peoniflorin and naringin

SiNiSan (SNS) is an ancient Chinese herbal prescription, and the current clinical treatment of irritable bowel syndrome (IBS) is effective. In the previous study of the research team, the multi-functional co-synergism of SNS against IBS was presented. Some potential drug targets and candidate ligands were predicted.. This study attempts to explore the crucial ingredient combinations from SNS formula and reveal their synergistic mechanism for IBS therapy.. In present study, a comprehensive strategy was performed to reveal IBS related pathways and biological modules, and explore synergistic effects of the ingredients, including ADME (absorption, distribution, metabolism, excretion) screening, Text mining, Venn analysis, Gene ontology (GO) analysis, Pathway cluster analysis, Molecular docking, Network construction and Experimental verification in visceral hypersensitivity (VHS) rats.. Three compressed IBS signal pathways were derived from ClueGO KEGG analysis of 63 IBS genes, including Neuroactive ligand-receptor interaction, Inflammatory mediator regulation of TRP (transient receptor potential) channels and Serotonergic synapse. A multi-module network, composed of four IBS therapeutic modules (psychological, inflammation, neuroendocrine and cross-talk modules), was revealed by Target-Pathway network. Nine kernel targets were considered closely associated with the IBS pathways, including ADRA2A, HTR2A, F2RL1, F2RL3, TRPV1, PKC, PKA, IL-1Β and NGF. In silico analysis revealed that three crucial ingredients (synephrine, paeoniflorin and naringin) were assumed to coordinate the network of those IBS therapeutic modules by acting on these kernel targets in the important pathways. In vivo experimental results showed that the crucial ingredient combinations synergistically affected the expressions of the kernel biological molecules, and improved the minimum capacity threshold of AWR in VHS rats.. The study proposes the important IBS associated pathways and the network regulation mechanisms of the crucial ingredients. It reveals the multi-target synergistic effect of the crucial ingredient combinations for the novel therapy on IBS.

Topics: Animals; Data Mining; Drugs, Chinese Herbal; Flavanones; Glucosides; Humans; Inflammation; Interleukin-6; Irritable Bowel Syndrome; Male; Molecular Docking Simulation; Monoterpenes; Proto-Oncogene Proteins c-raf; Rats, Sprague-Dawley; Signal Transduction; Synephrine; Transient Receptor Potential Channels

1. Si-Ni-San (SNS) possesses extensive therapeutic effects, however, the extent to which main components are absorbed and the mechanisms involved are controversial. 2. In this study, MDCK cell model was used to determine the permeability characteristics and interaction between the major components of Si-Ni-San, including saikosaponin a, paeoniflorin, naringin and glycyrrhizic acid. 3. The transport of the major components was concentration-dependent in both directions. Moreover, the transport of paeoniflorin, naringin and glycyrrhizic acid was significantly reduced at 4 °C or in the presence of NaN3. Additionally, the efflux of paeoniflorin and naringin were apparently reduced in the presence of P-gp inhibitor verapamil. The transport of glycyrrhizic acid was clearly inhibited by the inhibitors of MRP2, indicating that MRP2 may be involved in the transport of glycyrrhizic acid. However, the results indicated that saikosaponin a was absorbed mainly by passive diffusion. Furthermore, the combined incubation of four major components had a powerful sorbefacient effect than a single drug used alone which may be regulated by tight junctions. 4. Taken together, our study provides useful information for pharmacological applications of Si-Ni-San and offers new insights into this ancient decoction for further researches, especially in drug synergism.

