A combination of LC-MS technology and activity evaluation was used to identify the antipyretic ingredients in rhubarb. The rat model of fever was established with dried yeast and then was administered ethanol extract and different polar fractions of rhubarb. Next, the anal temperature of these rats was measured and recorded at 0.5, 1, 2, 3, 4 and 5 h after administration, and the inhibition rate of each part on the rise of body temperature was calculated. The inhibition rate is higher and the antipyretic effect is better. The chemical composition of the effective fraction was analyzed with UPLC-ESI-Orbitrap-MS/MS technology. Compared with the model group, the increase of body temperature of ethanol extract group all reduced at each measurement time especially after 3 h, and the inhibition rate were 38.7%(P<0.05), 78.2%(P<0.01) and 72.4%(P<0.01) at 3 h, 4 h, and 5 h after administration, respectively. Both n-butanol and water fraction showed some antipyretic activity in the early stage, with the inhibition rate of 28.1%(P<0.01) and 24.9%(P<0.05) at 1 h after administration, respectively, while other fractions were not active. Thirty-three and twelve compounds were identified from n-butanol and water fraction by LC-MS/MS analysis, respectively, including ten tannins, fifteen anthraquinone glycosides, four anthrone glycosides, one phenolic glycoside, one naphthaline derivative, one anthraquinone and one sucrose. These results revealed that rhubarb had antipyretic activity on rats, and tannin and anthraquinone glycosides were the main active ingredients inside.
Animals ; Anthraquinones ; Antipyretics/pharmacology* ; Chromatography, Liquid ; Fever/drug therapy* ; Glycosides ; Plant Extracts/pharmacology* ; Plants, Medicinal/chemistry* ; Rats ; Rheum/chemistry* ; Tandem Mass Spectrometry ; Tannins

Anthraquinones,dianthrones and tannins are the main active ingredients of Rheum tanguticum. In this study the three components were determined by HPLC,and the results were analyzed by multiple comparisons,principal components analysis(PCA)and correspondence analysis(CA). The results showed that the contents of components in different growing areas and types(wild and cultivated) reached a significant level(P<0. 05). Baiyu county,Xiaojin county and Ruoergai county had obvious advantages in the accumulation of catechin hydrate,rhien and sensenoside A respectively. The principal component was different in two growing type and the wild environment was conducive to combined anthraquinones accumulation. For active components,normalized planting was better than retail cultivating. Therefore,the effect on the accumulation of chemical components in Rh. tangusticum,should be taken into full account in the selection of the cultural base of Rh. tanguticum. The standardized cultivating is superior to retail cultivating in terms of the accumulation of active ingredients,and standardized planting is inferior to the wild.
Anthraquinones ; analysis ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; analysis ; Phytochemicals ; analysis ; Plants, Medicinal ; chemistry ; Rheum ; chemistry ; Tannins ; analysis

The dose-toxicity-effect relationship between licorice combined with rhubarb in purgation was studied. A total of 108 ICR mice were divided into control group,model group,positive group,low,medium and high-dose rhubarb groups,and low,medium and high-dose rhubarb-liquorice decoction group. After 6 days of continuous administration of loperamide hydrochloride,the constipation model of mice was replicated,and each group was given lactulose,different doses of rhubarb and rhubarb-liquorice decoction for 14 days. After administration,the defecation characteristics,blood biochemistry,liver,kidney and colon pathological changes in each group were compared. Based on the objective weight given by factor analysis,the dose-toxicity-effect relationship was comprehensively analyzed by multi-index scoring method. Two common factors were extracted by factor analysis,representing effect and toxicity respectively. The results showed that rhubarb could exert a diarrhea effect at the dosage of 1/2,2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,increase the defecation volume and the intestinal tract propulsion rate,reduce the time of anal and the oral transmission,and increase the water content of feces. The combination with licorice could alleviate its diarrhea effect,especially at the dosage of 1/2 times of the high limit set forth in the Chinese Pharmacopoeia. However,rhubarb showed obvious hepatic and colon toxicities at the dosage of 2 and 8 times of the high limit set forth in the Chinese Pharmacopoeia,and the combination with licorice could significantly reduce its toxicity. It shows that licorice has a " mediating" effect on rhubarb by alleviating the purgation property and reducing the toxicity.
Animals ; Cathartics ; pharmacology ; Colon ; Dose-Response Relationship, Drug ; Glycyrrhiza ; chemistry ; Kidney ; Liver ; Mice ; Mice, Inbred ICR ; Plant Extracts ; pharmacology ; Rheum ; chemistry ; Toxicity Tests

BackgroundGastrointestinal dysfunction plays a critical role in the prognosis of critically ill patients. Previous studies showed rhubarb, a traditional Chinese herb, can protect the intestinal barrier function, prevent intestinal bacterial translocation, and promote gastrointestinal peristalsis, but the clinical studies are less. The aim of this study was to evaluate the effects of rhubarb on gastrointestinal dysfunction in critically ill patients.

