lignans and rhein

Intestinal obstruction (IO) is a kind of acute abdomen with high morbidity and mortality. Patients suffer from poor quality of life and tremendous financial pressure. Da-Cheng-Qi decoction (DCQD), a classical purgation prescription, has clinically been proven to be an effective treatment for IO.. Network pharmacology integrated with bioactive equivalence assessment was used to discover the quality marker (Q-marker) of DCQD against IO.. As there is hardly any targets recorded in database, thus the collection of IO targets was conducted by searching those of alternative diseases which have similar pathological symptoms with IO. In order to improve the reliability of the obtained targets, IO metabolomics data was introduced. Active compounds combination (ACC) was focused as potential Q-markers via component-target network analysis and function query from the identified components corresponding to the common targets. Bioequivalence between ACC and DCQD was assessed from the aspects of intestine motility (somatostatin secretion), inflammation (IL-6 secretion) and injury (wound healing assay) in vitro and was further validated in ileus rat model. PPI network analysis of core targets followed by gene pedigree classification and experimental validation confirmed the potential intervention pathway.. A combination of 11 ingredients, including emodin, physcion, aloe-emodin, rhein, chrysophanol, gallic acid, magnolol, honokiol, naringenin, tangeretin, and nobiletin was finally confirmed bioequivalence with DQCD to some extent and could serve as Q-markers for DCQD to attenuate IO. PI3K/AKT was verified as a possible affected pathway that DCQD exerted the effectiveness against IO.. For the disease with few recorded targets, searching those of alternative diseases which have similar pathological symptoms could be a feasible and effective approach. The proposed network pharmacology integrated bioactive equivalence evaluation paradigm is efficient to discover Q-marker of herbal formulae.

Topics: Algorithms; Animals; Anthraquinones; Biomarkers, Pharmacological; Biphenyl Compounds; Data Mining; Drugs, Chinese Herbal; Flavanones; HT29 Cells; Humans; Intestinal Obstruction; Lignans; Male; Phosphatidylinositol 3-Kinases; Rats, Sprague-Dawley; Reproducibility of Results; Therapeutic Equivalency

BACKGROUND Acute pancreatitis (AP) is generally a self-limiting inflammatory disease, but is associated with a high mortality rate when severe. The present study aimed to investigate the effects of rhein and honokiol on AP. MATERIAL AND METHODS Thirty mice were randomly divided into 5 groups (n=6 per group): blank control, AP model, AP+rhein, AP+honokiol, and AP+rhein+honokiol. The AP model was prepared by intraperitoneal injection of cerulein and lipopolysaccharide (LPS). We observed the pathological changes of the pancreas by hematoxylin and eosin (H&E) staining. A mouse amylase kit was utilized to detect the level of amylase content in serum. Gas chromatography mass spectrometer analysis was performed to detect the differences in metabolites among the blank control, AP model, and AP+rhein+honokiol groups. RESULTS The serum amylase level was significantly higher in the AP model, which suggested that the AP model was constructed successfully. The AP+rhein+honokiol group had significantly reduced interstitial edema, inflammatory cell infiltration, hemorrhage, and necrosis. In addition, the rhein and honokiol treatment influenced some of the metabolic pathways in AP, including riboflavin metabolism, glycerophospholipid metabolism, linoleic acid metabolism, and the pentose and glucuronate interconversions pathway. CONCLUSIONS This study showed that the combination of rhein and honokiol ameliorated pathological changes in the pancreas of mice with AP.

Topics: Amylases; Animals; Anthraquinones; Biphenyl Compounds; Disease Models, Animal; Enzyme Inhibitors; Lignans; Male; Metabolome; Mice; Mice, Inbred C57BL; Pancreas; Pancreatitis

To explore the pharmacokinetics and pharmacodynamics of Da-Cheng-Qi decoction (DCQD) in the liver of rats with severe acute pancreatitis (SAP) based on an herbal recipe tissue pharmacology hypothesis.. Healthy male Sprague-Dawley rats were randomly divided into a sham operation group (SOG); a model group (MG); and low-, median- and high-dose treatment groups (LDG, MDG, and HDG, respectively). Different dosages (6, 12 and 24 g/kg for the LDG, MDG, and HDG, respectively) of DCQD were administered to the rats with SAP. The tissue concentrations of aloe-emodin, rhein, emodin, chrysophanol, honokiol, rheo chrysophanol, magnolol, hesperidin, naringenin and naringin in the liver of the treated rats were detected by high-performance liquid chromatography tandem mass spectrometry. Alanine transaminase (ALT) and aspartate transaminase (AST) in serum, inflammatory mediators in the liver and pathological scores were evaluated.. The major components of DCQD were detected in the liver, and their concentrations increased dose-dependently. The high dose of DCQD showed a maximal effect in ameliorating the pathological damages, decreasing the pro-inflammatory mediators tumor necrosis factor-α and interleukin (IL)-6 and increasing anti-inflammatory mediators IL-4 and IL-10 in the liver. The pathological scores in the pancreas for the MG were significantly higher than those for the SOG (. DCQD could alleviate liver damage by altering the inflammatory response in rats with SAP based on the liver distribution of its components.

