stilbenes and rhapontin

Rhaponticin is a stilbenoid glucoside compound, found in medicinal plant of rhubarb rhizomes. Rhapontigenin (RHAG), the stilbene aglycone metabolite of rhaponticin, has shown various biological activities including anticancer activities to act a potential human cytochrome P450 inhibitor, antihyperlipidemic effect, anti-allergic action, antioxidant and antibacterial activities. Moreover, it was reported to scavenge intracellular Reactive Oxygen Species (ROS), the 1,1-Diphenyl-2-Picrylliydrazyl (DPPH) radical, and Hydrogen Peroxide (H2O2). Meanwhile, RHAG exhibited the inhibitory activity for the synthesis of DNA, RNA and protein, and also presented the capacity of inducing morphological changes and apoptosis of C. albicans. Here, the structure, pharmacokinetics, pharmacological effects as well as underlying mechanisms of rhaponticin and its metabolite, RHAG, have been extensively reviewed. This review will provide a certain reference value for developing the therapeutic drug of rhaponticin or RHAG.

Topics: Blood Proteins; Humans; Hydrogen Peroxide; Membrane Glycoproteins; Stilbenes

Parkinson's disease (PD) is a complex neurodegenerative illness associated with the loss or damage to neurons of the dopaminergic system in the brain. Few therapeutic approaches and considerable side effects of conventional drugs necessitate a new therapeutic agent to treat patients with PD. Rhaponticin is a natural hydroxystilbene, found in herbal plants such as Rheum rhaponticum, and known to have desirable biological activity including anti-inflammatory properties. However, the neuroinflammation on rhaponticin levels has only been investigated partially so far. So, the current study explored whether rhaponticin could ameliorate the pathophysiology observed in both the in vitro microglial BV-2 cells and the in vivo (1-methyl-4-phenyl-1,2,3,5-tetrahydropyridine [MPTP])-mediated PD model. The results show rhaponticin significantly attenuated lipopolysaccharide (LPS)-mediated microglial activation by suppressing nitric oxide synthase in conjunction with abridged reactive oxygen species production together with proinflammatory mediator reduction. In vivo rhaponticin treatment improves motor impairments as well as the loss of dopaminergic neurons in MPTP-treated mice possibly through suppression via mediators of inflammation. Taken together, these results offer evidence that rhaponticin exerts anti-inflammatory effects and neuroprotection in an LPS-induced microglial model and the MPTP-induced mouse models of PD.

Topics: Animals; Cell Line, Transformed; Dopaminergic Neurons; Male; Mice; MPTP Poisoning; Neuroprotective Agents; Stilbenes

The untreated systemic chronic inflammation leads to autoimmune diseases, hyperglycemia, cardiovascular diseases, type 2 diabetes, hypertension, osteoporosis, and so on. Phytochemicals effectively inhibit the inflammation, and numerous studies have proved that the phytocomponents possess anti-inflammatory property via inhibiting the cyclooxygenase and lipoxygenase signaling pathways. Rhaponticin is one such phytochemical obtained from the perennial plant Rheum rhaponticum L. belonging to Polygonaceae family. We assessed the anti-inflammatory potency of rhaponticin in endothelial cells induced with lipopolysaccharides (LPS). Four different endothelial cells induced with LPS were treated with rhaponticin and assessed for the nitric oxide generation. The cytotoxic potency of rhaponticin was evaluated in endothelial cells using the 3-(4,5-dimethylthizaol-2yl)-2,5-diphenyl tetrazolium bromide assay. The tumor necrosis factor-α (TNF-α) synthesis was quantified using the commercially available assay kit. The inflammatory signaling protein gene expression of TNF-α, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX2), and interleukin-1β (IL-1β) was analyzed with quantitative polymerase chain reaction (PCR) analysis. The gene expression of NADPH oxidase (NOX) cytoplasmic catalytic subunits gp91

Topics: Anti-Inflammatory Agents; Extracellular Signal-Regulated MAP Kinases; Human Umbilical Vein Endothelial Cells; Humans; Lipopolysaccharides; MAP Kinase Signaling System; NF-kappa B; Stilbenes

Rhaponticin is a constituent isolated from numerous medicinal herbs. It has been reported earlier that rhaponticin possesses numerous biological effects like antiallergic, antidiabetic, hepatoprotective, and antithrombosis. The goal of this exploration was to scrutinize the therapeutic potential of rhaponticin on ovariectomy (OVX)-triggered osteoporosis in rats. Female Sprague Dawley rats were arbitrarily allocated to a sham-operated control group I, group II, which underwent OVX, and groups III and IV that underwent OVX were administered with rhaponticin (10 and 20 mg/kg). Rhaponticin was supplemented orally after 4 weeks of OVX and continued for about 16 weeks. Our findings exhibit that rhaponticin prevented the BMD diminution of femurs, induced by OVX, and protected the worsening of trabecular microarchitecture that are assisted through a noteworthy decline in skeletal remodeling as noticed through the diminished status of bone markers in a dose-dependent manner (10 and 20 mg/kg). OVX rats treated with rhaponticin efficiently enhanced body weight, lipid profiles, uterine index, bone turnover markers, inflammatory markers, and augmented the incidence of calcium in the OVX rats. Rhaponticin was established to restrain the functions of acid phosphatase, estradiol, and bone gla protein in OVX rats. Also, rhaponticin displayed some beneficial effects on histomorphometric and histopathological examination. It was observed that tabular area and thickness were reinstated in sham control and rhaponticin-treated OVX rats. We recognized that rhaponticin did not induce a damaging outcome on the skeletal organization of OVX rats. Moreover, we denote that rhaponticin can be an exceptional agent for the treatment and deal with associated bone diseases.

Topics: Animals; Bone Density; Cancellous Bone; Female; Osteoporosis; Ovariectomy; Rats; Rats, Sprague-Dawley; Stilbenes

Oxidative stress and inflammation have long been considered to be responsible for the development and progression of diabetic retinopathy. On the other hand, rhaponticin (RN) has received scientific attention due to its various pharmacological properties. Keeping all these in view, the present study was performed to investigate the potential protective effects of RN on the retina in diabetic rats. Rats were randomly divided into three groups: control group rats, diabetic group rats, diabetic + RN (20 mg/kg body weight for 28 days through oral route) group rats. RN supplementation to diabetic rats significantly prevent the reduction of final body weight loss, reduced weekly fasting blood glucose levels and HbA1c levels with a significant increase in serum insulin levels. quantitative polymerase chain reaction and immunohistochemical analysis found upregulation of Nrf2, NQO-1, HO-1 and upregulation of Keap1 genes and protein distribution along with significantly reduced levels of malondialdehyde and increased activity of superoxide dismutase, catalase and glutathione peroxidase in RN-treated diabetic rats as compared to diabetic rats. Furthermore, treatment of diabetic rats with RN showed downregulated expression of tumour necrosis factor-α, matrix metalloproteinase-2 and upregulated expression of interleukin-10 (IL-10) and TIMP-1 in the retina. RN treatment decreased nuclear factor kappa-light-chain-enhancer of activated B cells distribution and increased IL-10 protein distribution in the retinae of diabetic rats. In addition, RN treatment ameliorated morphological changes observed in retinae of diabetic rats. Altogether, these results provided clear evidence that treatment of diabetic rats with RN attenuated diabetic retinal changes through its hypoglycaemic, antioxidant and anti-inflammatory effects.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Experimental; Glycated Hemoglobin; Heme Oxygenase-1; Inflammation; Male; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Rats; Rats, Wistar; Retina; Signal Transduction; Stilbenes