MethodsFrom June 2015 to May 2017, a total of 368 critically ill patients with Grade I-III acute gastrointestinal injury (AGI) were enrolled in this study. Patients were divided into two groups according to the exposure factors (whether the patients received rhubarb treatment): the rhubarb group and the usual treatment group. Clinical data were collected within the first 24 h of the Intensive Care Unit (ICU) admission and 7 days after treatment. Survival data on day 28 after ICU admission and the durations of ICU and total hospitalization were also collected. Propensity score matching (PSM) was conducted to reduce confounding bias between the groups. The logistic regression was conducted to screen the influence factors.

ResultsThe eligible patients were divided into rhubarb group (n = 219, 59.5%) and usual treatment group (n = 149, 40.5%). Before PSM, the remission rate of feeding intolerance in rhubarb group and usual treatment group were 59.8% and 39.6%, respectively. After PSM, the remission rate of feeding intolerance in rhubarb group and usual treatment group was 77.9% and 30.9%, respectively. The remission rates of feeding intolerance in rhubarb group were significantly higher than those in the usual treatment group (all P < 0.05). Compared with the usual treatment group, the rhubarb group had a higher rate of AGI improvement, lower level of C-reactive protein, shorter stay in ICU before and after PSM (P < 0.05). There was no significant difference in 28-day mortality between rhubarb and usual treatment groups before and after PSM (48 vs. 33, P = 0.959; and 16 vs. 21, P = 0.335). The logistic regression analysis showed that the single factor, whether receiving rhubarb therapy, affected the proportion of patients whose enteral nutrition needs ≥83.7 kJ·kg·d after 7 days of treatment (odds ratio: 7.908, 95% confidence interval: 3.661-17.083, P < 0.001). No serious adverse effects were found in two groups.

ConclusionsThe rhubarb might significantly improve feeding tolerance and relieve gastrointestinal dysfunction in critically ill patients, without serious adverse reactions. It provided proof for the treatment of gastrointestinal dysfunction with rhubarb during clinical practice.

APACHE ; Adult ; Aged ; Critical Illness ; Female ; Gastrointestinal Diseases ; metabolism ; pathology ; Humans ; Intensive Care Units ; statistics & numerical data ; Male ; Middle Aged ; Plant Extracts ; chemistry ; therapeutic use ; Propensity Score ; Retrospective Studies ; Rheum ; chemistry

BACKGROUNDLeakage of the intestinal mucosal barrier may cause translocation of bacteria, then leading to multiorgan failure. This study hypothesized that rhubarb monomers might protect the gut mucosal barrier in sepsis through junction proteins.

METHODSHealthy male Sprague-Dawley rats (weighing 230-250 g) under anesthesia and sedation were subjected to cecal ligation and perforation (CLP). After surgical preparation, rats were randomly assigned to eight groups (n = 6 or 8 each group): sham group (Group A: normal saline gavage); sepsis group (Group B: normal saline gavage); Group C (intraperitoneally, dexamethasone 0.5 mg/kg) immediately after CLP surgery; and rhubarb monomer (100 mg/kg in normal saline)-treated groups (Group D: rhein; Group E: emodin; Group F: 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid; Group G: 1-O-caffeoyl-2-(4-hydroxy-O-cinnamoyl)-D-glucose; and Group H: daucosterol linoleate). Animals were sacrificed after 24 h. Intestinal histology, lactulose, mannitol concentrations were measured, and zonula occludens (ZO)-1, occludin and claudin-5 transcription (polymerase chain reaction), translation (by Western blot analysis), and expression (by immunohistochemistry) were also measured.

RESULTSIntestinal histology revealed injury to intestinal mucosal villi induced by sepsis in Group B, compared with Group A. Compared with Group A (0.17 ± 0.41), the pathological scores in Groups B (2.83 ± 0.41, P < 0.001), C (1.83 ± 0.41, P < 0.001), D (2.00 ± 0.63, P < 0.001), E (1.83 ± 0.41, P < 0.001), F (1.83 ± 0.75, P < 0.001), G (2.17 ± 0.41, P < 0.001),and H (1.83 ± 0.41, P < 0.001) were significantly increased. Lactulose/mannitol (L/M) ratio in Group B (0.046 ± 0.003) was significantly higher than in Group A (0.013 ± 0.001, P< 0.001) while L/M ratios in Groups C (0.028 ± 0.002, P< 0.001), D (0.029 ± 0.003, P< 0.001), E (0.026 ± 0.003, P< 0.001), F (0.027 ± 0.003, P< 0.001), G (0.030 ± 0.005, P< 0.001), and H (0.026 ± 0.002, P< 0.001) were significantly lower than that in Group B. ZO-1, occludin and claudin-5 transcription, translation, and expression in Group B were significantly lower than that in Group A (P < 0.001), but they were significantly higher in Groups C, D, E, F, G, and H than those in Group B (P < 0.05).

