likviriton and neoisoliquiritin

Huangqi decoction (HQD) has been used to treat chronic liver diseases since the 11th century, but the effective components in HQD against liver fibrosis have not been definitively clarified.. To investigate and identify multiple effective components in HQD against liver fibrosis using a pharmacokinetics-based comprehensive strategy.. The absorbed representative components in HQD and their metabolites were detected in human plasma and urine using high-resolution mass spectrometry combined with a database-directed method, and then pharmacokinetics in multiple HQD components in human plasma was analyzed by ultra-performance liquid chromatography coupled with triple-quadruple mass spectrometry. Furthermore, the anti-fibrotic effect of potential effective HQD components was studied in LX-2 cells and that of a multi-component combination of HQD (MCHD) was verified in a mouse CCl. Twenty-four prototype components in HQD and 17 metabolites were identified in humans, and the pharmacokinetic characteristics of 14 components were elucidated. Among these components, astragaloside IV, cycloastragenol, glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin, and isoliquiritigenin downregulated the mRNA expression of α-SMA; cycloastragenol, calycosin-7-O-β-D-glucoside, formononetin, glycyrrhetinic acid, liquiritin, and isoliquiritin downregulated the mRNA expression of Col I; and calycosin, liquiritigenin, isoliquiritigenin, cycloastragenol, and glycyrrhetinic accelerated the apoptosis of LX-2 cells. MCHD reduced serum aminotransferase activity and hepatic collagen fibril deposition in mice with CCl. Using the pharmacokinetics-based comprehensive strategy, we revealed that multiple effective HQD components act together against liver fibrosis.

Topics: Adolescent; Adult; Animals; Chalcone; Chromatography, Liquid; Drugs, Chinese Herbal; Flavanones; Glucosides; Glycyrrhizic Acid; Humans; Liver Cirrhosis; Male; Mass Spectrometry; Mice, Inbred C57BL; Middle Aged; Saponins; Triterpenes; Young Adult

Previously, we have investigated the therapeutic mechanism of Qingzao Jiufei Decoction (QZJFD), a Chinese classic prescription, on acute lung injury (ALI), however, which remained to be further clarified together with the underlying efficacy related compounds for quality markers (Q-markers).. To explore Q-markers of QZJFD on ALI by integrating a stepwise multi-system with 'network pharmacology-metabolomics- pharmacokinetic (PK)/ pharmacodynamic (PD) modeling'.. First, based on in vitro and in vivo component analysis, a network pharmacology strategy was developed to identify active components and potential action mechanism of QZJFD on ALI. Next, studies of poly-pharmacology and non-targeted metabolomics were used to elaborate efficacy and verify network pharmacology results. Then, a comparative PK study on active components in network pharmacology was developed to profile their dynamic laws in vivo under ALI, suggesting Q-marker candidates. Next, quantified analytes with marked PK variations after modeling were fitted with characteristic endogenous metabolites along drug concentration-efficacy-time curve in a PK-PD modeling to verify and select primary effective compounds. Finally, Q-markers were further chosen based on representativeness among analytes through validity analysis of PK quantitation of primary effective compounds.. In virtue of 121 and 33 compounds identified in vitro and in vivo, respectively, 33 absorbed prototype compounds were selected to construct a ternary network of '20 components-47 targets-113 pathways' related to anti-ALI of QZJFD. Predicted mechanism (leukocytes infiltration, cytokines, endogenous metabolism) were successively verified by poly-pharmacology and metabolomics. Next, 18 measurable components were retained from 20 analytes by PK comparison under ALI. Then, 15 primary effective compounds from 18 PK markers were further selected by PK-PD analysis. Finally, 9 representative Q-markers from 15 primary effective compounds attributed to principal (chlorogenic acid), ministerial (methylophiopogonanone A, methylophiopogonanone B), adjuvant (sesamin, ursolic acid, amygdalin), conductant drugs (liquiritin apioside, liquiritigenin and isoliquiritin) in QZJFD, were recognized by substitutability and relevance of plasmatic concentration at various time points.. 9 Q-markers for QZJFD on ALI were identified by a stepwise integration strategy, moreover, which was a powerful tool for screening Q-makers involved with the therapeutic action of traditional Chinese medicine (TCM) prescription and promoting the process of TCM modernization and scientification.