As a traditional natural medicine for treating many kinds of diseases,

Topics: Allopurinol; Biphenyl Compounds; Enzyme Inhibitors; Free Radical Scavengers; Gnetum; High-Throughput Screening Assays; Kinetics; Least-Squares Analysis; Picrates; Plant Extracts; Resveratrol; Stilbenes; Ultrafiltration; Xanthine Oxidase

In this work, surface magnetic molecularly imprinted polymers (SMMIPs) were synthesized and used as artificial receptors in the dispersive magnetic solid phase extraction (DMSPE) for capturing potential neuronal nitric oxide synthase-post synaptic density protein-95 (nNOS-PSD-95) uncouplers, which is known as neuroprotection against stroke. Factors that affected selective separation and adsorption of the artificial receptors, such as the amount of template, the types of functional monomer and porogen solvents, and the molar ratio of template/functional monomer/cross-linker were optimized. The artificial receptors were also characterized using fourier transformed infrared, scanning electron microscope, thermal gravimetric analysis and physical property measurement systems. Multiple interactions between template and SMMIPs led to larger binding capacities, faster binding kinetics, quicker separation abilities and more efficient selectivity than the surface magnetic nonimprinted polymers (SMNIPs). The SMMIPs were successfully applied to capture potential nNOS-PSD-95 uncouplers from complex samples, and eight compounds were seized and confirmed rapidly when combined with HPLC and MS. The detection of the new nNOS-PSD-95 uncouplers ranged from 0.001 to 1.500 mg/mL with correlation coefficients of 0.9990-0.9995. The LOD and LOQ were 0.10-0.68 μg/mL and 0.47-2.11 μg/mL, respectively. The neuroprotective effect and co-immunoprecipitation test in vitro revealed that Emodin-1-O-β-d-glucoside, Rhaponticin, Gnetol and 2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside have neuroprotective and uncoupling activities, and that they may be the new uncouplers of nNOS-PSD-95.

Topics: Animals; Cell Line, Tumor; Disks Large Homolog 4 Protein; Emodin; Glucosides; Magnetics; Molecular Imprinting; Neuroprotective Agents; Nitric Oxide Synthase Type I; PC12 Cells; Polymers; Post-Synaptic Density; Rats; Receptors, Artificial; Solid Phase Extraction; Solvents; Stilbenes

Rhaponticin (RA; 3'5-dihydroxy-4'-methoxystilbene 3-O-β-D‑glucopyranoside) is a component isolated from various medicinal herbs including Rheum undulatum L. RA has been reported to be an effective treatment for allergy, diabetes, thrombosis, liver steatosis, lung fibrosis and colitis. In addition, RA effectively inhibits tumor growth and induces apoptosis; however, the effects of RA, at non-cytotoxic doses, on the metastasis and angiogenesis of malignant cancer cells have, to be the best of our knowledge, not been identified. In the present study, it was identified that RA suppressed the metastatic potential of MDA‑MB231 breast cancer cells, including colony formation, migration and invasion. Human umbilical vein endothelial cells (HUVECs) treated with RA exhibited a decreased ability to form tube-like networks and to migrate across a Transwell membrane, when compared with RA‑untreated HUVECs. Using the chick chorioallantoic membrane assay, RA treatment significantly suppressed spontaneous and vascular endothelial growth factor (VEGF)-induced angiogenesis. Furthermore, RA inhibited the production of pro-angiogenic factors, including matrix metalloproteinase (MMP)-9, pentraxin‑3, interleukin-8, VEGF and placental growth factor under normoxic and hypoxic conditions, and suppressed the phorbol 12-myristate 13-acetate-induced increase in the gelatinolytic MMP‑9 activity and MMP‑9 expression in HT1080 cells. RA also significantly inhibited the hypoxia-inducible factor (HIF)-1α pathway, leading to decreased HIF‑1α accumulation and HIF‑1α nuclear expression under hypoxia. These results indicated that RA exhibits potent anti‑metastatic and anti‑angiogenic activities with no cytotoxicity via suppression of the HIF‑1α signaling pathway. Thus, RA may control malignant cancer cells by inhibiting the spread from primary tumors and expansion to distant organs.

Topics: Angiogenesis Inhibitors; Animals; Biological Assay; Biomarkers, Tumor; Cell Hypoxia; Cell Line, Tumor; Cell Movement; Chick Embryo; Drug Screening Assays, Antitumor; Human Umbilical Vein Endothelial Cells; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Neoplasms; Neovascularization, Pathologic; Rheum; Signal Transduction; Stilbenes; Toxicity Tests; Vascular Endothelial Growth Factor A

Pulmonary fibrosis is a scaring process related to chronic lung injury of all causes. The treatment options for pulmonary fibrosis are very limited. Rhapontin has anti-inflammatory effect and anti-proliferative activity which is widely distributed in the medicinal plants of Rheum genus in China. However, the anti-fibrotic activities of rhapontin have not been previously investigated.. The effect of rhapontin on TGF-β1-mediated extracellular matrix (ECM) deposition in primary lung fibroblast (PLF) cells, on TGF-β1 secretion in LPS-stimulated human THP-1 derived macrophages in vitro, and on bleomycin (BLM)-induced pulmonary fibrosis was investigated in vivo. Fibrotic mice were induced by intratracheal instillation of bleomycin, and then treated with rhapontin (25, 50, or 100mg/kg/day) or prednisone (6.5mg/kg/day, positive drug) for 2weeks.. In TGF-β1 stimulated PLFs, treatment with rhapontin resulted in a reduction of ECM with a decrease in Lox2 and p-Smad2/3. In LPS activated macrophages, treatment with rhapontin reduced TGF-β1 production. However, in vitro the attenuated ECM deposition and inflammatory response by rhapontin were closely associated with AMPK activation, and these suppression of rhapontin were significantly abolished by the AMPK inhibitor. Treatment with rhapontin for 2weeks resulted in an amelioration of the BLM-induced pulmonary fibrosis in rats with a lower Lox2, whereas a higher AMPK expression, with reductions of the pathological score, collagen deposition, TGF-β1, α-SMA, Lox2, and HIF-1α expressions in lung tissues at fibrotic stage at 100mg/kg.. In summary, rhapontin reversed ECM, as well as Lox2 proliferation in vitro and prevented pulmonary fibrosis in vivo by modulating AMPK activation and suppressing the TGF-β/Smad pathway.

