nuezhenide and rhodioloside

A phenyl ethanoid, salidroside (SAL), and two secoiridoids, 8(

Topics: Fibrosarcoma; Fruit; Glucosides; Humans; Ligustrum; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Phenols; Pyrans; Tetradecanoylphorbol Acetate

Er-Zhi-Wan (EZW) is a traditional Chinese medicine with many clinical applications and used as a health product in East Asia. Five active ingredients (salidroside, specnuezhenide, nuezhenoside, luteolin, and oleanolic acid) were screened out from EZW to develop an in vitro rapid evaluation method for the classification of in vivo drug absorption behavior by biopharmaceutics classification system (BCS). Ultra-performance liquid chromatography was used for quantitative analysis. Solubility and permeability were assayed by equilibrium solubility and multiple models: everted rat intestinal sac model, cultured Caco-2 cells, octanol-water partition coefficient (LogP) method. The BCS properties of drugs were predicted using software applications, and the correlations of measured and predicted values of factors affecting oral drug absorption were calculated. The results were verified by measuring the absolute bioavailability of the active ingredients. Salidroside, specnuezhenide, and nuezhenoside were classified as BCS class III drugs, and luteolin was classified as a BCS class III/I drug because of the difference in LogP and intestinal permeability. Oleanolic acid was classified as a BCS class II/IV drug in acidic media and BCS class I/III drug in other media. Overall, EZW may be classified as a BCS class III drug, and permeability was identified as the primary factor limiting absorption. The results provide a novel method for the evaluation of the in vivo absorption of oral traditional Chinese medicines.

Topics: Animals; Biological Availability; Caco-2 Cells; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Glucosides; Humans; Intestinal Absorption; Limit of Detection; Linear Models; Luteolin; Male; Oleanolic Acid; Permeability; Phenols; Pyrans; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Software; Solubility

The aim of this study was to establish and validate a rapid and sensitive LC-MS/MS method for the simultaneous determination of specnuezhenide and its bioactive metabolite salidroside in rat plasma. Protein precipitation was carried out and the analytes were separated on a Waters Acquity UPLC HSS T3 column (2.1 × 100 mm, 1.8 μm). A mobile phase consisting of acetonitrile and 0.1% formic acid aqueous solution was used for elution under gradient conditions at a flow rate of 0.4 mL/min. Quantification was performed in the negative multiple reaction monitoring mode with precursor-to-product transitions at m/z 685.2 → 453.1 for specnuezhenide, m/z 229.3 → 119.0 for salidroside and 493.2 → 147.1 for the internal standard. The method showed good linearity, accuracy, precision and stability in the range 0.5-500.0 ng/mL for specnuezhenide and salidroside. The values of the matrix effect were within the range of 100.02-111.87% for both analytes, while the mean extraction recovery was within the range 64.19-78.26%. The intra- and inter-day precisions (RSD) were <13.49% and the accuracy (RR) ranged from 93.59 to 102.24%. This study was successfully utilized for the pharmacokinetic study of specnuezhenide in rats after oral and intravenous administration. The oral bioavailability of specnuezhenide was 1.93%.

Topics: Animals; Chromatography, Liquid; Glucosides; Linear Models; Male; Phenols; Pyrans; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry

The quantitative analysis of multiple indexes remains an important quality evaluation method of traditional Chinese medicine (TCM) herbal formulas. The Chinese Pharmacopoeia 2015 only stipulates the content of a single component, specnuezhenide, in Erzhiwan composed of the Fructus Ligustri Lucidi (FLL) powder and aqueous extracts of Herba Ecliptae (HE). To generalize the intrinsic quality of Erzhiwan, a novel C

Topics: Antioxidants; Apigenin; Chromatography, High Pressure Liquid; Coumarins; Drugs, Chinese Herbal; Fruit; Glucosides; Glycosides; Isomerism; Ligustrum; Limit of Detection; Oleanolic Acid; Phenols; Pyrans; Reproducibility of Results; Triterpenes; Ursolic Acid