Topics: Animals; Biological Transport; Dogs; Drugs, Chinese Herbal; Flavanones; Glucosides; Glycyrrhizic Acid; Humans; Madin Darby Canine Kidney Cells; Models, Biological; Monoterpenes; Oleanolic Acid; Permeability; Saponins; Verapamil

The selection of quality control indicators in a complex system is a key scientific issue for the study of Chinese materia medica (CMM), which is directly related to its safety and efficacy. In order to scientifically understand and control the quality of CMM, quality marker (Q-marker) has been recently raised as a new concept, which provided a novel research idea for the quality control and evaluation of CMM.. By a new and integrated "spider-web" mode, Q-markers of Xuefu Zhuyu capsule (XZC) were comprehensively uncovered, conducing to great improvement of quality control of XZC.. Mainly established by three dimensions derived from six variables including content, stability and activity, "spider-web" mode was constructed to evaluate Q-marker property of candidate compounds by taking regression area of the tested compounds into account.. The candidate compounds with larger regression area were preferentially adopted as Q-markers, which should possess the satisfactorily integrated properties of content, stability and activity. Six compounds, naringin, isoliquiritin, paeoniflorin, protocatechuic acid, neohesperidin and ferulic acid, were identified and preferred as Q-markers of XZC.. Based on "spider-web" mode, Q-markers from Xuefu Zhuyu capsule were successfully screened, which would substantially perform quality control of XZC and prove the feasibility of "spider-web" mode in solving the selection of quality control indicators from compound formulae.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers, Pharmacological; Capsules; Chalcone; Coumaric Acids; Drug Stability; Drugs, Chinese Herbal; Flavanones; Glucosides; Hesperidin; Hydroxybenzoates; Materia Medica; Mice; Monoterpenes; Quality Control; RAW 264.7 Cells

SiNiSan (SNS) is a traditional Chinese medicine (TCM) prescription that has been widely used in the clinical treatment of irritable bowel syndrome (IBS). However, the underlying active substances and molecular mechanisms remain obscure.. A bioinformatics/topology based strategy was proposed for identification of the drug targets, therapeutic agents and molecular mechanisms of SiNiSan against irritable bowel syndrome.. In this work, a bioinformatics/network topology based strategy was employed by integrating ADME filtering, text mining, bioinformatics, network topology, Venn analysis and molecular docking to uncover systematically the multicomponent synergy mechanisms. In vivo experimental validation was executed in a Visceral Hypersensitivity (VHS) rat model.. 76 protein targets and 109 active components of SNS were identified. Bioinformatics analysis revealed that 116 disease pathways associated with IBS therapy could be classified into the 19 statistically enriched functional sub-groups. The multi-functional co-synergism of SNS against IBS were predicted, including inflammatory reaction regulation, oxidative-stress depression regulation and hormone and immune regulation. The multi-component synergetic effects were also revealed on the herbal combination of SNS. The hub-bottleneck genes of the protein networks including PTGS2, CALM2, NOS2, SLC6A3 and MAOB, MAOA, CREB1 could become potential drug targets and Paeoniflorin, Naringin, Glycyrrhizic acid may be candidate agents. Experimental results showed that the potential mechanisms of SiNiSan treatment involved in the suppression of activation of Dopaminergic synapse and Amphetamine addiction signaling pathways, which are congruent with the prediction by the systematic approach.. The integrative investigation based on bioinformatics/network topology strategy may elaborate the multicomponent synergy mechanisms of SNS against IBS and provide the way out to develop new combination medicines for IBS.

Topics: Animals; Computational Biology; Data Mining; Disease Models, Animal; Drug Evaluation, Preclinical; Drug Synergism; Drugs, Chinese Herbal; Flavanones; Glucosides; Humans; Irritable Bowel Syndrome; Male; Medicine, Chinese Traditional; Molecular Docking Simulation; Monoterpenes; Protein Interaction Maps; Proteins; Rats, Sprague-Dawley; Signal Transduction

Topics: Animals; Buffers; Cell Line; Electricity; Electrophoresis, Capillary; Flavanones; Glucosides; Iridoid Glucosides; Iridoids; Macrophages; Mice; Monoterpenes