Topics: Animals; Bleomycin; Extracellular Matrix; Fibroblasts; Humans; Lipopolysaccharides; Lung; Macrophages; Male; Medicine, Chinese Traditional; Mice; Mice, Inbred C57BL; Models, Animal; Pulmonary Fibrosis; Rheum; Signal Transduction; Smad Proteins; Stilbenes; THP-1 Cells; Transforming Growth Factor beta1

Rhapontin (3, 3', 5-trihydroxy-4'-methoxystilbene-3-O-glucoside) has anti-thrombotic, anti-allergic and anti-diabetic activities. This study aimed to assess the protective effects of rhapontin on intestinal damage in vivo and in vitro. In a dextran sodium sulfate (DSS)-induced mouse model, oral administration of rhapontin (100mg/kg) significantly attenuated colonic pathological damage and remarkably inhibited infiltration by inflammatory cells, myeloperoxidase (MPO) activity, NLRP3 inflammasome activation and SIRT1 expression in the colon. Moreover, rhapontin prevented DSS-induced impairment in the colon epithelium barrier by increasing the expression of tight junction proteins, such as zonula occludens-1(ZO-1) and occludin, and reduced apoptosis-associated protein (cyt-c, the ratio of bcl-2/bax and cleaved-capase9) expression in the colon. The in vitro results showed that rhapontin significantly reduced NLRP3 inflammasome activation and cleaved caspase-1 expression as well as lowered IL-1β secretion in LPS-stimulated human-THP-1-derived macrophages. Further study revealed that compound EX257 (an SIRT1 inhibitor) blocked the inhibitory effects of rhapontin on NLRP3-dependent caspase-1 activation and IL-β production in activated macrophages. In addition, in TNF-α-stimulated intestinal epithelial NCM460 cells, rhapontin significantly increased the expressions of occludin and ZO-1 and notably reduced the ratio of bcl-2/bax and cleaved-capase9 expression through SRIT1 signaling. In sum, the protective effect of rhapontin is from blocking the NLRP3 priming cascade reaction and is dependent on SIRT1 activation. Our findings demonstrate that rhapontin might be a potential agent for the treatment of colitis by targeting SIRT1.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Cell Line; Colitis; Colon; Dextran Sulfate; Epithelial Cells; Female; Humans; Mice; Mice, Inbred BALB C; Models, Animal; NLR Family, Pyrin Domain-Containing 3 Protein; Signal Transduction; Sirtuin 1; Stilbenes; Transcriptional Activation

High efficiency and less solvent consumption are the essential requirements of high-speed countercurrent chromatography (HSCCC), especially for the large-scale preparation. In this study, an efficient HSCCC strategy with consecutive sample injection was successfully developed to rapidly separate and purify rhaponticin and rhapontigenin from the seeds of the Chinese medicinal herb fenugreek (Trigonella foenum-graecum L.). The effective separation was achieved using n-hexane-ethyl acetate-methanol-water (1:4:2:6, v/v/v/v) as the two-phase solvent system, in which the mobile phase was eluted at an optimized flow rate of 2.2 mL/min and a revolution speed of 850 rpm. After consecutively loading four identical fenugreek samples, each containing 120 mg, HSCCC separation yielded 146.4 mg of rhaponticin and 174.8 mg of rhapontigenin with purities of 98.6 and 99.1%, respectively, as determined by high-performance liquid chromatography at 320 nm. Their chemical structures were identified using UV spectroscopy, (1)H-NMR and (13)C-NMR. The HSCCC method with consecutive sample injection allowed faster separation and produced less solvent waste, suggesting that it is an efficient way to rapidly separate and purify natural products on a large scale.

Topics: Acetates; Chromatography, High Pressure Liquid; Countercurrent Distribution; Flow Injection Analysis; Hexanes; Liquid-Liquid Extraction; Methanol; Plant Extracts; Seeds; Solvents; Stilbenes; Trigonella; Water

A specific and reliable ultra-performance liquid chromatography-diode array detection method has been developed and validated for the quantitative assessment of a traditional Oriental herbal formulation, Samhwangsasim-tang (SST). A Halo reversed-phase amide column (2.7 µm, 4.6 × 150 mm) was used to separate marker compounds; detection was conducted by ultraviolet absorbance at 250 nm. The column temperature was maintained at 45°C. A mobile phase consisting of acetonitrile (A) and 0.1% trifluoroacetic acid in water (B) was found to be suitable for the separation, at a flow rate of 1.8 mL/min with gradient elution. Linearity, specificity, precision and recovery were calculated to validate the method and instrumentation. Under the described conditions, all marker compounds (rhaponticin, berberine, palmatine, baicalin, baicalein and wogonin) were collected within 25 min. All calibration curves of components showed good linearity (correlation coefficient > 0.9996). The limit of detection and limit of quantification ranged from 0.08-3.05 and 0.23-8.12 µg/mL, respectively. The relative standard deviation (RSD) and repeatability values of intra-day and inter-day precision were less than 2.30, 2.99 and 1.82%, respectively. In the recovery test, the accuracy ranged from 97.56-103.30% with RSD values less than 2.63%. The developed method was simple, specific, sensitive, accurate, precise and reproducible for the quantification of the active chemical constituents of SST. The simultaneous analysis of the contents of marker compounds in different SST samples prepared by different extraction procedures and different commercial products was successfully evaluated.

Topics: Berberine Alkaloids; Chromatography, High Pressure Liquid; Drugs, Chinese Herbal; Flavonoids; Limit of Detection; Linear Models; Reproducibility of Results; Sensitivity and Specificity; Stilbenes

Fatty acid synthase (FAS) has attracted more and more attention as a potential target for cancer treatment. Natural FAS inhibitors are emerging as potential therapeutic agents to treat cancer. Rheum tanguticum Maxim. ex Balf. (rhubarb) is a traditional Chinese nutritional food and has been reported to possess a variety of biological activities, including the ability to induce the apoptosis of cancer cells. This study indicates that desoxyrhaponticin (DC) and rhaponticin (RC), two stilbene glycosides from rhubarb, could be considered as promising FAS inhibitors. We found that both DC and RC could inhibit intracellular FAS activity and downregulate FAS expression in human breast cancer MCF-7 cells. In addition, the apoptotic effect of DC on human cancer cells was announced for the first time. Since FAS plays a key role in the biosynthesis pathway of fatty acids in cancer cells, these findings suggest that DC has potential applications in the prevention and treatment of cancer.

Topics: Apoptosis; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Down-Regulation; Enzyme Inhibitors; Fatty Acid Synthases; Fatty Acids; Female; Glucosides; Humans; Plant Extracts; Rheum; Stilbenes; Tibet

Rhapontin was purified from a methanol extract from the roots of Rheum undulatum, and rhapontigenin was produced by an enzymatic transformation of rhapontin. Rats were fed a high-cholesterol diet to induce hyperlipidemia, followed by oral treatment with rhapontin or rhapontigenin (1-5 mg/kg/day). Rhapontin and rhapontigenin treatment resulted in a significant (p<0.05) dose-dependent decrease in the serum lipid level, while the high-density lipoprotein cholesterol level increased slightly compared with the experimental control. Furthermore, rhapontin and rhapontigenin treatment improved the pathological characteristics of the degenerating fatty liver in high-cholesterol diet-induced hyperlipidemic rats dose-dependently. Aspartate aminotransferase and alanine aminotransferase levels in rhapontin- and rhapontigenin-treated hyperlipidemic rats were not significantly different from those in the control. These results indicate that rhapontin and rhapontigenin can be used as potent antihyperlipidemic agents.

