofurans and inermin

This study aims to characterize the pharmacokinetic (PK) profiles and identify important bioavailability barriers and pharmacological pathways of the key active components (KACs) of Antitumor B (ATB), a chemopreventive agent. KACs (matrine, dictamine, fraxinellone, and maackiain) of ATB were confirmed using the antiproliferative assay and COX-2 inhibition activities in oral cancer cells. The observed

Topics: Alkaloids; Animals; Benzofurans; Biological Availability; Chemoprevention; Drugs, Chinese Herbal; Matrines; Mice; Mice, Inbred C57BL; Molecular Structure; Mouth Neoplasms; Network Pharmacology; Pterocarpans; Quinolines; Quinolizines

1. SKI3301, a standardized dried 50% ethanolic extracts of Sophora tonkinensis, contains four marker compounds (trifolirhizin, TF; (-)-maackiain, Maack; (-)-sophoranone, SPN, and (2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran, ABF), is being developed as an herbal medicine for the treatment of asthma in Korea. This study investigates the pharmacokinetic properties of SKI3301 extract in rats. 2. The dose-proportional AUCs suggest linear pharmacokinetics of TF, Maack, SPN and ABF in the SKI3301 extract intravenous dose range of 5-20 mg/kg. After the oral administration of 200-1000 mg/kg of the extract, TF and Maack exhibited non-linearity due to the saturation of gastrointestinal absorption. However, linear pharmacokinetics of SPN and ABF were observed. 3. The absorptions of TF, Maack, SPN and ABF in the extract were increased relative to those of the respective pure forms due to the increased solubility and/or the decreased metabolism by other components in the SKI3301 extract. 4. No accumulation was observed after multiple dosing, and the steady-state pharmacokinetics of TF, Maack, SPN and ABF were not significantly different from those after a single oral administration of the extract. 5. The pharmacokinetics of TF, SPN and ABF were not significantly different between male and female rats after oral administration of the extract, but a significant gender difference in the pharmacokinetics of Maack in rats was observed. 6. Our findings may help to comprehensively elucidate the pharmacokinetic characteristics of TF, Maack, SPN and ABF and provide useful information for the clinical application of SKI3301 extract.

Topics: Administration, Intravenous; Administration, Oral; Animals; Area Under Curve; Benzofurans; Dose-Response Relationship, Drug; Female; Flavonoids; Glucosides; Half-Life; Heterocyclic Compounds, 4 or More Rings; Intestinal Absorption; Male; Plant Extracts; Plant Roots; Pterocarpans; Rats; Sex Characteristics; Solubility; Sophora

Zeng-Sheng-Ping (ZSP), also called antitumor B, is a marketed Chinese traditional medicine used for cancer prevention.. Currently, for the quality control of Chinese traditional medicines, marker compounds are not selected based on bioactivities and pharmaceutical behaviors in most of the cases. Therefore, even if the "quality" of the medicine is controlled, the pharmacological effect could still be inconsistent. The aim of this study is to establish an activity and absorption-based platform to select marker compound(s) for the quality control of Chinese traditional medicines.. We used ZSP as a reference Chinese traditional medicine to establish the platform. Activity guided fractionation approach was used to purify the major components from ZSP. NMR and MS spectra were used to elucidate the structure of the isolated compounds. MTT assay against oral carcinoma cell line (SCC2095) was performed to evaluate the activities. UPLC-MS/MS was used to quantify the pure compounds in ZSP and the active fraction. The permeabilities of the identified compounds were evaluated in the Caco-2 cell culture model. The intracellular accumulation of the isolated compounds was evaluated in the SCC2095 cells.. The major compounds were identified from ZSP. The contents, anti-proliferation activities, permeabilities, and intracellular accumulations of these compounds were also evaluated. The structure of these purified compounds were identified by comparing the NMR and MS data with those of references as rutaevine (1), limonin (2), evodol (3), obacunone (4), fraxinellone (5), dictamnine (6), maackiain (7), trifolirhizin (8), and matrine (9). The IC50 of compounds 5, 6, and 7 against SCC2095 cells were significantly lower than that of ZSP. The uptake permeability of compounds 5, 6, and 7 were 2.58 ± 0.3 × 10(-5), 4.33 ± 0.5 × 10(-5), and 4.27 ± 0.8 × 10(-5) respectively in the Caco-2 cell culture model. The intracellular concentrations of these compounds showed that compounds 5, 6, and 7 were significantly accumulated inside the cells.. Based on the activity against oral carcinoma cell line as well as the absorption permeability, compound 5, 6, and 7 are selected as quality control markers for ZSP. An activity and absorption-based platform was established and successfully used for the quality control of ZSP.

