bavachin and bavachinin

A method for the simultaneous quantification of 13 bioactive compounds (psoralen, isopsoralen, isobavachin, bakuchalcone, neobabaisoflavone, bavachin, corylin, psoralidin, isobavachalcone, bavachinin, corylifol A, bavachalcone, and bakuchiol) by ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry has been developed and validated in rat plasma. Osthol was used as an internal standard and plasma samples were pretreated with one-step liquid-liquid extraction. These analytes were separated using a gradient mobile phase system of water and acetonitrile at a flow rate of 0.2 mL/min on a reverse-phase C18 column and analyzed in the selected multiple reactions monitoring mode. All calibration curves were linear (r > 0.9952) over the tested ranges. The intra- and interday accuracy and precisions of these analytes at three different concentration levels were within the acceptable limits of <15% at all concentrations. The mean recoveries of these analytes at three concentrations were more than 60.2% and the matrix effects were in the range of 85-115%. Stability studies proved that the analytes were stable under the tested conditions. The developed method was applied to evaluating the pharmacokinetic study of 13 bioactive compounds after oral administration of Psoraleae Fructus in rat of different genders. Some active compounds in Psoraleae Fructus had sex-related pharmacokinetics.

Topics: Animals; Benzofurans; Chalcones; Chromatography, High Pressure Liquid; Coumarins; Female; Ficusin; Flavones; Flavonoids; Furocoumarins; Male; Mass Spectrometry; Molecular Structure; Phenols; Psoralea; Rats; Rats, Sprague-Dawley

Enhancing the surface area of stationary phase is essential in chromatographic science. In this work, nanoscale NiAl-layered double hydroxides (NiAl-LDHs) with flower-like structure was used as a platform for supporting the stationary phase. Then strong hydrophobic p-naphtholbenzein molecule was immobilized onto the LDHs layer as sorbent for stir bar sorptive extraction (SBSE). The flower-like LDHs layer significantly increased the extraction efficiency through increasing the specific surface area and immobilized amounts of stationary phase. In addition, the LDHs can also provide anion exchange ability, which expanded the application of this stir bar for analysis of not only hydrophobic but also anionic analytes. For improving the workability, a poly(ether ether ketone) (PEEK) jacket stir bar with detachable dumbbell-shaped structure was employed. The PEEK jacket with high mechanical strength and dumbbell-shaped structure improved the durability of stir bar and the detectable design allowed elution to be realized with less solvent that enhanced the enrichment factor. The proposed stir bar showed good performance for the extraction of multiple analytes including flavonoids, non-steroid anti-inflammatory drugs and chlorophenoxy acids. By coupling with high performance liquid chromatography-ultraviolet detection (HPLC-UV), the SBSE-HPLC-UV method was applied for the extraction of three active components including bavachin, isobavachalcone and bavachinin in Psoralea corylifolia L. herb with low limit detection of 0.01-0.02 ng/mL.

Topics: Adsorption; Chalcones; Chromatography, High Pressure Liquid; Flavonoids; Hydroxides; Limit of Detection; Naphthols; Psoralea; Reproducibility of Results; Solid Phase Extraction; Spectrophotometry, Ultraviolet

A library of 28 analogs of bavachinin including aliphatic and aromatic ethers, epoxide, chalcone, oxime, semicarbazide, oxime ether and triazole derivatives have been synthesized and evaluated for cytotoxicity against four different human cancer cell lines. Bio-evaluation studies exhibited better cytotoxic profile for many analogs compare to bavachinin. Best results were observed for a 1,2,3-triazole analog (17i) with IC

Topics: Antineoplastic Agents; Cell Movement; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Flavonoids; Humans; Membrane Potential, Mitochondrial; Molecular Structure; Structure-Activity Relationship; Tumor Cells, Cultured

As an edible traditional Chinese herb, Fructus psoraleae (FP) has been widely used in Asia for the treatment of vitiligo, bone fracture and osteoporosis. Several cases on markedly elevated bilirubin and acute liver injury following administration of FP and its related proprietary medicine have been reported, but the mechanism in FP-associated toxicity has not been well investigated yet. This study aimed to investigate the inhibitory effects of FP extract and its major constituents against human UDP-glucuronosyltransferase 1A1 (UGT1A1), the key enzyme responsible for metabolic elimination of bilirubin. To this end, N-(3-carboxy propyl)-4-hydroxy-1,8-naphthalimide (NCHN), a newly developed specific fluorescent probe for UGT1A1, was used to evaluate the inhibitory effects of FP extract or its fractions in human liver microsomes (HLM), while LC-UV fingerprint and UGT1A1 inhibition profile were combined to identity and characterize the naturally occurring inhibitors of UGT1A1 in FP. Our results demonstrated that both the extract of FP and five major components of FP displayed evident inhibitory effects on UGT1A1 in HLM. Among these five identified naturally occurring inhibitors, bavachin and corylifol A were found to be strong inhibitors of UGT1A1 with the inhibition kinetic parameters (Ki) values lower than 1 μM, while neobavaisoflavone, isobavachalcone, and bavachinin displayed moderate inhibitory effects against UGT1A1 in HLM, with the Ki values ranging from 1.61 to 9.86μM. These findings suggested that FP contains natural compounds with potent inhibitory effects against human UGT1A1, which may be one of the important reasons for triggering FP-associated toxicity, including elevated bilirubin levels and liver injury.