Topics: Animals; Cholesterol; Fatty Liver; Hyperlipidemias; Hypolipidemic Agents; Plant Extracts; Rats; Rats, Sprague-Dawley; Rheum; Stilbenes; Triglycerides

To prepare beta-cyclodextrin (beta-CD)-deoxyrhaponti inclusion complex by the homogeneous method, and characterize the inclusion complex with ultraviolet-visible spectrum and fluorescence spectroscopy, in order to determine the inclusion rate, the ratio of subject-object, the binding constant of supra-molecular system and the thermodynamic function. The results showed that the designed method was so rational that the inclusion complex was successfully prepared. The ultraviolet-visible spectrophotometry method was adoptedto determine the inclusion rate of 38%, and the ratio of subject-object of 2: 1. The thermodynamic parameters of this inclusion complex: deltaH(0), deltaS(0) was all smaller than zero, which indicated that the main acting forces generated by the inclusion complex were hydrogen bonding and Vander Waals' force. deltaG(0) < 0 and deltaG(0) were directly proportional to the reaction temperature, which suggested that the reaction would spontaneously increase with the temperature rise. The polarization fluorescence method was used to quantitatively prove the non-covalent inclusion complex generated during the interaction between beta-CD interacting with DES. The results could also provide reference for studies on cyclodextrin supra-molecular system.

Topics: beta-Cyclodextrins; Drug Carriers; Drugs, Chinese Herbal; Nanoparticles; Stilbenes

Rhapontigenin, an aglycone of rhapontin, was produced by biotransformation and we investigated its antifungal activity against Candida albicans, one of the most important opportunistic fungal pathogens. Rhapontigenin is found to have, in vitro, inhibitory activity with a minimal inhibitory concentration (MIC) value against all test isolates of 128-256 μg/ml. We detected increased reactive oxygen species (ROS) levels in yeast cultures treated with rhapontigenin at the MIC. Rhapontigenin inhibited DNA, RNA, and protein synthesis, especially RNA synthesis, and induced morphological changes and apoptosis of C. albicans. The apoptotic effect of rhapontigenin on C. albicans at subinhibitory concentrations was higher in the stationary growth phase than in the exponential phase, while the opposite results were noted with amphotericin B. The mechanism of antifungal activity of rhapontigenin may be associated with the generation of ROS that might induce apoptosis and it may also involve the inhibition of ergosterol biosynthesis.

Topics: Antifungal Agents; Apoptosis; Candida albicans; Candidiasis; Drug Resistance, Fungal; Ergosterol; Flow Cytometry; Microbial Sensitivity Tests; Protoplasts; Reactive Oxygen Species; Stilbenes

To improve the therapeutic effect of rhaponticin (RHA), a folate receptor (FR) targeted RHA conjugate was synthesized by utilizing a hydrophilic peptide spacer linked to folic acid (FA) via a releasable disulfide linker. This water-soluble conjugate was found to retain high affinity for FR-positive cells, and it produced specific, dose-responsive activity in vitro. Treatment of FRHA with a reducing agent indicated that the amino-reactive derivative of RHA would be released spontaneously following disulfide bond reduction within the endosomes. FRHA also proved to be active predominantly specific against FR-positive syngeneic and xenograft models in vivo, and possible curative activity resulted with minimal to moderate toxicity. The FRHA conjugate greatly enhanced the therapeutic effects and reduced the toxicity of RHA. In conclusion, FRHA represents a folate-targeted chemotherapeutic that can produce potent activity against established sc tumors. Hence, this report has a great significance in pharmacology and clinical medicine as well as methodology.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Folate Receptors, GPI-Anchored; Folic Acid; Humans; Mice; Mice, Inbred BALB C; Neoplasms; Stilbenes

Rhaponticin (RH) possesses a variety of pharmacological activities including potent antitumor, antitumor-promoting, antithrombotic, antioxidant and vasorelaxant effects. The fundamental photophysics of RH is not well understood. In this work, solvent effect on the photoluminescence behavior of RH was studied by fluorescence and absorption spectra. The bathchromic shift was observed in absorption and fluorescence spectra with the increase of solvents polarity, which implied that transition involved was π→π. A quantitative estimation of the contribution from different solvatochromic parameters, like normalized transition energy value (E(T)(N)), was made using the linear stokes shift (Δν) relationship based on the Lippert-Suppan equation. The ground state and excited state dipole moments were calculated by quantum-mechanical second-order perturbation method as a function of the dielectric constant (ε) and refractive index (n). The result was found to be 2.23 and 3.67D in ground state and excited state respectively. The density functional theory (DFT) was used to obtain the most stable structure, electronic excitation energy, dipole moments and charge distribution. The analysis revealed that the RH exhibited strong photoinduced intramolecular charge transfer (ICT), and the intermolecular hydrogen bonding ability of the solvent was the most important parameter to characterize the photophysics behavior of RH. The hydrogen bonding effect occurred at the localized electron-acceptor oxygen at the glycoside bond. The experimental and theoretical results would help us better understand the photophysical properties of RH.

Topics: Antineoplastic Agents; Antioxidants; Fibrinolytic Agents; Luminescence; Models, Molecular; Quantum Theory; Rheum; Solvents; Spectrometry, Fluorescence; Spectrophotometry; Stilbenes; Vasodilator Agents

Rhaponticin (RA) extracted from many medicinal plants has been demonstrated to possess a variety of pharmacological activities including potent antitumor, antitumor-promoting, antithrombotic, antioxidant and vasorelaxant activities. However, its poor solubility and bioavailability restricted the clinical application greatly. In this work, surface modification of liposome with polyethylene glycol (PEG) was developed with the purpose of improving the pharmacokinetics and anti-tumor efficacy of RA. PEGylated liposomal RA (PEGL-RA) was prepared by dry-film method. Its mean particle size was 89.3 +/- 8.7 nm, mean zeta potential was -4.1 mV and encapsulation efficiency was 67.4 +/- 6.4%. Moreover, the results of pharmacokinetic analysis showed that the time of maximum plasma concentration (Tmax) of PEGL-RA was about 4.5 times higher than that of free RA after oral administration due to the lower distribution into the gastrointestinal tract. The mean T1/2 value of PEGL-RA and free RA were 350.12 +/- 0.87 min and 180.02 +/- 1.96 min, respectively. The AUC0-->infinity ratio of PEGL-RA to free RA was about 2.41-fold (93.23 microg/mLmin/40.81 microg/mLmin). Plasma protein binding ability of RA was also studied. The results showed that RA with 33.6 microg/mL concentrations in human plasma and HSA achieved the percent of bound 39.23 +/- 3.78% and 22.28 +/- 2.34%, respectively. In the in vivo studies utilizing solid tumor-bearing rat, it was confirmed that PEGL-RA delivered remarkably larger amount of RA to tumor tissue and provided more significant anti-tumor activity than free RA. Furthermore, the cytotoxicity and fluorescence microscopic studies showed higher intracellular uptake of PEGL-RA than that of RA. In conclusion, PEGylated liposome was an effective delivery formulation for RA to increase the pharmacokinetics and therapeutic efficacy.