Topics: Alkaloids; Benzofurans; Benzoxepins; Cell Line, Tumor; Cell Proliferation; Drugs, Chinese Herbal; Glucosides; Heterocyclic Compounds, 4 or More Rings; Humans; Limonins; Matrines; Medicine, Chinese Traditional; Permeability; Pterocarpans; Quality Control; Quinolines; Quinolizines; Triterpenes

A new liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of trifolirhizin, (-)-maackiain, (-)-sophoranone, and 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran from Sophora tonkinensis in rat plasma using chlorpropamide as an internal standard. Plasma samples (50 μL) were prepared using a simple deproteinization procedure with 150 μL of acetonitrile containing 100 ng/mL of chlorpropamide. Chromatographic separation was carried out on an Acclaim RSLC120 C18 column (2.1 × 100 mm, 2.2 μm) using a gradient elution consisting of 7.5 mM ammonium acetate and acetonitrile containing 0.1% formic acid (0.4 mL/min flow rate, 7.0 min total run time). The detection and quantitation of all analytes were performed in selected reaction monitoring mode under both positive and negative electrospray ionization. This assay was linear over concentration ranges of 50-5000 ng/mL (trifolirhizin), 25-2500 ng/mL ((-)-maackiain), 5-250 ng/mL ((-)-sophoranone), and 1-250 ng/mL 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran) with a lower limit of quantification of 50, 25, 5, and 1 ng/mL for trifolirhizin, (-)-maackiain, (-)-sophoranone, and 2-(2,4-dihydroxyphenyl)-5,6-methylenedioxybenzofuran, respectively. All the validation data, including the specificity, precision, accuracy, recovery, and stability conformed to the acceptance requirements. The results indicated that the developed method is sufficiently reliable for the pharmacokinetic study of the analytes following oral administration of Sophora tonkinensis extract in rats.

Topics: Acetates; Acetonitriles; Animals; Benzodioxoles; Benzofurans; Blood Chemical Analysis; Calibration; Chromatography, Liquid; Flavonoids; Formates; Glucosides; Heterocyclic Compounds, 4 or More Rings; Limit of Detection; Linear Models; Male; Plant Extracts; Pterocarpans; Quality Control; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sophora; Tandem Mass Spectrometry

To study the chemical constituents from the root of Millettia speciosa.. To isolate and purify by silica gel, macroporous resin D-101 and Sephadex LH-20.. Five compounds were isolated from 95% EtOH extract of Millettia Speciosa and their structures were elucidated by physico-chemical properties and spectroscopic analysis as Isoliquiritigenin (I), Maackiain (II), Pterocarpin (III), Medicarpin (IV) and Homopterocarpin (V).. Compounds I, III are obtained from this plant for the first time, compounds V is isolated from the genus Millettia for the first time.

Topics: Benzofurans; Benzopyrans; Chalcones; Ethanol; Magnetic Resonance Spectroscopy; Millettia; Molecular Structure; Plant Roots; Plants, Medicinal; Pterocarpans

The ether soluble fraction of the roots of Ononis vaginalis Vahl. Symb. afforded three new compounds: 3-hydroxy-4,9-dimethoxycoumestan, maginaldehyde [2-(4-hydroxy-2-methoxyphenyl)-5,6-dimethoxy-3-benzofuran-carboxaldehyde] and 5,7,4'-trihydroxy-4-styrylcoumarin. In addition, four known pterocarpans; 3,4,9-trimethoxypterocarpan, maackiain, medicarpin and trifolirhizin were also isolated. The styrylcoumarin derivative showed significant antiviral activity against Herpes simplex type 1 and weak cytotoxicity.

Topics: Antiviral Agents; Benzofurans; Benzopyrans; Coumarins; Herpesvirus 1, Human; Magnetic Resonance Spectroscopy; Medicine, Traditional; Molecular Structure; Phenols; Plant Extracts; Plant Roots; Pterocarpans; Spectrophotometry, Infrared

Phytoalexins are low molecular weight antibiotic compounds produced by plants in response to infection by microbes. These antimicrobial compounds are thought to provide resistance to microbial invasion and colonization. (-)Maackiain and its pterocarpan relatives can be oxidized at a number of sites, including at the 6 carbon. A previously unknown metabolite was produced for (-)maackiain by the broad host-range pathogen Colletotrichum gloeosporioides (Glomerella cingulata). This unknown was identified by LC-MS-MS and NMR spectroscopy to be 6,6a-di-OH-maackiain (3,6,6a-trihydroxy-8,9,methylenedioxy-pterocarpan). It is produced by isolates that represent all four races and pathotypes of C. gloeosporioides isolated from the tropical forage legume Stylosanthes spp. We present evidence that the primary metabolite (-)6a-OH-maackiain is subsequently hydroxylated at carbon 6, a step resulting in a compound that is increased in polarity and decreased in toxicity relative to the parent compound and (-)6a-OH-maackiain. This further oxidation may be required for efficient excretion or carbon source scavenging.

Topics: Benzofurans; Benzopyrans; Mitosporic Fungi; Molecular Structure; Oxidation-Reduction; Phytoalexins; Plant Extracts; Plant Roots; Plants; Poaceae; Pterocarpans; Sesquiterpenes; Terpenes