Topics: Acute Lung Injury; Administration, Oral; Amygdalin; Animals; Biological Availability; Biomarkers, Pharmacological; Chalcone; Chlorogenic Acid; Dioxoles; Drugs, Chinese Herbal; Flavanones; Glucosides; Lignans; Male; Metabolomics; Rats, Wistar; Triterpenes; Ursolic Acid

Jiegeng Gancao decoction, which is composed of Jiegeng and Gancao at a weight ratio of 1:2, was widely used for treating pharyngalgia and cough for thousands of years. Our previous work indicated that Gancao could increase the systemic exposure of platycodin D and deapio-platycodin D, two main components in Jiegeng. However, whether Jiegeng could alter the pharmacokinetics of the main compounds in Gancao is still unknown. Thus, the purpose of this study was to compare the oral pharmacokinetics of flavonoids and saponins from Gancao alone vs. after co-administration with Jiegeng. Furthermore, Caco-2 cell transport and fecal hydrolysis were investigated to explain the altered pharmacokinetic properties. Pharmacokinetics results suggested that the bioavailability of liquiritin, isoliquiritin, glycyrrhizin and its metabolite, glycyrrhetinic acid, could be improved while bioavailability of liquiritigenin and isoliquiritigenin deteriorated when co-administered with Jiegeng. The Caco-2 transport study showed no significant difference of the P

Topics: Caco-2 Cells; Chalcone; Flavanones; Flavonoids; Glucosides; Glycyrrhiza uralensis; Humans; Saponins; Triterpenes

Licorice is one of the most common herbs in traditional Chinese medicine, and classified as top\ grade in Shen Nong Ben Cao Jing. There are three different original plants of licorice stipulated in Chinese\ Pharmacopeia, Glycyrrhiza uralensis Fisch., Glycyrrhiza glabra L., and Glycyrrhiza inflata Bat. However,\ previous investigation showed that the pharmacodynamic effects of the three licorices were quite different. It is\ very difficult to identify them by the classical identification methods. In order to establish a fast and effective\ identification method, we collected 240 licorice plants from 21 populations of 7 provinces, and amplified their\ ITS and psbA-trnH sequences. ITS sequences with a full length of 616 bp and psbA-trnH sequences with a full\ length of 389 bp were obtained separately. Using DNAMAN to analyze these sequences, 4 variable sites were\ found in ITS sequences and 2 ITS haplotypes were determined, and 3 variable sites were found in psbA-trnH\ sequences and 4 psbA-trnH haplotypes were determined. With the combination analysis of ITS and psbA-trnH\ sequences, the molecular identification method of original licorice was established. Using this method, 40\ samples of licorice slices collected from 4 main herbal material markets in China were identified successfully.\ Furthermore, the contents of 2 triterpenes, 18α-glycyrrhizic acid and 18β-glycyrrhizic acid, and 4 flavonoids,\ liquiritin, isoliquiritin, liquiritigenin, and isoliquiritigenin in these licorice pieces were examined by HPLC and\ the results were analyzed using SPSS 21.0. This study provides a new method in identification of licorice,\ which may serve as a guideline for quality control of licorice slices.

Topics: Chalcone; Chalcones; China; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Flavanones; Flavonoids; Glucosides; Glycyrrhiza; Glycyrrhiza uralensis; Glycyrrhizic Acid; Triterpenes

Liquiritin, isoliquiritin and isoliquirigenin are the active polyphenols present in Glycyrrhiza uralensis which has been used for the treatment of cancer and its complications. The present study was conducted to evaluate the cytotoxicity and antitumor activity of liquiritin, isoliquiritin and isoliquirigenin on human non-small lung cancer cells including apoptosis-induction, inhibition of apoptotic pathways and to explore the underlying mechanism. Lactate dehydrogenase assays, FITC Annexin V staining assay were performed to evaluate cellular cytotoxicity and apoptosis activity. The results showed that pretreatment with these polyphenols induced apoptosis in A549 cells. Liquiritin, isoliquiritin and isoliquirigenin significantly increased cytotoxicity of, and upregulated p53 and p21 and downregulated the apoptotic pathways. Furthermore, it inhibited cell cycle at the G2/M phase. Western blot analysis showed it significantly decreased the protein expression of PCNA, MDM2, p-GSK-3β, p-Akt, p-c-Raf, p-PTEN, caspase-3, pro-caspase-8, pro-caspase-9 and PARP, Bcl-2 in a concentration-dependent manner while the protein expression of p53, p21 and Bax was increased. In addition, Akt pathway was downregulated. These findings suggest that liquiritin, isoliquiritin and isoliquirigenin inhibited the p53-dependent pathway and showed crosstalk between Akt activities. These active polyphenols can be an alternative agent for the treatment of lung cancer.

