RESUMO
A new rare-earth polyborate, trisodium europium octaborate, Na3EuB8O15, was prepared using the high-temperature molten-salt method and structurally determined by single-crystal X-ray diffraction analysis. It crystallizes in the triclinic space group P-1 and contains a one-dimensional [B8O15]∞ tube structure that is constructed from BO3 and BO4 polyhedra. The Eu3+ and Na+ cations reside in this structure to ensure cohesion and neutrality. The excitation spectra, emission spectra, decay time and Commission Internationale de l'Éclairage (CIE) chromaticity index of Na3EuB8O15 were studied. Under near-UV light excitation (393â nm), the polyborate shows an intense red emission, which mainly originates from the highest intensities of the 5D0â7F1 and 5D0â7F2 transitions.
RESUMO
Ginsenoside Rh2 is one of the most important ginsenosides in ginseng with anti-inflammatory and antitumor effects. However, the extremely poor oral bioavailability induced by its low water solubility greatly limits the potency of Rh2 in vivo. In the previous study, we sulfated 20(S)-ginsenoside Rh2 with chlorosulfonic acid and pyridine method, and got one novel derivative, Rh2-B1, with higher water solubility and greater immunologic enhancement than Rh2. However, the anti-inflammatory effect of Rh2-B1 remains unclear. We therefore investigated the effects of Rh2-B1 on lipopolysaccharide (LPS)-induced proinflammatory mediators in RAW 264.7 macrophages. We found that Rh2-B1 dramatically inhibited LPS-induced overproduction of nitric oxide, prostaglandin E2, tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6. Consistently, the protein and mRNA expression levels of inducible nitric oxide synthase and cyclooxygenase-2 were remarkably decreased by Rh2-B1. In addition, Rh2-B1 significantly suppressed the phosphorylations of p38, c-Jun N-terminal kinase, and extracellular signal receptor-activated kinase 1/2 induced by LPS. Rh2-B1 was further shown to inhibit NF-κB p65 translocation into the nucleus by suppressing IκBα degradation. In conclusion, we demonstrate that Rh2-B1 inhibits the release of LPS-induced pro-inflammatory mediators through blocking mitogen-activated protein kinases and NF-κB signaling pathways, suggesting that sulfated ginsenosides could be potential agents for anti-inflammatory therapies.
Assuntos
Ginsenosídeos/química , Ginsenosídeos/farmacologia , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Sulfatos/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Linhagem Celular , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Macrófagos/citologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Ginsenoside Rh2 is one of the most important ginsenosides in ginseng with antitumor, antidiabetic, antiallergic, and anti-inflammatory effects. However, the extremely poor oral bioavailability induced by its low water solubility greatly limits the potency of Rh2 in clinical use. Therefore, in this study we sulfated 20(S)-ginsenoside Rh2 with chlorosulfonic acid and pyridine method, and got two new sulfated derivatives, Rh2-B1 and Rh2-B2, with higher water solubility. Their chemical structures were characterized by spectroscopic methods (IR, MS and NMR). Additionally, Rh2-B1 and Rh2-B2 had the greater anti-inflammatory effects than Rh2 through inhibiting inflammatory cytokines and mediators in LPS-induced mouse RAW264.7 macrophages cells. These results suggested that the sulfated modification of Rh2 improved its water solubility and the sulfated derivatives could be more potential candidates for developing as anti-inflammatory agents.
Assuntos
Citocinas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Lipopolissacarídeos/toxicidade , Macrófagos/efeitos dos fármacos , Animais , Linhagem Celular , Citocinas/genética , Macrófagos/metabolismo , CamundongosRESUMO
In the previous study, we found that sulfated derivative B2 of ginsenoside Rh2 (Rh2-B2) has greater anti-inflammatory effects than 20(S)-ginsenoside Rh2. However, the anti-inflammatory mechanism of Rh2-B2 remains unclear. We therefore assessed the effects of Rh2-B2 on inflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. We found that Rh2-B2 (1-5 mg/L) significantly inhibited tumor necrosis factor alpha, interleukin (IL)-6, IL-1ß, and increased IL-10 production from protein and mRNA levels. Furthermore, Rh2-B2 significantly inhibited the phosphorylation of p38 and c-Jun N-terminal kinase as well as decreased p65 nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) translocation into the nucleus by nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha degradation. The present results indicate that Rh2-B2 inhibits the production of inflammatory cytokines induced by LPS through blocking mitogen-activated protein kinases and NF-κB signaling pathways.