Topics: Animals; Antineoplastic Agents; Area Under Curve; Drug Screening Assays, Antitumor; Female; Half-Life; Humans; Liposomes; MCF-7 Cells; Mice; Mice, Nude; Microscopy, Electron, Transmission; Microscopy, Fluorescence; Polyethylene Glycols; Rats; Stilbenes

Rhaponticin (RHA) possesses a variety of pharmacological activities including potent antitumor, antitumor-promoting, antithrombotic, antioxidant and vasorelaxant effects. In the solvation effect, RHA exhibited bathochromic shift in emission spectra with the increasing solvent polarity. The binding between RHA and HSA was investigated by molecular spectroscopy combining with modeling and equilibrium dialysis. Fluorescence data showed that the quenching of HSA by RHA was result of forming the complex of RHA-HSA. According to Stern-Volmer equation, the binding parameters between RHA and HSA were determined. The enthalpy change (ΔH) and entropy change (ΔS) were calculated to be -2.75kJmol(-1) and 1.58Jmol(-1)K(-1), indicating that the hydrogen bonds and hydrophobic interactions played a dominant role in the binding. The conformational investigation revealed the α-helical structure was decreased and the polypeptides of HSA were slightly folded upon the addition of RHA. The effect of common ions on the binding between RHA and HSA was also investigated. Furthermore, the result of warfarin displacement site indicated that RHA could bind to the site I of HSA, which was in agreement with the molecular modeling. When excitation wavelength was set at 260 or 355nm, RHA exhibited a fluorescence peak at 390nm, based on which, a simple and rapid fluorimetric method was developed and validated to determine RHA in the equilibrium dialysis. Calibration curves of RHA were linear over the concentration range of 1.1-15.0μM with the detection limits of 0.03μM. Examination of protein binding ability showed that RHA with 8.0μM concentrations in HSA achieved the percent of bound 82.3±2.5%.

Topics: Antineoplastic Agents; Antioxidants; Fibrinolytic Agents; Humans; Hydrogen Bonding; Models, Molecular; Protein Binding; Serum Albumin; Spectrometry, Fluorescence; Stilbenes; Thermodynamics

Rhaponticin (Rheum L.) demonstrates a variety of pharmacological activities, including antitumor, antithrombotic and antioxidant effect. However, there is no information describing the pharmacokinetics, bioavailability and metabolism of rhaponticin after intravenous administration.. UHPLC-Q-TOF/MS and UHPLC-multistage tandem MS methods were developed for the pharmacokinetics, bioavailability and metabolism of rhaponticin in rats. The metabolite of rhaponticin, rhapontigenin, a potent inhibitor of cytochrome P450, was confirmed by UHPLC-multistage tandem MS. The plasma profile of rhaponticin and rhapontigenin was determined by UHPLC-Q-TOF/MS. The results showed that rhaponticin was rapidly distributed and eliminated from rat plasma. The absolute oral bioavailability of rhaponticin was calculated to be 0.03%. The plasma concentrations of rhapontigenin rapidly increased and gradually eliminated after intravenous administration.. The present pharmacokinetics, bioavailability and metabolism studies of rhaponticin will provide helpful information for development of suitable dosage forms and clinical references on rational administration.

Topics: Administration, Oral; Animals; Area Under Curve; Biological Availability; Chromatography, High Pressure Liquid; Drug Stability; Mass Spectrometry; Rats; Stilbenes

The magnetic molecularly imprinted polymers (MMIPs) had been synthesized for the selective extraction and clean-up of rhaponticin in Chinese patent medicines (CPM). The MMIPs were prepared via suspension polymerization, using Fe(3)O(4) as magnetically component, rhaponticin as template molecule, acrylamide (AM) as functional monomers, styrene (St) as copolymer monomer and ethylene glycol dimethacrylate (EGDMA) as a cross-linker in dimethyl sulfoxide porogen. The obtained MMIPs were characterized using scanning electron microscopy (SEM) and Fourier transform infrared (FT-IR), X-ray diffraction (XRD) and vibrating sample magnetometer (VSM). High performance liquid chromatography (HPLC) was used for analysis the target analytes. The polymers were evaluated further by batch rebinding experiments. From the derived Freundlich isotherm (FI) equation their binding capacity and binding strength were determined. Structurally similar compound resveratrol and a reference compound kirenol were used for investing the selective recognition capability of MMIPs. The MMIPs were used as sorbents for selective pre-concentration of rhaponticin from CPM samples. The contents of rhaponticin for the four CPM samples were found to be 11.84, 3.35, 4.47, and 7.57μg g(-1), respectively, and the recoveries of spiked samples ranged from 77.82% to 91.00%. The prepared MMIPs could be applied to selectively pre-concentrate and determine rhaponticin in CPM samples.

Topics: Adsorption; Drugs, Chinese Herbal; Magnetite Nanoparticles; Molecular Imprinting; Spectroscopy, Fourier Transform Infrared; Stilbenes

Rhapontigenin was produced from rhapontin isolated from a methanol extract of Rheum undulatum roots by enzymatic transformation. Rhapontin and rhapontigenin exhibited dose-dependent inhibition of tyrosinase activity and melanin synthesis in B16F10 melanoma cells, but the inhibitory activity of rhapontigenin was greater than that of rhapontin. Thus the bioconversion of rhapontin enhanced its ability to inhibit cellular tyrosinase activity and melanin synthesis.

Topics: Animals; Biotransformation; Cell Line, Tumor; Melanins; Mice; Rheum; Stilbenes

The light-induced cis-trans isomerization of rhapontigenin (RHA) and its glucoside rhaponticin (RHA-Glc) were evaluated under ultraviolet (UV) light irradiation. A simple and rapid capillary electrophoresis method was developed for the kinetic study of four stilbenes (both cis and trans form of RHA and RHA-Glc). These analyses were achieved by using β-cyclodextrin (β-CD) modified capillary zone electrophoresis with diode array detector (CZE-DAD). The method provided reliable separations with a short analysis time of 3 min. The purity of individual compound was checked by UV spectral comparisons with known standards, and further confirmed by (1)H and (13)C nuclear magnetic resonance (NMR) spectroscopy. Furthermore, the UV absorbance and the molar absoptivity (ε) values were determined by UV-vis spectrophotometer to be 36824 L mol(-1) cm(-1) at λ(max) 324.5 nm for trans-RHA and 43894 L mol(-1) cm(-1) at λ(max) 325 nm for trans-RHA-Glc in methanol/water mixture solution (50%, v:v), respectively. CZE, UV-vis and NMR spectroscopy studies provided similar conclusions by considering the influence of irradiation time and the influence of irradiation wavelength.