Topics: Aldehyde Reductase; Apoptosis; Carcinoma, Non-Small-Cell Lung; Caspase 3; Caspase 7; Cell Line, Tumor; Cell Survival; Chalcone; Chalcones; Cyclin-Dependent Kinase Inhibitor p21; Enzyme Activation; Enzyme Inhibitors; Flavanones; Glucosides; Glycyrrhiza uralensis; Humans; L-Lactate Dehydrogenase; Lung Neoplasms; M Phase Cell Cycle Checkpoints; Plant Extracts; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Tumor Suppressor Protein p53

A rapid, highly sensitive, and selective method was applied in a non-invasive way to investigate the antidepressant action of Xiaoyaosan (XYS) using ultra performance liquid chromatography-mass spectrometry (UPLC-MS) and chemometrics. Many significantly altered metabolites were used to explain the mechanism. Venlafaxine HCl and fluoxetine HCl were used as chemical positive control drugs with a relatively clear mechanism of action to evaluate the efficiency and to predict the mechanism of action of XYS. Urine obtained from rats subjected to chronic unpredictable mild stress (CUMS) was analyzed by UPLC-MS. Distinct changes in the pattern of metabolites in the rat urine after CUMS production and drug intervention were observed using partial least squares-discriminant analysis. The results of behavioral tests and multivariate analysis showed that CUMS was successfully reproduced, and a moderate-dose XYS produced significant therapeutic effects in the rodent model, equivalent to those of the positive control drugs, venlafaxine HCl and fluoxetine HCl. Metabolites with significant changes induced by CUMS were identified, and 17 biomarker candidates for stress and drug intervention were identified. The therapeutic effect of XYS on depression may involve regulation of the dysfunctions of energy metabolism, amino acid metabolism, and gut microflora changes. Metabonomic methods are valuable tools for measuring efficacy and mechanisms of action in the study of traditional Chinese medicines.

Topics: Animals; Antidepressive Agents; Benzoates; Biomarkers; Bridged-Ring Compounds; Catechin; Chalcone; Chromatography, Liquid; Citric Acid; Citric Acid Cycle; Coumaric Acids; Creatine Kinase; Creatinine; Cyclohexanols; Drugs, Chinese Herbal; Flavanones; Fluoxetine; Gallic Acid; Gastrointestinal Tract; Glucosides; Glycine; Hippurates; Ketoglutaric Acids; Kynurenic Acid; Male; Mass Spectrometry; Metabolic Networks and Pathways; Metabolomics; Microbiota; Monoterpenes; Phytotherapy; Plant Extracts; Rats; Rats, Sprague-Dawley; Stress, Psychological; Tryptophan; Tyrosine; Venlafaxine Hydrochloride

A high performance liquid chromatographic (HPLC) method with diode array detection (DAD) was established for simultaneous determination of seven main bioactive components in San-ao decoction and its series of formulae (San-ao decoction, Wu-ao decoction, Qi-ao decoction and Jia-wei San-ao decoction). Seven compounds were analyzed simultaneously with a XTerra C(18) column (4.6 mm × 250 mm, 5 µm) using a linear gradient elution of a mobile phase containing acetonitrile (A) and a buffer solution (0.02 mol/L potassium dihydrogen phosphate and adjusted to pH 3 using phosphoric acid) (B); the flow rate was 1.0 mL/min. The sample was detected with DAD at 210, 254 and 360 nm and the column was maintained at 30 °C. All the compounds showed good linearity (r2 > 0.9984) in the tested concentration range. The precisions were evaluated by intra-day and inter-day tests, and relative standard deviation (R.S.D.) values within the range of 0.83%–2.53% and 0.64%–2.77% were reported, respectively. The recoveries of the quantified compounds were observed to cover a range from 95.34% and 104.82% with R.S.D. values less than 2.72%. The validated method was successfully applied for the simultaneous determination of seven main bioactive components including ephedrine (1), amygdalin (2), liquiritin (3), benzoic acid (4), isoliquiritin (5), formononetin (6) and glycyrrhizic acid (7) in San-ao decoction and its series of formulae. The results also showed a wide variation in the content of the identified active compounds in these samples, which could also be helpful to illustrate the drug interactions after some herbs combined in different formulations.

