cis-Aconitic Acid, a Constituent of Echinodorus grandiflorus Leaves, Inhibits Antigen-Induced Arthritis and Gout in Mice.

cis-Aconitic acid is a constituent from the leaves of Echinodorus grandiflorus, a medicinal plant traditionally used in Brazil to treat inflammatory conditions, including arthritic diseases. The present study aimed to investigate the anti-arthritic effect of cis-aconitic acid in murine models of antigen-induced arthritis and monosodium urate-induced gout. The possible underlying mechanisms of action was evaluated in THP-1 macrophages. Oral treatment with cis-aconitic acid (10, 30, and 90 mg/kg) reduced leukocyte accumulation in the joint cavity and C-X-C motif chemokine ligand 1 and IL-1ß levels in periarticular tissue. cis-Aconitic acid treatment reduced joint inflammation in tissue sections of antigen-induced arthritis mice and these effects were associated with decreased mechanical hypernociception. Administration of cis-aconitic acid (30 mg/kg p. o.) also reduced leukocyte accumulation in the joint cavity after the injection of monosodium urate crystals. cis-Aconitic acid reduced in vitro the release of TNF-α and phosphorylation of IκBα in lipopolysaccharide-stimulated THP-1 macrophages, suggesting that inhibition of nuclear factor kappa B activation was an underlying mechanism of cis-aconitic acid-induced anti-inflammatory effects. In conclusion, cis-aconitic acid has significant anti-inflammatory effects in antigen-induced arthritis and monosodium urate-induced arthritis in mice, suggesting its potential for the treatment of inflammatory diseases of the joint in humans. Additionally, our findings suggest that this compound may contribute to the anti-inflammatory effect previously reported for E. grandiflorus extracts.

Effect of the Hydroethanolic Extract from Echinodorus grandiflorus Leaves and a Fraction Enriched in Flavone-C-Glycosides on Antigen-Induced Arthritis in Mice.

The leaves of Echinodorus grandiflorus are traditionally used in Brazil to treat several inflammatory conditions, including arthritis. This study aimed to investigate the antiarthritis activity of the 70% ethanol extract of E. grandiflorus leaves and a standardized flavonoid-rich fraction in an antigen-induced arthritis model in mice. Previously immunized mice were treated per os with saline (control group), 70% ethanol extract (100-1000 mg/kg), or a flavonoid-rich fraction (0.7-7.2 mg/kg) 40 minutes before and 3 and 6 hours after the challenge with antigen into the knee joint. The administration of the 70% ethanol extract and flavonoid-rich fraction to mice significantly reduced neutrophil recruitment to the joint cavity and in periarticular tissue. The levels of chemokine (C-X-C motif) ligand 1, tumor necrosis factor-α, and interleukin-1ß quantified by the enzyme-linked immunosorbent assay (ELISA) in the periarticular tissue were also diminished in mice treated with the 70% ethanol extract and flavonoid-rich fraction, as well as mechanical hypernociception. Histological analysis confirmed that both the 70% ethanol extract and flavonoid-rich fraction suppressed joint inflammation and inhibited cartilage and bone destruction when compared to the control group. Our results demonstrate, for the first time, that E. grandiflorus has anti-inflammatory activity in an experimental arthritis model and highlights the role of flavonoids in the observed response.

In Vitro TNF-α Inhibition Elicited by Extracts from Echinodorus grandiflorus Leaves and Correlation with Their Phytochemical Composition.

This study aimed to evaluate the effect of various extracts and fractions obtained from Echinodorus grandiflorus leaves on tumor necrosis factor-α release by lipopolysaccharide-stimulated THP-1 cells, as well as to look at the association between bioactivity and phytochemical composition. To this end, a high-performance liquid chromatography with diode-array detection method was developed and validated, enabling the quantification of seven compounds in E. grandiflorus extracts and fractions. All of these samples showed antitumor necrosis factor-α activity, however, extracts prepared from 50% EtOH, water and dichloromethane, and a flavonoid-rich fraction elicited the most potent responses. trans-Aconitic acid and isoorientin were the major compounds in some preparations. Polynomial regression analysis showed the association between the contents of swertiajaponin, swertisin, trans-aconitic, and chicoric acids with the antitumor necrosis factor-α activity of the extracts and fractions. None of the compounds tested alone abolished tumor necrosis factor-α release completely, however, some extracts and fractions reached this result, suggesting a synergistic effect between the constituents. Therefore, it is clearly shown that the species E. grandiflorus has significant in vitro antitumor necrosis factor-α activity, a promising characteristic that deserves further investigations in the search for new anti-inflammatory agents from plants.

Investigação da presença de anorexígenos, benzodiazepínicos e antidepressivos em formulações fitoterápicas emagrecedoras / Investigation on the occurrence of anorexigens, benzodiazepines and antidepressants in the weight-reducer phytotherapy formulations

No Brasil, são comumente comercializadas formulações fitoterápicas emagrecedoras adicionadas de substâncias sintéticas não declaradas, o que constitui um grave problema de saúde pública. No presente trabalho, foram analisadas amostras de formulações emagrecedoras naturais com suspeita de adição de substâncias anorexígenas, ansiolíticas e/ou antidepressivas apreendidas pela Gerência de Vigilância Sanitária em Medicamentos e Congêneres/Serviço de Vigilância Sanitária de Minas Gerais (GVMC/SVSMG). Por meio de ensaios cromáticos e do teste de espuma foi constatada a ausência de pelo menos uma classe dos metabólitos secundários pesquisados (flavonoides, saponinas e quinonas) em todas as amostras analisadas. A presença de femproporex, fluoxetina e clordiazepóxido, em forma isolada ou em associação foi detectada em todas as amostras por meio de CG-EM. As amostras analisadas em sua totalidade foram discordantes dos padrões de qualidade aceitáveis, em virtude de adição não declarada de substâncias sintéticas em sua composição, além de associação de anorexígeno e ansiolítico, o que não é permitido pela legislação vigente. Comprovou-se, assim, a necessidade premente de um sistema de fiscalização mais atuante em relação a produtos irregulares comercializados, juntamente com a conscientização dos profissionais da área de saúde.

Antiedematogenic activity and phytochemical composition of preparations from Echinodorus grandiflorus leaves.

The leaves of Echinodorus grandiflorus (Alismataceae) are traditionally used in Brazil to treat inflammatory conditions. The aim of the present study was to evaluate the antidematogenic activity of crude aqueous, dichloromethane and hydroethanolic extracts from E. grandiflorus leaves using the carrageenan-induced paw edema model in mice, along with of fractions enriched in diterpenes, flavonoids and hydroxycinnamoyltartaric acids (HCTA). Significant inhibitions of paw edema were elicited by the 50% and 70% EtOH extracts (1000 mg/kg, p.o.), as well as by the fractions enriched in diterpenes (70-420 mg/kg, p.o.) and flavonoids (7.2-36 mg/kg, p.o.). Isovitexin, isoorientin, trans-aconitic and chicoric acids were identified in all extracts by HPLC analysis. Trans-aconitic acid itself exhibited significant antiedematogenic effect (270 mg/kg, p.o.). The biological activity correlated positively with the contents of flavonoids and diterpenes, but negatively with HCTA concentrations, demonstrating the participation of the two classes of compounds in the antiedematogenic activity of E. grandiflorus.