Topics: Electrophoresis, Capillary; Molecular Structure; Spectrophotometry, Ultraviolet; Stereoisomerism; Stilbenes; Ultraviolet Rays

The interaction mechanism between rhaponticin (RT) and human serum albumin (HSA) has been studied by fluorescence spectroscopy and absorbance spectra. The mediation effect that the metal ions took part in the interaction has also been discussed in this paper. Based on different theoretical models of fluorescence quenching, the binding constant (K) and binding sites (n) of the interaction were determined and analyzed comparatively. The quenching mechanism of the binding reaction has also been discussed. The binding distance (r) and energy-transfer efficiency (E) between RT/RT-Co(II)/RT-Ni(II) and HSA were also obtained by virtue of the Förster theory of non-radiation energy transfer. The effect of RT acting on the HSA's conformation was analyzed by synchronous fluorescence spectroscopy. The result showed that the result calculated by different theoretical models is generally equivalent and RT bound HSA strongly by forming stable complex, which indicates that HSA under physiological conditions can act as a carrier for RT to be transported to exert effects. The microconformation of HSA changed significantly due to hydrophobicity change in the chemical environment of some fluorescence chromophores in the subdomain IIA and IIB of HSA. Metal ions Co(II) and Ni(II) can mediate RT-HSA interaction, making the binding of the drug to protein stronger, which indicates that Co(II) and Ni(II) can enhance rhaponticin's medical efficacy under physiological conditions.

Topics: Binding Sites; Drug Interactions; Energy Transfer; Humans; Hydrophobic and Hydrophilic Interactions; Ions; Metals; Models, Molecular; Protein Binding; Protein Conformation; Serum Albumin; Spectrometry, Fluorescence; Spectrophotometry, Ultraviolet; Stilbenes

Biotransformation is often used to improve chemical activity. We evaluated the antimicrobial activity of rhapontigenin, converted from rhapontin after treatment with Pectinex. Rhapontigenin showed 4-16 times higher antimicrobial activity than rhapontin. Activity was higher against Gram positive strains than Gram negative strains. Minimum inhibitory concentrations (MICs) of rhapontigenin, retinol, and five antibiotics were determined by microbroth dilution method for antibiotic-sensitive and -resistant Propionibacterium acnes. We also investigated the in vitro antibacterial activity of rhapontigenin in combination with antibiotic against antibiotic-resistant P. acnes. The antibiotic combination effect against resistant P. acnes was studied by checkerboard method. The combination formulations (rhapontigenin and clindamycin, retinol and clindamycin) showed synergic effects on the inhibition of the growth of clindamycin-resistant P. acnes. It is predictable that the combination of antibiotics with rhapontigenin is helpful to treat acne caused by antibiotic resistant P. acnes. The antibacterial activity of rhapontigenin was enhanced by biotransformation.

Topics: Anti-Bacterial Agents; Plant Extracts; Propionibacterium acnes; Rheum; Stilbenes

We isolated several stilbene compounds including rhaponticin (3',5-dihydroxy-4'-methoxystilbene 3- O-beta- D-glucopyranoside) from extracts of rhubarb rhizomes. These compounds showed significant hypoglycemic effects in streptozotocin (STZ)-induced type 1 diabetic rats and mice. In this study, we investigated the effect of rhaponticin on glucose utilization, lipid metabolism, and liver and heart function in a KK/Ay type 2 diabetic mouse model. The results showed that oral administration of rhaponticin (125 mg/kg) significantly reduced blood glucose levels and improved oral glucose tolerance of KK/Ay diabetic mice. Elevated plasma triglyceride (TG), low density lipoprotein (LDL), cholesterol (CHO), non-esterified free fatty acids (NEFA), and insulin levels were also markedly attenuated. Serum enzymatic activities of lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) in the rhaponticin-treated group significantly decreased in comparison to the untreated model group. Livers of rhaponticin-treated mice had relatively normal cellular size and decreased fibrosis and steatosis. In addition, rhaponticin administration caused a remarkable increase in the hepatic glycogen content and a significant reduction in the hepatic triglyceride content. These results indicate that rhaponticin has a noticeable antidiabetic effect and could be potentially used as a new agent to treat type 2 diabetes mellitus and its complications.

Topics: Animals; Blood Glucose; Cholesterol; Diabetes Mellitus, Experimental; Enzymes; Fatty Acids, Nonesterified; Fatty Liver; Glucose Tolerance Test; Glycogen; Hypoglycemic Agents; Insulin; Lipids; Lipoproteins, LDL; Liver; Mice; Rheum; Rhizome; Stilbenes; Triglycerides

It is known that cyclodextrins (CDs) extract lipid components from bilayer of liposomes. This could undermine the potential benefits of liposomes as drug carriers. In this study, we demonstrated that PC-Chol liposomes with various CDs or rhapontin (Rh)-hydroxypropyl betaCD (HPbetaCD) complexes could be stabilized by association with the amphiphilic polyelectrolyte, poly(methacrylic acid-co-stearyl methacrylate). Based on the results of differential scanning calorimetry, photocorrelation spectroscopy and transmission electron microscopy, the polymer-associated liposomes had the same vesicular form as liposome with clear boundaries and retained structural integrity for at least 1 month. In addition, the polymer-associated structure was unaffected by the type of CD, the composition and concentration of lipid components, and the concentration of the Rh-HPbetaCD complex. This contrasted with PC-Chol liposomes, whose structure was dependent on these factors. Using structurally different polymer-associated liposomes and PC-Chol liposomes containing the Rh-HPbetaCD complex, we also showed that the stability of vesicles could influence the skin permeability of CD-drug complexes.

Topics: Cyclodextrins; Lipid Bilayers; Liposomes; Methacrylates; Particle Size; Stilbenes

Rhubarb extracts have been reported to improve oral glucose tolerance in diabetic animals. In the present study we have investigated the antidiabetic actions of desoxyrhaponticin, a major stilbene in rhubarb, as a glucose uptake inhibitor. Desoxyrhaponticin was demonstrated to inhibit glucose uptake in rabbit intestinal membrane vesicles as well as in rat everted gut sleeves, with IC50 values of 148.3 and 30.9 microM, respectively. Kinetics studies revealed that desoxyrhaponticin is a competitive inhibitor of glucose uptake in both systems. Moreover, desoxyrhaponticin could reduce glucose uptake in the intestinal membrane vesicles of both normal and diabetic rats. In addition, glucose uptake in the renal membrane vesicles of both normal and diabetic rats was reduced by desoxyrhaponticin. Under the inhibition of desoxyrhaponticin, uptake of glucose in both the intestinal and renal membrane vesicles of the normal rats was no different from that of the diabetic rats. The IC50 values of the uptake inhibition in the renal membrane vesicles of normal and diabetic rats were 118.8 and 115.7 microM, respectively. In a type 2 diabetic animal model in which rats have been treated with streptozotocin at the neonatal stage, postprandial hyperglycemia was significantly suppressed by oral administration of this compound (300 mg/kg b.wt.). These results suggest that desoxyrhaponticin is an agent that is potentially effective in controlling postprandial hyperglycemia in diabetes. The in vivo antidiabetic action of this compound can be explained, in part at least, by inhibition of glucose transport in the small intestine and inhibition of glucose reabsorption in the kidney.