Topics: Acute Disease; Alanine Transaminase; Animals; Anthraquinones; Aspartate Aminotransferases; Biphenyl Compounds; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Emodin; Flavanones; Hesperidin; Inflammation; Lignans; Liver; Male; Pancreatitis; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

The medicinal herb formulation Da-Cheng-Qi decoction (DCQD) has been shown to ameliorate the severity of acute pancreatitis by regulating an apoptosis-necrosis switch in cells. The active components responsible for this effect and their detailed mechanism of action remain unclear. Here we determine the pharmacokinetic characteristics of the four most abundant compounds in DCQD using a rat model of severe acute pancreatitis. Acute pancreatitis-like symptoms were first induced in rats and then they were given DCQD orally. Rhein was found in rat serum at much higher levels than magnolol, hesperidin, or naringin, even though it was the least abundant of the four compounds in the DCQD. We also examined pharmacodynamics in AR42J cells stimulated with 10(-8) M cerulein as a cellular model of acute pancreatitis. After pretreating AR42J cells with individual compounds and then exposing them to cerulein, we determined cell viability, levels of apoptosis and necrosis, and numbers of cells positive for reactive oxygen species (ROS). Pretreatment with any of the four DCQD compounds increased cell viability and the apoptosis index, while also reducing necrosis and ROS generation. The compounds showed maximal effect in AR42J cells around the same time that they showed maximum serum concentration in rats. Although all four components appear to play a role in an apoptosis-necrosis cellular switch in vitro, rhein may be the most bioactive DCQD ingredient.

Topics: Animals; Anthraquinones; Apoptosis; Biphenyl Compounds; Cells, Cultured; Disease Models, Animal; Drugs, Chinese Herbal; Flavanones; Hesperidin; Lignans; Male; Necrosis; Pancreas; Pancreatitis, Acute Necrotizing; Phytotherapy; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species

To investigate the effect of prescription compatibility on the pharmacokinetics of components from Dachengqi Decoction (DCQD, ) in rats.. Twenty-four male rats were randomly and equally divided into the DCQD group, Dahuang (Radix et Rhizoma Rhei, Polygonaceae) group, Houpo (Magnolia officinalis Rehd., Magnoliaceae) group, and Zhishi (Fructus Aurantii Immaturus, Rutaceae) group. The blood samples were collected before dosing and subsequently at 10, 15, 20, 30, 45 min, 1, 2, 4, 8, and 12 h following gavage. The levels of aloe-emodin, rhein, emodin, chrysophanol, honokiol, magnolol, hesperidin, and naringin in rat serum were quantified using a liquid chromatography tandem mass spectrometry (LC-MS/MS) method for pharmacokinetic study.. The area under the curve (AUC), mean retention time (MRT), the peak concentration (C(max)) of aloe-emodin, rhein, emodin, and chrysophanol in the DCQD group were significantly different compared with the Dahuang group (P <0.05, respectively). The mean plasma concentration, C(max), and the absorption of Dahuang's component in the DCQD group were obviously lower at each time point than those in the Dahuang group, while the elimination process of Dahuang's component was obviously delayed (P <0.05). Half-lives of aloe-emodin, chrysophanol, and rhein were also extended in the DCQD group (P <0.05, respectively). In the DCQD group, the mean plasma concentration, AUC, C(max) and absorption of honokiol, and magnolol were significantly lower (P <0.01, respectively) at each time point than those in the Houpo group, while the drug distribution half-life time (T(1/2α)), the drug eliminated half-life time (T(1/2β)), MRT, and time of peak concentration (T(max)) were significantly delayed (P <0.05, respectively). Pharmacokinetic parameters of hesperidin and naringin in the Zhishi group were not significantly different as compared with the DCQD group (P >0.05, respectively), while the MRT of naringin was significantly longer.. The compatibility in Chinese medicine could affect the drug's pharmacokinetics in DCQD, which proves that the prescription compatibility principle of Chinese medicine formulations has its own pharmacokinetic basis.

Topics: Administration, Oral; Animals; Anthraquinones; Biphenyl Compounds; Drug Incompatibility; Emodin; Flavanones; Hesperidin; Lignans; Male; Plant Extracts; Rats; Rats, Sprague-Dawley

Da-Cheng-Qi decoction (DCQD) is a purgative compound prescription used in China and East Asia. In this paper, pharmacokinetic differences of six major active components (rhein, emodin, aloe-emodin, magnolol, naringenin and hesperetin) between DCQD and its three constitutional herbal medicines, i.e., Radix et Rhizoma Rhei, Cortex Magnoliae officinalis and Fructus Aurantii Immaturus were investigated in rats after oral administration. Plasma samples were analyzed for the quantification of the six active components using validated LC-MS/MS methods. Unpaired Student's t-test was used for statistical comparison. Significant differences (p < 0.05) in the main pharmacokinetic parameters for rhein, emodin, aloeemodin, magnolol, naringenin and hesperetin were found between DCQD and the decoction of its constitutional single herbal medicines, which demonstrated the presence of drug-drug interactions between these constitutional raw materials of DCQD occurring either in the procedure of decoction or during ADME process.