Topics: Amygdalin; Benzoic Acid; Calibration; Chalcone; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Ephedrine; Flavanones; Glucosides; Glycyrrhizic Acid; Isoflavones; Limit of Detection; Medicine, Chinese Traditional; Reference Standards; Signal-To-Noise Ratio; Spectrophotometry, Ultraviolet

Two classic animal behavior despair tests--the Forced Swimming Test (FST) and the Tail Suspension Test (TST) were used to evaluate the antidepressant activity of liquiritin and isoliquiritin from Glycyrrhiza uralensis in mice. It was observed that both liquiritin and isoliquiritin at doses of 10, 20 and 40 mg/kg significantly reduced the immobility time in the FST and TST in mice 30 min after treatment. Measurement of locomotor activity indicated that liquiritin and isoliquiritin had no central nervous system (CNS)-stimulating effects. The main monoamine neurotransmitters and their metabolites in mouse brain regions were also simultaneously determined by HPLC-ECD. It was found that these two compounds significantly increased the concentrations of the main neurotransmitters 5-HT and NE in the hippocampus, hypothalamus and cortex. Liquiritin and isoliquiritin also significantly reduced the ratio of 5-HIAA/5-HT in the hippocampus, hypothalamus and cortex, slowing down 5-HT metabolism compared with mice treated with vehicle+stress. In conclusion, liquiritin and isoliquiritin produced significant antidepressant-like effects, and their mechanism of action may be due to increased 5-HT and NE in the mouse hippocampus, hypothalamus and cortex.

Topics: Analysis of Variance; Animals; Antidepressive Agents; Behavior, Animal; Brain Chemistry; Chalcone; Dose-Response Relationship, Drug; Flavanones; Glucosides; Glycyrrhiza uralensis; Hindlimb Suspension; Immobility Response, Tonic; Mice; Motor Activity; Neurotransmitter Agents; Swimming

Liquiritin was extracted from the natural product Licorice, and then purified using a three-zone simulated moving bed set up in our laboratory, with a C(18)-bonded silica as the stationary phase and an aqueous solution of ethanol as the mobile phase. The isotherm parameters of Liquiritin and of the only closely eluting impurity were obtained using the inverse method, fitting the experimental elution profiles to calculated elution profiles, assuming a binary Langmuir isotherm model as an approximation. The operating parameters of the simulated moving bed were selected according to the Equilibrium Theory. This allowed the preparation of 85% pure Liquiritin. Finally, 99% pure Liquiritin was obtained through a last step of recrystallization.

Topics: Algorithms; Chalcone; Chromatography; Computer Simulation; Ethanol; Flavanones; Glucosides; Isomerism; Models, Theoretical; Molecular Structure; Reproducibility of Results; Silicon Dioxide; Thermodynamics

Selective adsorption of active ingredients liquiritin and isoliquiritin from Glycyrrhiza uralensis Fisch with multi-walled carbon nanotubes (MWNTs) has been studied. Distribution coefficients of liquiritin between ethanol solvent and r-MWNTs or o-MWNTs in 293K is 37.5 and 43.3, while the distribution coefficients of isoliquiritin between ethanol solvent and r-MWNTs or o-MWNTs is 717 and 1080, respectively. It was indicated that the distribution coefficient of isoliquiritin adsorbed by MWNTs was much larger than that of liquiritin, and oxidation treatment of MWNTs could obviously enhance their adsorption ability. The possible reasons that MWNTs can selectively adsorb isoliquiritin other than liquiritin were discussed on the bases of molecular structure of the active ingredients and their interaction with nanotubes.

Topics: Adsorption; Chalcone; Flavanones; Glucosides; Glycyrrhiza uralensis; Nanotubes, Carbon; Plants, Medicinal