Topics: Animals; Biological Transport; Diabetes Mellitus, Experimental; Glucose; Glucosides; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Intestinal Mucosa; Kidney; Microvilli; Rabbits; Rats; Rats, Wistar; Stilbenes

We have investigated the effects of rhapontin on proliferation and DNA of human stomach cancer KATO III cells. Growth inhibition and induction of apoptosis by rhapontin were observed in the KATO III cells. Morphological change showing apoptotic bodies was observed in the KATO III cells treated with rhapontin. The fragmentation of DNA by rhapontin to oligonucleosomal-sized fragments that is a characteristic of apoptosis was observed to be concentration- and time-dependent in the KATO III cells. N-acetyl-L-cysteine, an antioxidant, suppressed the DNA fragmentation caused by rhapontin. On the other hand, it was found that resveratrol having stilbene moiety as well as rhapontin induced apoptosis in the KATO III cells. So, it is considered that stilbene moiety in the molecule is essential for the induction of apoptosis. The data of the present study show that the suppression of KATO III cell-growth by rhapontin results from the induction of apoptosis by the compound, and that active oxygen is involved in the inductions of apoptosis caused by rhapontin in the KATO III cells.

Topics: Acetylcysteine; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Line, Tumor; DNA Fragmentation; Dose-Response Relationship, Drug; Electrophoresis, Agar Gel; Free Radical Scavengers; Humans; Molecular Structure; Resveratrol; Rheum; Stilbenes; Time Factors

There is increasing interest in the study of the antioxidant actions of plant phenolic compounds as evidence shows that consumption of plant products rich in these compounds contributes to protection from a number of ailments including cardiovascular diseases. In the present study, the antioxidant effects of selected phenolic compounds from dietary sources, namely barbaloin, 6-gingerol and rhapontin, were investigated.. Low-density lipoprotein (LDL), erythrocytes and erythrocyte membranes were subjected to several in vitro oxidative systems. The antioxidant effects of the phenolic compounds were assessed by their abilities in inhibiting hemolysis and lipid peroxidation of LDL and erythrocyte membranes, and in protecting ATPase activities and protein sulfhydryl groups of erythrocyte membranes.. 6-Gingerol and rhapontin were found to exhibit strong inhibition against lipid peroxidation in LDL induced by 2,2'-azobis(2-amidinopropane) hydrochloride (AAPH) and hemin while barbaloin possessed weaker effects. A similar order of antioxidant potencies among the three compounds was observed on the lipid peroxidation of erythrocyte membranes in a tert-butylhydroperoxide (tBHP)/hemin oxidation system. On the other hand, barbaloin and rhapontin were comparatively stronger antioxidants than 6-gingerol in preventing AAPH-induced hemolysis of erythrocytes. Among the three compounds, only barbaloin protected Ca2+-ATPase and protein sulfhydryl groups on erythrocyte membranes against oxidative attack by tBHP/hemin. Interestingly, rhapontin demonstrated protective actions on Na+/K+-ATPase in a sulfhydryl group-independent manner under the same experimental conditions.. In view of their protective effects on LDL and erythrocytes against oxidative damage, these phenolic compounds might have potential applications in prooxidant state-related cardiovascular disorders.

Topics: Amidines; Animals; Anthracenes; Antioxidants; Cardiovascular Diseases; Catechols; Cells, Cultured; DNA Damage; Dose-Response Relationship, Drug; Erythrocyte Membrane; Fatty Alcohols; Hemolysis; Humans; Lipid Peroxidation; Lipoproteins, LDL; Male; Oxidation-Reduction; Phenols; Rats; Rats, Sprague-Dawley; Stilbenes

Extracts from Rhei Rhizoma extracts (RR) have been reported to attenuate metabolic disorders such as diabetic nephropathy, hypercholesterolemia and platelet aggregation. With this study we investigated the anti-diabetic action of 70% ethanol RR extract in streptozotocin-induced diabetic mice, and determined the action mechanism of active compounds of RR in vitro. In the diabetic mice, serum glucose levels at fasting and post-prandial states and glucose area under the curve at modified oral glucose tolerance tests were lowered without altering serum insulin levels, indicating that RR contained potential anti-diabetic agents. The fractions fractionated from RR extracts by XAD-4 column revealed that 60%, 80% and 100% methanol fractions enhanced insulin sensitivity and inhibited alpha-glucoamylase activity. The major compounds of these fractions were sennosides, rhein and rhaponticin. Rhaponticin and rhein enhanced insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Rhaponticin increased adipocytes with a differentiating effect similar to pioglitazone, but rhein and sennoside B decreased triglyceride accumulation. Sennoside A and B inhibited alpha-glucoamylase activity as much as acarbose. In conclusion, a crude extract of RR improves glucose intolerance by enhancing insulin-stimulated glucose uptake and decreasing carbohydrate digestion via inhibiting alpha-glucoamylase activity. Rhein and rhaponticin are potential candidates for hypoglycemic agents.

Topics: Adipocytes; Animals; Anthraquinones; Blood Pressure; Body Weight; Cell Differentiation; Cell Line; Diabetes Mellitus, Experimental; Enzyme Inhibitors; Ethanol; Fibroblasts; Glucan 1,4-alpha-Glucosidase; Hypoglycemic Agents; Insulin; Insulin Resistance; Male; Mice; Mice, Inbred C57BL; Plant Extracts; Senna Extract; Sennosides; Solvents; Stilbenes; Triglycerides

Amyloid beta (1-42) peptide is considered responsible for the formation of senile plaques that accumulate in the brains of patients with Alzheimer's disease (AD). In the last years considerable attention has been focused on identifying natural food products, such as phytochemicals that prevent or almost retard the appearance of amyloid beta (1-42)-related neurotoxic effects. In this study, human neuroblastoma cells (IMR-32) was used as system model to evaluate the protective role of rhaponticin (3,3',5-trihydroxy-4'-methoxystilbene 3-O-d-glucoside) a stilbene glucoside extracted from rhubarb roots (Rhei rhizoma) and rhapontigenin, its aglycone metabolite, against amyloid beta (1-42)-dependent toxicity. The obtained results show that rhapontigenin maintains significant cell viability in a dose-dependent manner and it exerts a protective effect on mitochondrial functionality, as evidenced by mitochondrial oxygen consumption experiments. A similar behaviour, but to a lesser extent, has been shown by rhaponticin. The protective mechanism mediated by the two stilbenes could be related to their effect on bcl-2 gene family expression. Bax, a pro-apoptotic gene, resulted down-regulated by the treatment with rhaponticin and rhapontigenin compared with the results obtained in the presence of amyloid beta (1-42) peptide. Conversely, bcl-2, an anti-apoptotic gene, highly down-regulated by amyloid beta (1-42) treatment, resulted expressed in the presence of stilbenes similarly to that shown by control cells. The obtained results support the hypothesis that amyloid beta (1-42)-induced neurotoxicity occurs via bax over-expression, bcl-2 down-regulation, firstly indicating that rhaponticin and its aglycone moiety may alter this cell death pathway. Based on these studies, we suggest that rhaponticin and its main metabolite could be developed as agents for the management of AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Apoptosis Regulatory Proteins; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Humans; Mitochondria; Nerve Degeneration; Neuroprotective Agents; Oxygen Consumption; Peptide Fragments; Plant Extracts; Plaque, Amyloid; Rheum; Signal Transduction; Stilbenes