The pharmacokinetic differences of paeoniflorin, naringin, naringenin and glycyrrhetinic acid (GA) following oral administration of pure compounds, single herbs and Si-Ni-San (SNS) decoction to rats were studied. Blood samples were analyzed with a validated UPLC-MS/MS method. Student's t-test was used for the statistical comparison. The Cmax and AUC0-∞ were 1470±434 ng/mL and 4663±916 ng h/mL for paeoniflorin, 64.29±59.21 ng/mL and 311.8±131.8 ng h/mL for naringin, 244.2±138.8 ng/mL and 4761±3167 ng h/mL for naringenin, and 1183±294 ng/mL and 38 994±14 377 ng h/mL for GA after oral administration of paeoniflorin, naringin and glycyrrhizic acid. The Cmax and AUC0-∞ were 812.6±259.6 ng/mL and 2489±817 ng h/mL for paeoniflorin, 344.3±234.9 ng/mL and 1479±531 ng h/mL for naringin, 981.9±465.4 ng/mL and 12 284±6378 ng h/mL for naringenin, and 3164±742 ng/mL and 78 817±16 707 ng h/mL for GA after oral administration of SNS decoction. There were significant differences between the pharmacokinetic behavior after oral administration of SNS decoction compared with pure components or herbs. The results indicated that some components in the other herbs of SNS had a pharmacokinetic interaction with paeoniflorin, naringin, naringenin and GA.

Topics: Administration, Oral; Animals; Drugs, Chinese Herbal; Flavanones; Glucosides; Glycyrrhetinic Acid; Male; Monoterpenes; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

A UPLC-MS/MS method was developed for the simultaneous determination of paeoniflorin, naringin, naringenin and glycyrrhetinic acid in rat plasma. A Waters BEH C(18) column was used with a gradient mobile phase system of methanol-water containing 2 mM ammonium acetate. The analysis was performed on a positive ionization electrospray mass spectrometer via multiple reaction monitoring (MRM). One-step protein precipitation with acetonitrile was used to extract the analytes from plasma. The limits of quantification were 9.800 ng/ml for paeoniflorin, 5.100 ng/ml for naringin, 5.200 ng/ml for naringenin and 10.60 ng/ml for glycyrrhetinic acid, respectively. The intra- and inter-day precision (relative standard deviation, RSD) ranged 4.9-12% and 2.8-13%, respectively. The accuracy (relative error, RE) was from -7.3% to 7.5% at all quality control (QC) levels. The validated method was applied to a pharmacokinetic study in rats after oral administration of Si-Ni-San decoction.

Topics: Administration, Oral; Animals; Benzoates; Bridged-Ring Compounds; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Flavanones; Glucosides; Glycyrrhetinic Acid; Limit of Detection; Male; Monoterpenes; Quality Control; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

To study the anti-inflammatory effects of the combinations of active components of Painong powder, a compound traditional Chinese herbal medicine, and the quantitative analysis of their interactions.. The mouse model of acute inflammation with increase of capillary permeability was induced by intraperitoneal injection of acetic acid. An orthogonal design with 2 levels (used and unused) was applied to assign the combinations groups of active ingredients including naringin and neohesperidin, peoniflorin, and platycodin. Aspirin and normal saline were administered as control. The pharmacodynamic interactions were analyzed by the optical density (OD) of infiltrated Evans blue.. The different combinations of active ingredients showed anti-inflammatory effect with different degree, and the predicted values of OD varied from 0.115 to 0.170. The maximum anti-inflammatory effect was from the combination of naringin, neohesperidin, paeoniflorin and platycodin, better than that of the saline group (P < 0.01). However, there was no significant difference as compared with the aspirin group (P > 0.05). Paeoniflorin showed a dominant contribution to the formula, and platycodin the least. The combination of all active components exhibited synergism.. The results suggest that all the ingredients are efficacious constituents of the formula, and paeoniflorin shows a dominant contribution to the formula. More information about prescription compatibility can be obtained by the orthogonal simulation method.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Benzoates; Bridged-Ring Compounds; Drug Evaluation, Preclinical; Drug Synergism; Drugs, Chinese Herbal; Female; Flavanones; Glucosides; Hesperidin; Male; Mice; Monoterpenes; Powders; Saponins

An HPLC-photodiode array (PDA) detection method was established for the simultaneous determination of 12 components in Xiao-Yao-San-Jia-Wei (XYSJW): geniposide, puerarin, paeoniflorin, ferulic acid, liquiritin, hesperidin, naringin, paeonol, daidzein, glycyrrhizic acid, honokiol, and magnolol. These were separated in less than 70 min using a Waters Symmetry Shield RP 18 column with gradient elution using (A) acetonitrile, (B) water, and (C) acetic acid at a flow rate of 1 ml/min, and with a PDA detector. All calibration curves showed good linear regression (r(2)>0.9992) within the test ranges. The method was validated for specificity, accuracy, precision, and limits of detection. The proposed method enables in a single run the simultaneous identification and determination for quality control of 12 multi-structural components of XYSJW forming the basis of its therapeutic effect.

