RESUMO
The aim of this study was to investigate the effects of two structurally related flavonoids found in Cyclopia subternata, vicenin-2 (VCN) and scolymoside (SCL) on lipopolysaccharide (LPS)-induced liver failure in mice and to elucidate underlying mechanisms. Mice were treated intravenously with VCN or SCL at 12 h after LPS treatment. LPS significantly increased mortality, serum levels of alanine transaminase, aspartate transaminase, and inflammatory cytokines, and toll-like receptor 4 (TLR4) protein expression; these effects of LPS were inhibited by VCN or SCL. It also attenuated the LPS-induced activation of myeloid differentiation primary response gene 88 and TLR-associated activator of interferon-dependent signaling pathways of the TLR system. Our results suggest that VCN or SCL protects against LPS-induced liver damage by inhibiting the TLR-mediated inflammatory pathway, indicating its potential to treat liver diseases.
Assuntos
Apigenina/química , Glucosídeos/química , Inflamação/tratamento farmacológico , Lipopolissacarídeos/uso terapêutico , Luteolina/química , Animais , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Transdução de SinaisRESUMO
Similarity analysis of the phenolic fingerprints of a large number of aqueous extracts of Cyclopia subternata, obtained by high-performance liquid chromatography (HPLC), was evaluated as a potential tool to screen extracts for relative bioactivity. The assessment was based on the (dis)similarity of their fingerprints to that of a reference active extract of C. subternata, proven to enhance glucose uptake in vitro and in vivo. In vitro testing of extracts, selected as being most similar (n = 5; r ≥ 0.962) and most dissimilar (n = 5; r ≤ 0.688) to the reference active extract, showed that no clear pattern in terms of relative glucose uptake efficacy in C2C12 myocytes emerged, irrespective of the dose. Some of the most dissimilar extracts had higher glucose-lowering activity than the reference active extract. Principal component analysis revealed the major compounds responsible for the most variation within the chromatographic fingerprints, as mangiferin, isomangiferin, iriflophenone-3-C-ß-D-glucoside-4-O-ß-D-glucoside, iriflophenone-3-C-ß-D-glucoside, scolymoside, and phloretin-3',5'-di-C-ß-D-glucoside. Quantitative analysis of the selected extracts showed that the most dissimilar extracts contained the highest mangiferin and isomangiferin levels, whilst the most similar extracts had the highest scolymoside content. These compounds demonstrated similar glucose uptake efficacy in C2C12 myocytes. It can be concluded that (dis)similarity of chromatographic fingerprints of extracts of unknown activity to that of a proven bioactive extract does not necessarily translate to lower or higher bioactivity.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cyclopia (Planta)/química , Avaliação Pré-Clínica de Medicamentos/métodos , Glucose/metabolismo , Células Musculares/metabolismo , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Animais , Transporte Biológico/efeitos dos fármacos , Camundongos , Células Musculares/efeitos dos fármacosRESUMO
AIM AND OBJECTIVE: Recent results indicate that polyphosphate (polyP) released by human endothelial cells can function as a pro-inflammatory mediator. Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain in biological processes. This study was undertaken to investigate whether two structurally related active compounds found in C. subternata, namely vicenin-2 and scolymoside, can modulate polyP-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. METHODS: The anti-inflammatory activities of vicenin-2 and scolymoside were determined by measuring permeability, leukocytes adhesion and migration, and activation of pro-inflammatory proteins in polyP-activated HUVECs and mice. In addition, the beneficial effects of vicenin-2 and scolymoside on survival rate in polyP-injected mice were determined. RESULTS: We found that vicenin-2 and scolymoside inhibits polyP-mediated barrier disruption, the expressions of cell adhesion molecules, and leukocyte to HUVEC adhesion/migration. Interestingly, polyP-induced NF-κB activation and the productions of TNF-α and IL-6 were inhibited by vicenin-2 and scolymoside in HUVECs. These anti-inflammatory functions of vicenin-2 and scolymoside were confirmed in polyP-injected mice. CONCLUSIONS: These results suggest that vicenin-2 and scolymoside have therapeutic potential for various systemic inflammatory diseases.