Topics: Bilirubin; Chalcones; Chemical and Drug Induced Liver Injury; Dose-Response Relationship, Drug; Flavones; Flavonoids; Fruit; Glucuronosyltransferase; Humans; Isoflavones; Liver; Microsomes, Liver; Plant Extracts; Psoralea

A simple and effective neuraminidase-immobilized capillary microreactor was fabricated by glutaraldehyde cross-linking technology for screening the neuraminidase inhibitors from traditional Chinese medicines. The substrate and product were separated by CE in short-end injection mode within 2 min. Dual-wavelength ultraviolet detection was employed to eliminate the interference from the screened compounds. The parameters relating to the separation efficiency and the activity of immobilized neuraminidase were systematically evaluated. The activity of the immobilized neuraminidase remained 90% after 30 days storage at 4°C. The immobilized NA microreactor could be continuously used for more than 200 runs. The Michaelis-Menten constant of neuraminidase was determined by the microreactor as 136.6 ± 10.8 μM. In addition, six in eighteen natural products were found as potent inhibitors and the inhibition potentials were ranked in the following order: bavachinin>bavachin>baicalein>baicalin>chrysin and vitexin. The half-maximal inhibitory concentrations were 59.52 ± 4.12, 65.28 ± 1.07, 44.79 ± 1.21 and 31.62 ± 2.04 for baicalein, baicalin, bavachin and bavachinin, respectively. The results demonstrated that the neuraminidase-immobilized capillary microreactor was a very effective tool for screening neuraminidase inhibitors from traditional Chinese medicines.

Topics: Drugs, Chinese Herbal; Electrophoresis, Capillary; Enzyme Inhibitors; Enzymes, Immobilized; Flavanones; Flavonoids; Neuraminidase

Inhibiting interleukin-6 (IL-6) has been postulated as an effective therapy in the pathogenesis of several inflammatory diseases. In this study, seven flavonoids were isolated from the methanol extracts of Psoralea corylifolia by bioactivity-guided fractionation. The structures of bakuchiol (1), bavachinin (2), neobavaisoflavone (3), corylifol A (4), corylin (5), isobavachalcon (6), and bavachin (7) were determined by spectroscopic analysis (1H-, 13C- NMR and MS). We demonstrated that compounds 1-7 showed an inhibitory effect on IL-6-induced STAT3 promoter activity in Hep3B cells with IC50 values of 4.57 ± 0.45, 3.02 ± 0.53, 2.77 ± 0.02, 0.81 ± 0.15, 1.37 ± 0.45, 2.45 ± 0.13, and 4.89 ± 0.05 µΜ, respectively. These compounds also inhibited STAT3 phosphorylation induced by IL-6 in Hep3B cells. Overall, several flavonoids from P. corylifolia might be useful remedies for treating inflammatory diseases by inhibiting IL-6-induced STAT3 activation and phosphorylation.

Topics: Anti-Inflammatory Agents; Cell Line; Drug Evaluation, Preclinical; Flavones; Flavonoids; Humans; Inhibitory Concentration 50; Interleukin-6; Isoflavones; Molecular Structure; Phenols; Phosphorylation; Plant Extracts; Plants, Medicinal; Promoter Regions, Genetic; Psoralea; STAT3 Transcription Factor; Structure-Activity Relationship; Tyrosine

A meroterpene and four flavonoids were isolated from the seeds of Psoralea corylifolia as antioxidative components. Their structures were elucidated by spectral data and identified as bakuchiol (1), bavachinin (2), bavachin (3), isobavachin (4) and isobavachalcone (5). In particular, meroterpene 1 and flavonoids 4 and 5 showed broad antioxidative activities in rat liver microsomes and mitochondria. They inhibited NADPH-, ascorbate-, t-BuOOH- and CCl(4)-induced lipid peroxidation in microsomes. They also prevented NADH-dependent and ascorbate-induced mitochondrial lipid peroxidation. Bakuchiol (1) was the most potent antioxidant in microsomes and the inhibition of oxygen consumption induced by lipid peroxidation was time-dependent. Furthermore, bakuchiol (1) protected human red blood cells against oxidative haemolysis. These phenolic compounds in P. corylifolia were shown to be effective in protecting biological membranes against various oxidative stresses.

Topics: Animals; Antioxidants; Chalcone; Chalcones; Erythrocytes; Flavonoids; Hemolysis; Humans; Lipid Peroxidation; Male; Microsomes, Liver; Mitochondria; Molecular Structure; Oxygen Consumption; Phenols; Plant Extracts; Psoralea; Rats; Rats, Wistar; Seeds