neoisoliquiritin and liquiritigenin

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

Screening active constituents of traditional Chinese medicines (TCMs) is vital for lead compound discovery. Sini decoction (SND) is a well-known TCM formula for relieving myocardial ischemia (MI) in clinic. Due to complex nature, the effective compounds of SND are still unknown. In this study, a novel "system to system" strategy based on the correlation of drug-related and drug-induced ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOFMS) serum metabolomic profiles was developed to discover bioactive compounds of SND against isoproterenol-induced MI. Thirteen SND-induced metabolites and 19 SND-related metabolites were identified by UHPLC-Q-TOFMS coupled with S-plot and SUS-plot of orthogonal projection to latent structure-discriminant analysis (OPLS-DA) models, respectively. Canonical correlation analysis between the SND-induced and SND-related metabolites revealed that 12 compounds had strongly correlated relationship with the protective effect of SND on MI, and these compounds include isotalatizidine, songorine, fuziline, neoline, talatizamine, 14-acetyltalatizamine, liquiritigenin, benzoylmesaconitine, isoliquiritin, benzoylaconitne, benzoylhypaconitine and 6-gingerol. Combination functional enrichment analysis and network topology analysis revealed that the targeted metabolic pathways of these correlated compounds were involved in valine, leucine and isoleucine biosyntheses, tryptophan metabolism, glycerophospholipid metabolism and sphingolipid metabolism. The results demonstrated that the "system to system" strategy may be a high-throughput method to discover potentially effective compounds from TCMs.

Topics: Aconitine; Alkaloids; Animals; Aspartate Aminotransferases; Catechols; Chalcone; Chromatography, High Pressure Liquid; Creatine Kinase; Disease Models, Animal; Drugs, Chinese Herbal; Fatty Alcohols; Flavanones; Glucosides; L-Lactate Dehydrogenase; Lipid Peroxidation; Male; Malondialdehyde; Mass Spectrometry; Metabolome; Myocardial Ischemia; Rats; Rats, Sprague-Dawley; Superoxide Dismutase

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

Topics: Administration, Oral; Animals; Chalcone; Chromatography, High Pressure Liquid; Cinnamates; Drugs, Chinese Herbal; Flavanones; Glucosides; Glycyrrhetinic Acid; Glycyrrhizic Acid; Male; Plasma; Rats; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry

Liquiritigenin (LQG), isoliquiritin (ILQ) and isoliquiritigenin (ILG) are flavonoids derived from liquorice and all possess a similar chemical structural backbone. In the current study, we found that ILQ and ILG had suppressive effects on lipopolysaccharide (LPS)-induced inflammatory responses in murine macrophage by suppressing the iNOS and COX-2 proteins and mRNA expression. A mechanistic study indicated that the effect was associated with an induction of antioxidant and detoxification enzymes, including UGT1A1, NQO1, and heme oxygenase-1 (HO-1) mRNA expression. The regulator of these enzymes, nuclear factor-erythroid 2-related factor 2 (Nrf2), which plays a critical role in LPS-induced inflammatory responses, could be activated by ILQ and ILG. Additionally, ILQ and ILG promoted Nrf2 signaling activation by inhibiting the Kelch-like ECH-associated protein 1 (Keap1) and increasing Nrf2 translocation, inducing the expression of these antioxidant enzymes. We further found that ILQ and ILG induced HO-1 expression independent of Nrf2 expression. With respect to the effect of these compounds on NF-κB signaling, ILG was found to markedly inhibit IκBα degradation and phosphorylation, while LQG and ILQ had no significant effects. These results indicate that there are correlations between the anti-inflammatory responses and the chemical structural properties of these flavonoids.

Topics: Animals; Anti-Inflammatory Agents; Cell Line; Chalcone; Chalcones; Cyclooxygenase 2; Flavanones; Glucosides; Glycyrrhiza; HEK293 Cells; Heme Oxygenase-1; Hep G2 Cells; Humans; Lipopolysaccharides; Macrophage Activation; Mice; NF-E2-Related Factor 2; Nitric Oxide Synthase Type II; RNA, Messenger; Up-Regulation

A complex formula composed of Paeonia lactiflora PALL. and Glycyrrhiza uralensis Fisch., which is called as Jakyak-Gamcho Decoction (JGD), has been used for a pain-relieving function and muscle spasms due to blood deficiency in the traditional medicine. In this study, the anti-inflammatory activity of JGD was evaluated based on the quantitative determinations and the relative proportions of six major constituents in the decoction mixture extracted by orthogonal array methods. Our results suggest that the three parameters are all crucial factors. The optimized conditions for extraction were therefore established [solvent (water); pH value (4); extraction number (4)]. We also optimized the extraction conditions related to anti-inflammatory activity [solvent (70% EtOH); pH value (6); extraction number (4)]. So, we found that the bioactivity was responsible for mixed components but not individual one. It was proportionally associated with the amounts of some components in the extracts of herbal medicines. When the proportion of the active components was similar to each other, they had the similar functions. Furthermore, the results could establish a model system for the quality assurance of herbal preparations, and provided a new paradigm of active components-pharmacodynamics, which is used for illustrating the connections between the bioactivities and the proportion of active constituents in the extracts of herbal medicines.

Topics: Alkaline Phosphatase; Animals; Benzoates; Bridged-Ring Compounds; Cell Line; Cell Survival; Chalcone; Chemical Fractionation; Chromatography, High Pressure Liquid; Ethanol; Flavanones; Glucosides; Glycyrrhiza; Glycyrrhizic Acid; Herbal Medicine; Lipopolysaccharides; Macrophages; Monoterpenes; NF-kappa B; Nitric Oxide; Paeonia; Plant Extracts; Research Design; Solubility; Technology, Pharmaceutical; Water