Assuntos
Anti-Inflamatórios/farmacologia , Apigenina/farmacologia , Glucosídeos/farmacologia , Luteolina/farmacologia , Animais , Anti-Inflamatórios/uso terapêutico , Apigenina/uso terapêutico , Adesão Celular/efeitos dos fármacos , Moléculas de Adesão Celular/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Citocinas/metabolismo , Endotoxemia/tratamento farmacológico , Endotoxemia/metabolismo , Glucosídeos/uso terapêutico , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Leucócitos/efeitos dos fármacos , Leucócitos/fisiologia , Luteolina/uso terapêutico , Masculino , Camundongos Endogâmicos C57BL , PolifosfatosRESUMO
Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain. In this study, we investigated the antiseptic effects and underlying mechanisms of vicenin-2 and scolymoside, which are 2 active compounds from C. subternata that act against high mobility group box 1 (HMGB1)-mediated septic responses in human umbilical vein endothelial cells (HUVECs) and mice. The antiseptic activities of vicenin-2 and scolymoside were determined by measuring permeability, neutrophil adhesion and migration, and activation of proinflammatory proteins in HMGB1-activated HUVECs and mice. According to the results, vicenin-2 and scolymoside effectively inhibited lipopolysaccharide-induced release of HMGB1, and suppressed HMGB1-mediated septic responses such as hyperpermeability, the adhesion and migration of leukocytes, and the expression of cell adhesion molecules. In addition, vicenin-2 and scolymoside suppressed the production of tumor necrosis factor-α and interleukin 6, and activation of nuclear factor-κB and extracellular regulated kinases 1/2 by HMGB1. Collectively, these results indicate that vicenin-2 and scolymoside could be a potential therapeutic agents for the treatment of various severe vascular inflammatory diseases via inhibition of the HMGB1 signaling pathway.
Assuntos
Anti-Infecciosos Locais/farmacologia , Anti-Inflamatórios/farmacologia , Apigenina/farmacologia , Cyclopia (Planta) , Glucosídeos/farmacologia , Proteína HMGB1/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Luteolina/farmacologia , Sepse/tratamento farmacológico , Animais , Apigenina/isolamento & purificação , Adesão Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Técnicas de Cocultura , Cyclopia (Planta)/química , Glucosídeos/isolamento & purificação , Proteína HMGB1/antagonistas & inibidores , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Luteolina/isolamento & purificação , Masculino , Camundongos Endogâmicos C57BL , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Fitoterapia , Plantas Medicinais , Sepse/metabolismo , Sepse/microbiologia , Transdução de Sinais/efeitos dos fármacosRESUMO
Transforming growth factor ß-induced protein (TGFBIp) is an extracellular matrix protein whose expression in several cell types is greatly increased by TGF-ß. TGFBIp is released by the human umbilical vein endothelial cells (HUVECs) and functions as a mediator of experimental sepsis. Cyclopia subternata is a medicinal plant commonly used in traditional medicine to relieve pain in biological processes. In this study, we investigated the antiseptic effects and underlying mechanisms of vicenin-2 and scolymoside, two active compounds in C. subternata against TGFBIp-mediated septic responses in HUVECs and mice. The anti-inflammatory activities of vicenin-2 or scolymoside were determined by measuring permeability, human neutrophils adhesion and migration, and activation of pro-inflammatory proteins in TGFBIp-activated HUVECs and mice. According to the results, vicenin-2 or scolymoside effectively inhibited lipopolysaccharide-induced release of TGFBIp and suppressed TGFBIp-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. In addition, vicenin-2 or scolymoside suppressed the production of tumor necrosis factor-α and interleukin 6 and activation of nuclear factor-κB and extracellular regulated kinases 1/2 by TGFBIp. Vicenin-2 or scolymoside reduced cecal ligation and puncture (CLP)-induced septic mortality and pulmonary injury. Collectively, these results indicate that vicenin-2 and scolymoside could be a potential therapeutic agent for treatment of various severe vascular inflammatory diseases via inhibition of the TGFBIp signaling pathway.