CONCLUSIONRhubarb monomer treatment ameliorated mucosal damage in sepsis via enhanced transcription, translation, and expression of junction proteins.

Animals ; Claudin-5 ; metabolism ; Intestinal Mucosa ; drug effects ; metabolism ; Lactulose ; metabolism ; Male ; Mannitol ; metabolism ; Occludin ; metabolism ; Plant Extracts ; chemistry ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Rheum ; chemistry ; Sepsis ; drug therapy ; metabolism ; Zonula Occludens-1 Protein ; metabolism

BACKGROUNDIntact endothelial structure and function are critical for maintaining microcirculatory homeostasis. Dysfunction of the latter is an underlying cause of various organ pathologies. In a previous study, we showed that rhubarb, a traditional Chinese medicine, protected intestinal mucosal microvascular endothelial cells in rats with metastasizing septicemia. In this study, we investigated the effects and mechanisms of rhubarb on matrix metalloproteinase-9 (MMP9)-induced vascular endothelial (VE) permeability.

METHODSRhubarb monomers were extracted and purified by a series of chromatography approaches. The identity of these monomers was analyzed by hydrogen-1 nuclear magnetic resonance (NMR), carbon-13 NMR, and distortionless enhancement by polarization transfer magnetic resonance spectroscopy. We established a human umbilical vein endothelial cell (HUVEC) monolayer on a Transwell insert. We measured the HUVEC permeability, proliferation, and the secretion of VE-cadherin into culture medium using fluorescein isothiocyanate-dextran assay, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, and enzyme-linked immunosorbent assay, respectively, in response to treatment with MMP9 and/or rhubarb monomers.

RESULTSA total of 21 rhubarb monomers were extracted and identified. MMP9 significantly increased the permeability of the HUVEC monolayer, which was significantly reduced by five individual rhubarb monomer (emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-β-D-glucose, daucosterol linoleate, and rhein) or a combination of all five monomers (1 μmol/L for each monomer). Mechanistically, the five-monomer mixture at 1 μmol/L promoted HUVEC proliferation. In addition, MMP9 stimulated the secretion of VE-cadherin into the culture medium, which was significantly inhibited by the five-monomer mixture.

CONCLUSIONSThe rhubarb mixture of emodin, 3,8-dihydroxy-1-methyl-anthraquinone-2-carboxylic acid, 1-O-caffeoyl-2-(4-hydroxyl-O-cinnamoyl)-β-D-glucose, daucosterol linoleate, and rhein, at a low concentration, antagonized the MMP9-induced HUVEC monolayer permeability by promoting HUVEC proliferation and reducing extracellular VE-cadherin concentrations.

Cadherins ; metabolism ; Capillary Permeability ; drug effects ; Cell Line ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; Rheum ; chemistry

Viral infections are the major causes of morbidity and mortality in elderly people and young children throughout the world. The most common pathogens include coxsackie virus (CV) and respiratory syncytial virus (RSV). However, no antiviral agents with low toxicity and drug resistance are currently available in clinic therapy. The present study aimed to examine the antiviral activities of emodin (an ingredient of Rheum palmatum) against CVB5 and RSV infections, in an attempt to discover new antiviral agents for virus infection. The monomer emodin was extracted and isolated from Rheum palmatum. The antiviral activities of emodin on HEp-2 cells were evaluated, including virus replication inhibition, virucidal and anti-absorption effects, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tet-razolium bromide (MTT) assay and plaque reduction assay (PRA). The kinetics of virus inhibition by emodin in a period of 14 h was further determined by plaque assay and quantitative real time PCR (qPCR). Cytokine (IFN-γ, TNF-α) mRNA expressions after emodin treatment (7.5, 15, 30 μmol/L) were also assessed by qPCR post-infection. The results showed that emodin had potent inhibitory activities against CVB5 and RSV, with the 50% effective concentration (EC50) ranging from 13.06 to 14.27 μmol/L and selectivity index (SI) being 5.38-6.41 μmol/L. However, emodin couldn't directly inactivate the viruses or block their absorption to cells. It acted as a biological synthesis inhibitor against CVB4 and RSV in a concentration- and time-dependent manner, especially during the first 0-4 h post-infection. Moreover, emodin could decrease the mRNA expression of IFN-α but enhance TNF-γ expression significantly compared to the viral controls in vitro. Our results provide a molecular basis for development of emodin as a novel and safe antiviral agent for human enterovirus and respiratory virus infection in the clinical therapy.
Antiviral Agents ; pharmacology ; Cell Line ; Cell Line, Tumor ; Emodin ; pharmacology ; Enterovirus B, Human ; drug effects ; physiology ; Humans ; In Vitro Techniques ; Respiratory Syncytial Viruses ; drug effects ; physiology ; Rheum ; chemistry ; Virus Replication

