rhapontin and rhapontigenin

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

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

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

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

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

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

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

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