Topics: Acetophenones; Benzoates; Biphenyl Compounds; Bridged-Ring Compounds; Coumaric Acids; Drugs, Chinese Herbal; Flavanones; Glucosides; Glycyrrhizic Acid; Hesperidin; Iridoids; Isoflavones; Lignans; Medicine, Chinese Traditional; Molecular Structure; Monoterpenes; Quality Control; Reference Standards; Reproducibility of Results; Sensitivity and Specificity

Previously, we demonstrated the inhibitory effects of Si-Ni-San, a traditional Chinese prescription, on picryl chloride-induced ear contact sensitivity (PCl-CS). This study aimed to evaluate the role of the four major constituents contained in the prescription (saikosaponins, paeoniflorin, naringin and glycyrrhizin) in the inhibitory effect. When administered during the induction phase, saikosaponin a and glycyrrhizin showed significant inhibitory effects, while paeoniflorin and naringin did not. These components in Si-Ni-San also inhibited the activation and proliferation of T lymphocytes as well as the production of cytokines such as tumour necrosis factor-alpha and interferon-gamma to different extents. Saikosaponin a and paeoniflorin dose-dependently reduced the splenocyte adhesion to type I collagen, while glycyrrhizin only showed a slight tendency. Furthermore, treatment with glycyrrhizin or saikosaponin a, rather than paeoniflorin or naringin, moderately inhibited the matrix metalloproteinase (MMP)-2 activity of the splenocytes from PCl-CS mice, and the combination of all four components showed a strong inhibition against MMP-2. Moreover, the components markedly decreased the serum level of nitric oxide in PCl-sensitized mice. The results indicated that saikosaponin a and glycyrrhizin may be the major contributors in the alleviation effect of Si-Ni-San on contact sensitivity, and paeoniflorin and naringin may exhibit a co-operative effect.

Topics: Animals; Benzoates; Bridged-Ring Compounds; Cell Adhesion; Cells, Cultured; Concanavalin A; Dermatitis, Allergic Contact; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Female; Flavanones; Glucosides; Glycyrrhizic Acid; Immunosuppressive Agents; Interferon-gamma; Lymphocyte Activation; Lymphocytes; Matrix Metalloproteinase 2; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Monoterpenes; Nitric Oxide; Oleanolic Acid; Picryl Chloride; RNA, Messenger; Saponins; Spleen

To develop a method for quality control of effective fraction in Qi-Xue-Bing-Zhi decoction, a traditional Chinese medicine (TCM).. PF samples, effective fraction from Qi-Xue-Bing-Zhi decoction, were used as example, and a HPLC assay for chemical fingerprint and quantitative analysis was established.. The contents range of Paeoniflorin (PE), Naringin (NG) and Neohesperidin (NH) in effective fractions were changed from 12.5%-16.0%, 8.4%-12.4%, 12.8%-15.3%, and their average contents were (14.7 +/- 1.1)%, (10.6 +/- 1.2)%, (14.2 +/- 0.8)% (n = 10), respectively. The fingerprints of PF samples showed 25 common peaks, and the fingerprint similarity for PF samples were all above 99.00% by comparing with the standard chromatogram.. The method reported could be used effectively for the quality control of effective fraction from TCM.

Topics: Benzoates; Bridged-Ring Compounds; Chromatography, High Pressure Liquid; Drug Combinations; Drugs, Chinese Herbal; Flavanones; Glucosides; Hesperidin; Ligusticum; Monoterpenes; Paeonia; Plants, Medicinal; Quality Control; Reproducibility of Results