Characteristic chromatogram of Ligustri Lucidi Fructus which were processed by heat treatment with different temperatures and times was developed by HPLC. DPPH, ABTS and FRAP assays were performed to determine the antioxidant activity. The spectrum-effect correlation was studied using Partial Least Squares(PLS)to explore the active ingredients of Ligustri Lucidi Fructus by investigating the relationship between HPLC spectrum and antioxidant activity. S1, S2, S15, S24, S27, S29, S32, S33 and S35 were characteristic compounds in 35 matching characteristic chromatograms which were positive relationship with scavenging DPPH free radical activity. S1, S2, S5, S8, S16, S27 and S33 were significantly positively related to scavenge ABTS free radical activity. S12, S20, S22, S28, S30, S31, S32 and S34 were significantly positively related to restore Fe³⁺ activity. Among the chromatographic peaks, S1, S2, S27 and S33were positively related to scavenge DPPH free radical and ABTS free radical activity, and S32 was positively related to scavenge DPPH free radical and restore Fe³⁺ activity. S3, S19, S21, S22, S23, S33 and S34 were determined as salidroside, luteolin-7-O-glucoside, specnuezhenide, oleuropein, ligustroflavone, luteolin andapigenin, respectively. The results showed that although specnuezhenide and salidroside were stipulated index compounds to evaluate the quality of Ligustri Lucidi Fructus, the Ligustri Lucidi Fructus pharmcodynamic effect did not depend on the contents of those index components. The quality of traditional Chinese medicines(TCMs)should be determined by the compound groups associated with pharmcodynamic effect.

Topics: Antioxidants; Drugs, Chinese Herbal; Fruit; Glucosides; Ligustrum; Medicine, Chinese Traditional; Phenols; Pyrans

The experiment was designed to study the mechanism of increasing efficiency of Ligustrum lucidum steamed with wine. Rats in vivo with gastrointestinal perfusion model were used. The contents of salidroside and specnuezhenide in the fluid of gastrointestinal perfusion of rats were measured by HPLC at different time points after dosing. Then the K(a) and absorption percentage were calculated. Specnuezhenide could be detected in the fluid of gastrointestinal perfusion of specnuezhenide. The K(a) of the specnuezhenide and salidroside in the fetal intestines are 0.055 3 and 0.144 2 h(-1) respectively and the total absorptivity are 24.46% and 60.14% respectively after 4 hours. The K(a) in the stomach are 5.70 and 8.26 h(-1) respectively and the total absorptivity are 34.21% and 47.23% respectively after 4 hours. The experiment proved that specnuezhenide can be metabolized into salidroside which is more beneficial for gastrointestinal absorption. The experiment proved that specnuezhenide can be metabolized into salidroside both in the rat's stomach and the fetal intestine and compared with the specnuezhenide salidroside is more conducive to gastrointestinal absorption. The results suggested that the increasing efficiency on liver and kidney of L. lucidum steamed with wine has business with the fact that Specnuezhe nide is more conducive to the body after it is changed into salidroside.

Topics: Animals; Chemistry, Pharmaceutical; Gastrointestinal Tract; Glucosides; Intestinal Absorption; Male; Phenols; Pyrans; Rats; Rats, Sprague-Dawley

The fruits of Ligustrum lucidum (FLL) has long been used for the treatment of osteoporosis in China, but the antiosteoporotic compounds in FLL are still poorly understood. In this study, the alkaline phosphatase (ALP) activity-guided isolation of osteogenic components from FLL was carried out by using osteoblast-like UMR-106 cells. Eight compounds, namely tyrosol (1), tyrosyl acetate (2), hydroxytyrosol (3), salidroside (4), oleoside dimethyl ester (5), oleoside-7-ethyl-11-methyl ester (6), nuzhenide (7), and G13 (8), were isolated and identified. Further study showed that compounds 3, 4, 7, and 8 increased ALP activity in UMR-106 cells. Compounds 5, 6, and 7 promoted the proliferation of UMR-106 cells. The aqueous extract of FLL-activated ERα/β-mediated gene transcription, whereas the isolated compounds were inactive. All eight isolated compounds also exhibited antioxidative activity, with compounds 1, 2, and 3 being the most potent. These results indicate that the antiosteoporotic effect of FLL is derived from different compounds together with different mechanisms such as ER-dependent or independent pathways and antioxidative effects. Salidroside (4) and nuzhenide (7) warrant further investigation as new pharmaceutical tools for the prevention and treatment of osteoporosis.

Topics: Alkaline Phosphatase; Animals; Antioxidants; Bone Density Conservation Agents; Estrogens; Fruit; Glucosides; HeLa Cells; Humans; Ligustrum; Osteoblasts; Osteoporosis; Phenols; Phytotherapy; Plant Extracts; Pyrans; Rats; Receptors, Estrogen