iridoids and rhein

Yīn-Chén-Hāo decoction (YCHD) is a traditional Chinese medicine formula composed of capillaris (

Topics: Animals; Anthraquinones; Anti-Inflammatory Agents; Antiviral Agents; Artemisia; Ascites; Chlorogenic Acid; Clinical Trials as Topic; Coumarins; Drugs, Chinese Herbal; Emodin; Fatty Liver; Gardenia; Humans; Iridoids; Liver Diseases; Plant Extracts; Rheum

Topics: Animals; Anthraquinones; Chromatography, Liquid; Coumarins; Drug Evaluation, Preclinical; Herbal Medicine; Iridoids; Male; Rats; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry

Hollow fiber cell fishing (HFCF) based on human hepatoma cell HepG-2 or human renal tubular cell ACHN coupled with high performance liquid chromatography/ultraviolet detection (HPLC/UV) was developed and used for simultaneous study of the major antitumor active components in a formula of Yinchenhao decoction (YCHD) in vitro and in vivo, and in its constituent herbs, namely, Artemisia capillaris Thunb, Gardenia jasminoides Ellis, Radix et Rhizoma Rhei in vitro. Before application, chlorogenic acid, geniposide, p-hydroxyacetophenone, crocin and rhein were chosen as model compounds, the various validations, e.g., cell growth and cell viability on the fiber inner wall, binding between fiber active center and component, repeatability of retention time or relative peak area of the active components were investigated. We screened and identified the major antitumor active components of YCHD, verified their synergetic or antagonistic effect, correlated the major active components between in vitro and in vivo and determined major effective components. Our study will serve as a valuable reference in probing the antitumor material basis of YCHD and its three constituent herbs, as well as in identifying novel clinical aspects of traditional Chinese medicines. The results showed that HCFC-HPLC is a simple, rapid, and reliable method that simultaneously researches the interaction between multiple targets and multiple components of herbal medicine.

Topics: Acetophenones; Animals; Anthraquinones; Antineoplastic Agents; Carotenoids; Cell Culture Techniques; Cell Proliferation; Cell Survival; Chlorogenic Acid; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Hep G2 Cells; Humans; Iridoids; Male; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sensitivity and Specificity; Tissue Distribution

Topics: Anthraquinones; Chromatography, High Pressure Liquid; Coumarins; Drugs, Chinese Herbal; Iridoids; Microscopy; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry

Herb pair serves as the basic building block of a traditional Chinese medicine (TCM) formula. The rhubarb-gardenia herb pair (RGHP), composed of rhubarb and gardenia, has meaningful clinical effects to cure cholestasis diseases. This study was designed to confirm the expected synergistic effects of RGHP at pharmacodynamic and pharmacokinetic levels.. Thirty male Sprague-Dawley rats were divided into control, model and drug-treated groups. After intragastrically administrated with α-naphthylisothiocyanate (ANIT) to induce cholestasis, rats were treated with rhubarb, gardenia or RGHP. For pharmacodynamic study, biochemical and histopathological tests were performed to assess the hepatoprotective effects. While for pharmacokinetic study, a LC-MS method was developed for determination of five main chemical markers, namely genipin, rhein, aloe emodin, emodin and chrysophanol in rat plasma.. The biochemical and histopathological tests suggested that RGHP exerted enhanced hepatoprotective effects against the ANIT-induced cholestasis compared with single herbs. The pharmacokinetic study indicated RGHP could significantly elevate systemic exposure level and prolong retention time of five markers in comparison with rhubarb or gardenia alone.. The present study demonstrated the synergistic effects of RGHP in ANIT-induced cholestatic rats at pharmacodynamic and pharmacokinetic levels, and has significant enlightenments for the rational use of the related TCM formulas containing RGHP.

Topics: 1-Naphthylisothiocyanate; Alanine Transaminase; Alkaline Phosphatase; Animals; Anthraquinones; Aspartate Aminotransferases; Bilirubin; Cholestasis; Drug Synergism; Emodin; Fruit; Gardenia; Iridoids; Liver; Male; Plant Extracts; Protective Agents; Rats, Sprague-Dawley; Rheum; Rhizome

