corylifol-a and bavachin

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

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

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