Topics: Animals; Anthraquinones; Area Under Curve; Biphenyl Compounds; Chromatography, Liquid; Drugs, Chinese Herbal; Emodin; Female; Flavanones; Hesperidin; Lignans; Male; Plant Extracts; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry

To investigate the effect of severe acute pancreatitis (SAP) on pharmacokinetics of Da-Cheng-Qi Decoction (DCQD) components in rats.. Rats were divided into SAP group and sham-operation group as a control group (n = 6). Rhein, chrysophanol, rheochrysidin, magnolol, hesperidin and naringin in DCQD were quantified in rat serum by high performance liquid chromatography tandem mass spectrometry for studying their pharmacokinetics.. Early absorption of each DCQD component was tended to degrade in SAP group after treatment with DCQD by gavage. The C(max) (chrysophanol, P = 0.0059; rheochrysidin, P = 0.0288; magnolol, P = 0.0487; hesperidin, P = 0.0277; naringin, P = 0.0023) and AUC (rhein, P = 0.0186; chrysophanol, P = 0.0013; magnolol, P = 0.001; hesperidin, P = 0.0081; naringin, P = 0.0272) of DCQD component were obviously lower in SAP group than in control group. The T(1/2alpha) of chrysophanol and rheochrysidin (P = 0.0467 and 0.0005, respectively) and T(max) of chrysophanol and rheochrysidin (P = 0.0101 and 0.0037, respectively) lasted longer in SAP group than in control group.. SAP can significantly impact the absorption of DCQD components in rats and their pharmacokinetic parameters.

Topics: Animals; Anthraquinones; Anti-Inflammatory Agents, Non-Steroidal; Biphenyl Compounds; Enzyme Inhibitors; Flavanones; Glucosides; Hesperidin; Humans; Lignans; Male; Molecular Structure; Mutagens; Pancreatitis, Acute Necrotizing; Plant Extracts; Random Allocation; Rats; Rats, Sprague-Dawley

To study the chemical constituents and volatile oil of Xiaochengqi decoction.. The constituents in decoction were separated by means of column chromatography and their structures were identified by spectral data and compared with literature data. As well as the volatile oil of Xiaochengqi Fang were analyzed and identified by GC-MS.. Eleven compounds were isolated and identified as chrysophanol (1), physcion (2), magnolol (3), beta-sitosterol (4), sitosterol trans-cinnamic acid (5), emodin (6), aloe emodin (7), rhein (8), gallic acid (9), chrysophanol-8-O-beta-D-glucopyranoside (10), aurantiamarin (11). The volatile oils extracted with steam distillation from Xiaochengqi were identified 67 components, and the main components are including.. All of the eleven compounds were isolated from Xiaochengqi decoction for the first time and the study on their activities in Chinese prescription is being carried out. D-limonene (42.61%), p-cymene (16.43%), and 8-terpinene (14.46%).

Topics: Anthraquinones; Biphenyl Compounds; Cinnamates; Cyclohexenes; Cymenes; Drugs, Chinese Herbal; Emodin; Gallic Acid; Gas Chromatography-Mass Spectrometry; Lignans; Limonene; Monoterpenes; Oils, Volatile; Sitosterols; Terpenes

A rapid, sensitive and specific liquid chromatography-electrospray ionization/tandem mass spectrometry (LC-ESI/MS/MS) method has been developed and validated for simultaneous determination of five active constituents (including magnolol, honokiol, rhein, emodin and aloe-emodin) from Da-Cheng-Qi decoction (DCQD) in rat plasma. After the addition of gliquidone as the internal standard (IS), plasma samples were prepared by one-step protein precipitation using methanol and separated by HPLC on a short reversed phase C(18) column packed with smaller particles (100 mm x 3.0 mm, 3.5 microm) using a mobile phase of methanol-0.1% formic acid aqueous solution (70:30, v/v). Analytes were determined in a triple-quadrupole mass spectrometer in the selected reaction-monitoring (SRM) mode using electrospray source with negative mode. The method was proved to be rapid, sensitive, specific, accurate and reproducible and has been successfully applied to the determination of the five compounds in rat plasma after oral administration of low dose DCQD for pharmacokinetic study.

Topics: Administration, Oral; Animals; Anthraquinones; Biphenyl Compounds; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Emodin; Female; Lignans; Male; Plant Extracts; Rats; Rats, Sprague-Dawley; Tandem Mass Spectrometry