To evaluate the antithrombotic and antiallergic properties of rhaponticin extracted from Rhei Rhizoma, the in vitro and ex vivo inhibitory activities of rhaponticin and its metabolite, rhapontigenin, were measured. These compounds inhibited in vitro ADP- and collagen-induced platelet aggregation. Rhapontigenin was more potent, with IC50 values of 4 and 70 microg/ml, respectively. In ex vivo ADP- and collagen-induced rat platelet aggregation, these compounds also exhibited a potent inhibitory effect. The antiplatelet aggregation effects of rhaponticin and rhapontigenin were more potent than those of aspirin. Rhapontigenin showed significant protection from death due to pulmonary thrombosis in mice. Rhapontigenin also showed the strongest inhibitory activity against beta-hexosaminidase release induced by DNP-BSA. These compounds inhibited PCA reaction in mice. Rhapontigenin intraperitoneally administered showed the strongest inhibitory activity and significantly inhibited PCA at doses of 25 and 50 mg/kg, with inhibitory activities of 48 and 85%, respectively. The inhibitory activity of orally administered rhaponticin was stronger than that of intraperitoneally administered rhaponticin. These results suggest that rhaponticin, in the rhizome of Rhei Rhizoma, is a prodrug that has extensive antiallergic and antithrombotic properties.

Topics: Animals; Anti-Allergic Agents; Antioxidants; Bacteria; beta-N-Acetylhexosaminidases; Biotransformation; Blood Coagulation; Blood Platelets; Cell Line; Enzyme Inhibitors; Fibrinolytic Agents; Humans; Hyaluronoglucosaminidase; In Vitro Techniques; Intestines; Male; Mice; Passive Cutaneous Anaphylaxis; Platelet Aggregation; Rats; Rats, Sprague-Dawley; Rheum; Stilbenes

To determine six effective components (aloe-emodin, rhein, emodin, rhaponticin, physcion and chrysophanol) in Rheum.. Using buffer solution containing 20 mmol.L-1 borax, 20 mmol.L-1 sodium deoxycholate (SDC), 20 mmol.L-1 sodium taurocholate (STC), 15 mmol.L-1 beta-cyclodextrin (beta-CD) and O-phthalic acid as the internal standard, the six components were determined by cyclodextrin modified micellar electrokinetic chromatography.. In less than 25 min, aloe-emodin, rhein, emodin, rhaponticin, physion and chrysophanol were separated. The separation conditions were optimized by adjusting buffer pH, concentrations of SDC, STC and beta-CD. The linearity ranges of aloe-emodin, rhein, emodin, rhaponticin, physcion and chrysophanol were 4-34, 5-40, 4-60, 5-80, 6-90 and 5-85 micrograms.mL-1 respectively. Relative standard deviation (RSD) of the method was less than 2.2%. The recoveries of aloe-emodin, rhein, emodin, rhaponticin, physcion and chrysophanol were 100.0%, 98.3%, 100.4%, 94.6%. 95.2% and 93.8% respectively. Raw Rheum, Mongolian Rheum and Rheum tanguticum samples were analyzed.. This method can be an effective one for identification of Rhubarb.

Topics: Anthraquinones; Chromatography, Micellar Electrokinetic Capillary; Cyclodextrins; Emodin; Plants, Medicinal; Quality Control; Rheum; Stilbenes

To study the chemical constituents of Rhaponticum uniflorum.. Solvent extraction, separation by silica gel column chromatography and identification by physico-chemical properties and spectral data.. A new ecdysone hormone, rhaponticum (1) was isolated from the root of R. uniflorum together with a known compound ecdysterone(2).. The two compounds were obtained from the plant for the first time.

Topics: Asteraceae; Ecdysterone; Molecular Structure; Plant Roots; Plants, Medicinal; Stilbenes

Rhaponticin and chrysophanol 8-o-beta-D-glucopyranoside isolated from the rhizomes of Rheum undulatum (Family Polygonaceae) are metabolized to rhapontigenin and chrysophanol, respectively, by human intestinal microflora. Most intestinal bacteria isolated from human feces catalyzed these metabolic pathways. Among rhaponticin and chrysophanol 8-o-beta-D-glucopyranoside and their metabolites, rhapontigenin had the most potent inhibitory activity on a hyaluronidase, a histamine release from mast cell and passive cutaneous anaphylaxis (PCA) PCA reaction. The inhibitory activity of rhapontigenin was more potent than that of disodium cromoglycate, one of the commercial anti-allergic drugs. These results suggest that rhaponticin in the rhizomes of R. undulatum is a prodrug that has an extensive anti-allergic property.

Topics: Animals; Anthraquinones; Anti-Allergic Agents; Bacteria; Glucosides; Guinea Pigs; Histamine; Hyaluronoglucosaminidase; Intestines; Male; Mast Cells; Mice; Mice, Inbred ICR; Passive Cutaneous Anaphylaxis; Peritoneal Cavity; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Rheum; Stilbenes

Topics: Animals; Cyclooxygenase Inhibitors; Male; Plant Extracts; Prostaglandin-Endoperoxide Synthases; Resveratrol; Seminal Vesicles; Sheep; Stilbenes

The contents of rhapontin in the root of Rheum hotaoense were determined by CS-920 TLC-scanning of silica gel plate A mixture of benzene-EtOAc-EtOH (5 : 3, 5 : 1.5) was used as the developing solvent. Recovery was 100.44%, RSD 3.0%.

Topics: Chromatography, Thin Layer; Densitometry; Drugs, Chinese Herbal; Plants, Medicinal; Rheum; Stilbenes

Topics: Anthraquinones; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Phytotherapy; Plants, Medicinal; Rheum; Senna Extract; Sennosides; Stilbenes

This paper deals with an interdisciplinary study covering historic, botanical, phytochemical, pharmacological and clinical aspects of rhubarb and related species, to lay stress on the correlation between plant phylogeny, chemical constituents and purgative activity. It was found that the official rhubarbs were exclusively restricted in the Sect. Palmata, e.g. Rheum palmatum, R. palmatum var. tanguticum, R. officinale; the following criteria may serve as their standard, viz., the presence of sennoside derivatives and rhein, the occurrence of the reduced form of rhein and aloe-emodin, the leaves with any kind of palmate incision. Comprehensive multivariate analyses showed that there is a very close relationship between the leaf incision, existence of sennosides or rhein and purgative activity.

Topics: Anthraquinones; Cathartics; Chemical Phenomena; Chemistry; Humans; Medicine, Chinese Traditional; Medicine, East Asian Traditional; Phytotherapy; Plant Extracts; Plants, Medicinal; Rheum; Stilbenes

Topics: Animals; Female; Hypolipidemic Agents; Lipids; Lipoproteins; Mice; Rabbits; Stilbenes

Topics: Acyl Coenzyme A; Acyltransferases; Carbon Radioisotopes; Plants; Stilbenes; Structure-Activity Relationship; Substrate Specificity

Topics: Anthraquinones; Glucosides; Phylogeny; Plants, Medicinal; Senna Extract; Sennosides; Species Specificity; Stilbenes

Topics: Biological Assay; Chromatography; Chromatography, Paper; Rheum; Stilbenes