To enhance the therapeutic efficacy and reduce the adverse effects of traditional Chinese medicine, practitioners often prescribe combinations of plant species and/or minerals, called formulae. Unfortunately, the working mechanisms of most of these compounds are difficult to determine and thus remain unknown. In an attempt to address the benefits of formulae based on current biomedical approaches, we analyzed the components of Yinchenhao Tang, a classical formula that has been shown to be clinically effective for treating hepatic injury syndrome. The three principal components of Yinchenhao Tang are Artemisia annua L., Gardenia jasminoids Ellis, and Rheum Palmatum L., whose major active ingredients are 6,7-dimethylesculetin (D), geniposide (G), and rhein (R), respectively. To determine the mechanisms underlying the efficacy of this formula, we conducted a systematic analysis of the therapeutic effects of the DGR compound using immunohistochemistry, biochemistry, metabolomics, and proteomics. Here, we report that the DGR combination exerts a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of hepatic injury. Thus, DGR synergistically causes intensified dynamic changes in metabolic biomarkers, regulates molecular networks through target proteins, has a synergistic/additive effect, and activates both intrinsic and extrinsic pathways.

Topics: Animals; Anthraquinones; Biomarkers; Drug Evaluation, Preclinical; Drug Synergism; Drug Therapy, Combination; Drugs, Chinese Herbal; Iridoids; Liver; Liver Diseases; Male; Medicine, Chinese Traditional; Metabolome; Metabolomics; Molecular Targeted Therapy; Proteome; Proteomics; Rats; Rats, Wistar; Umbelliferones

Increasing evidence has demonstrated that multidrug combinations could amplify the therapeutic efficacies of each agent. Interestingly, the pharmacological effect of traditional Chinese medicine (TCM) is usually attributed to the drug-interaction property (synergism) of multiple active constituents. Pharmacokinetics is a useful means of evaluating the drug interactions of major active compounds in TCM. A simple, sensitive and reliable RP-HPLC-DAD method has been developed to simultaneously quantify 6,7-dimethylesculetin (D), geniposide (G) and rhein (R), which are the active ingredients in Yin-Chen-Hao-Tang (YCHT), performing drug-interaction pharmacokinetics studies in vivo. Plasma samples were prepared using methanolic precipitation, a filtration step, and then injection of the methanolic extract onto a Nova-Pak C₁₈ Guard-Pak™ guard column with a gradient mobile phase. Triple-wavelength diode array detection was set at λ(max) values of 343 nm for D, 241 nm for the G, and 259 nm for R. Our results successfully demonstrate that this method has excellent and satisfactory selectivity, sensitivity, linearity, precision, accuracy and recovery. In healthy rats, the estimated pharmacokinetic parameters (i.e. C(max) , AUC and Cl) of D, G and R, when administered with COC (a combination of D, G and R), were C(max) 16.05 mg/L, AUC 108.96 mg h/L and Cl 0.36 L/h for D; C(max) 9.35 mg/L, AUC 64.71 mg h/L and Cl 0.88 L/h for G; and C(max) 14.18 mg/L, AUC 57.98 mg h/L and Cl 1.77 L/h for R. Here, we report that the COC combination could significantly increase the plasma level and slow the elimination rate compared with any one or two of the three individual compounds, which may indicate a drug-drug interaction.

Topics: Animals; Anthraquinones; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Coumarins; Drug Synergism; Drugs, Chinese Herbal; Iridoids; Linear Models; Male; Models, Chemical; Rats; Rats, Wistar; Reproducibility of Results; Sensitivity and Specificity

6,7-Dimethylesculetin (D), geniposide (G) and rhein (R) are the three major active ingredients of Yin-Chen-Hao-Tang (YCHT), a famous Chinese herbal formula, which has been shown to be clinically effective for treating hepatic injury (HI) syndrome. The present study was conducted to investigate the therapeutic and synergistic effects of COC (combination of D, G and R) on HI rats by combining pharmacokinetic with biochemical analysis strategy. Plasma was analyzed by using reversed-phase high performance liquid chromatography (RP-HPLC). Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models were built to evaluate the therapeutic and synergistic effects of COC at the biochemical level. Here, we report that the COC combination could increase the plasma level, slow elimination rate, exert a more robust therapeutic effect than any one or two of the three individual compounds by hitting multiple targets in a rat model of HI. Overall, this beneficially accounts for the popular view that traditional Chinese medicine (TCM) formula usually takes multi-component to exert their therapeutic effects. We suggest that dissecting the mode of action of clinically effective formula to be capable of producing a sufficient effect at low doses.

Topics: Animals; Anthraquinones; Artemisia; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Chromatography, High Pressure Liquid; Drug Combinations; Drug Synergism; Drugs, Chinese Herbal; Gardenia; Iridoids; Least-Squares Analysis; Magnoliopsida; Male; Phytotherapy; Principal Component Analysis; Rats; Rats, Wistar; Rheum; Umbelliferones