The research aimed to evaluate the intestinal absorption of alkaloids extracted by decoction and alcohol extraction proces- ses from Rhizoma Coptidis-Rheum rhabarum herbal pair via everted gut sacs. Berberine, palmatine, coptisine and epiberberine were the main alkaloids in this herbal pair and taken as the standard indexes in the quantitative analysis with multi-components by single marker (QAMS) method, in order to calculate absorption rate constant (Ka) and evaluate intestinal absorption characteristics of these four alkaloids extracted by different extraction methods in different intestinal segments in rats. The results showed that the four alkaloids extracted by two different processes in high, medium and low doses had linear absorption properties in the small intestine segment, which conformed to zero-order absorption rate, intestinal segment than 0.99. The absorption rate constant (Ka) of decoction group was higher than that of alcohol extraction group.
Alkaloids ; pharmacokinetics ; Animals ; Coptis ; chemistry ; Intestinal Absorption ; Male ; Rats ; Rats, Sprague-Dawley ; Rheum ; chemistry

Rhubarb is a traditional Chinese medicine (TCM), wildly used in treating the disease of hyperlipidemia. However, its components are complicated, so that it is still difficult to clear the specific roles of its various components in blood lipids regulation in. So we decide to systematically study the anti- hyperlipidemia mechanism of rhubarb. We integrated multiple databases, based on entity grammar systems model, constructed molecular interaction network between the chemical constituents of rhubarb and hyperlipidemia. The network includes 231 nodes and 638 edges. Thus we infer the interactions of active targets and disease targets to clarify the anti-hyperlipidemia mechanism. And find that rhubarb can promote excretion of cholesterol; inhibit clotting factors and improve blood circulation; inhibit the release of inflammatory cytokines and maintain fat metabolism balance; inhibit cholesterol and triglyceride synthesis; and other ways to achieve lipid-lowering effect. Thus this study provides reference for novel drug development and component compatibility, and also gives a new way for the systematically study of acting mechanism of traditional Chinese medicine.
Animals ; Databases, Factual ; Drugs, Chinese Herbal ; administration & dosage ; chemistry ; Gene Regulatory Networks ; drug effects ; Humans ; Hyperlipidemias ; drug therapy ; genetics ; metabolism ; Hypolipidemic Agents ; administration & dosage ; chemistry ; Lipid Metabolism ; Rheum ; chemistry ; Signal Transduction ; drug effects

OBJECTIVETo comparatively study the effects of Rhubarbs from different regions on blood lipid and antioxi dation of hyperlipidemia rats.

METHODSMale rats were randomly divided into 9 groups ( n = 8) and fed with high-fat diet to replicate the hyperlipidemia model. Meanwhile, Rheum tanguticum was administrated intragastrically at two doses (3.0 g/kg and 1.0 g/kg), once a day for continuous 28 days. The effects of Rheum tanguticum planted in Gannan (RT-GN), Rheum tanguticum planted in Xinin (RT-XN) and Rheum plmatum planted in Lixian (RP-LX) were evaluated through detecting the parameters of blood lipids, blood viscosity and antioxidant system.

RESULTST-GN, RT-XN and RP-LX in the range of 1.0-3.0 g/kg could decrease the blood levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and malonaldehyde (MDA) in blood. Besides, they could reduce blood viscosity, increase high density lipoprotein (HDL) level and upregulate the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Interestingly, their effects on blood viscosity was obviously in a dose dependent manner. In addition, the effects of RT-GN on LDL, MDA and blood viscosity were not significantly different from those of RT-XN and better than those of RP-LX.

CONCLUSIONThe RT has better hypolipidemic effects than the RP, but RT-GN and RT-XN are not different from the above effects.

Animals ; Antioxidants ; metabolism ; Blood Viscosity ; Cholesterol ; blood ; Diet, High-Fat ; Disease Models, Animal ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Glutathione Peroxidase ; metabolism ; Hyperlipidemias ; drug therapy ; Lipids ; blood ; Lipoproteins, HDL ; blood ; Lipoproteins, LDL ; blood ; Male ; Malondialdehyde ; blood ; Rats ; Rheum ; chemistry ; Superoxide Dismutase ; metabolism ; Triglycerides ; blood