RESUMO
Diabetes is part of metabolic diseases and is characterized by high blood sugar levels over a prolonged period as result of an insulin-deficient production or an inappropriate response to insulin by our cells. This chronic disease was the direct cause of 1.6 million deaths in 2016 as reported by the World Health Organization. Emodin is a natural product and active ingredient of various Chinese herbs with the chemical formula 1,3,8-trihydroxy-6-methylanthraquinone. Diacerein is another naturally occurring anthraquinone (1,8-diacetoxy-3-carboxyanthraquinone) commonly used as commercial drug to treat osteoarthritis. These two anthraquinone derivatives have been shown to exert antidiabetic activities. Emodin seems to enhance the glucose tolerance and insulin sensibility via activation of PPARγ and modulation of metabolic-related genes. Diacerein seems to decrease inflammatory cytokines and increase insulin secretion enhancing insulin sensibility and therefore improving glucose control. Other naturally occurring anthraquinone derivatives, such as catenarin (1,4,6,8-tetrahydroxy-3-methylanthraquinone), have been shown to have antidiabetic activities although few studies have been performed. The synthesis of new emodin derivatives is increasing, but these new molecules have not been tested for diabetes treatment. In the current work, available literature on anthraquinone derivatives' effects in diabetes disease is reviewed. Moreover, we discuss the chemistry, food sources, bioavailability, and toxicity of the naturally occurring anthraquinone with antidiabetic effects.
RESUMO
Nootkatone (NTK) is a sesquiterpenoid found in essential oils of many species of Citrus (Rutaceae). Considering previous reports demonstrating that NTK inhibited inflammatory signaling pathways, this study aimed to investigate the effects of this compound in mice models of acute and chronic inflammation. Murine models of paw edema induced by carrageenan, dextran, histamine, and arachidonic acid, as well as carrageenan-induced peritonitis and pleurisy, were used to evaluate the effects of NTK on acute inflammation. A murine model of granuloma induced by cotton pellets was used to access the impact of NTK treatment on chronic inflammation. In the acute inflammation models, NTK demonstrated antiedematogenic effects and inhibited leukocyte recruitment, which was associated with decreased vascular permeability, inhibition of myeloperoxidase (MPO), interleukin (IL)1-ß, and tumor necrosis factor (TNF)-α production. In silico analysis suggest that NTZ anti-inflammatory effects may also occur due to inhibition of cyclooxygenase (COX)-2 activity and antagonism of the histamine receptor type 1 (H1). These mechanisms might have contributed to the reduction of granuloma weight and protein concentration in the homogenates, observed in the chronic inflammation model. In conclusion, NTK exerted anti-inflammatory effects that are associated with inhibition of IL1-ß and TNF-α production, possibly due to inhibition of COX-2 activity and antagonism of the H1 receptor. However, further studies are required to characterize the effects of this compound on chronic inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Edema/tratamento farmacológico , Granuloma/tratamento farmacológico , Inflamação/tratamento farmacológico , Sesquiterpenos Policíclicos/farmacologia , Reação de Fase Aguda/tratamento farmacológico , Reação de Fase Aguda/metabolismo , Animais , Anti-Inflamatórios/administração & dosagem , Permeabilidade Capilar/efeitos dos fármacos , Carragenina/toxicidade , Fibra de Algodão/toxicidade , Ciclo-Oxigenase 2/química , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Edema/induzido quimicamente , Feminino , Granuloma/induzido quimicamente , Histamina/química , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Masculino , Camundongos , Simulação de Acoplamento Molecular , Peritonite/tratamento farmacológico , Peritonite/metabolismo , Peroxidase/antagonistas & inibidores , Peroxidase/metabolismo , Pleurisia/tratamento farmacológico , Pleurisia/metabolismo , Sesquiterpenos Policíclicos/administração & dosagem , Receptores Histamínicos/química , Receptores Histamínicos/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The emergence of fungal resistance to commercial drugs has been a major problem for the WHO. In this context, research with natural products is promising in the discovery of new active substances. Thus, this work evaluated the antifungal effect of a medicinal plant (i.e., Mesosphaerum suaveolens) against strains of the genus Candida, tested the combined effect with the drug fluconazole, and, finally, determined the phenolic constituents present in the species. Initially, aqueous extracts of leaves (AELMs) and aerial parts (AEAPMs) of the species were prepared. For microbiological assays, the minimum fungicidal concentration was determined by broth microdilution, and the combined effect of fluconazole extracts were verified by sub-inhibitory microdilution concentrations (CFM/8) followed by spectrophotometric readings which were used to determine the IC50. HPLC detected the presence of flavonoids and phenolic acids, detecting eight compounds present in the samples of which caffeic acid and quercetin were major components. The AELMs modulated fluconazole activity since it decreased fluconazole's IC50 from 7.8 µg/mL to an IC50 of 4.7 µg/mL (CA LM 77) and from 28.8 µg/mL to 18.26 µg/mL (CA INCQS 40006) for the C. albicans strains. The AEAPMs were able to potentiate the effect of fluconazole more effectively than the AELMs. Such an effect was significant for the 16 µg/mL concentration for CA LM 77 and 32 µg/mL for CA INCQS 40006. The AEAPMs as well as the AELMs presented clinically relevant activities for C. tropicalis strains. For the C. tropicalis LM 23 strain, the AEPMs obtained an IC50 of 25 µg/mL and the AELMs an IC50 of 359.9 µg/mL.
RESUMO
This study is a pioneer in reporting the antibacterial properties of the species Croton ceanothifolius Baill. The genus Croton belongs to the family Euphorbiaceae composed of numerous species with documented biological activities. However, the pharmacological properties of C. ceanothifolius remain poorly understood. The leaves of this plant were submitted to hydrodistillation for essential oil (CcEO) extraction and the phytochemical characterization of the oil was performed by GC/MS. The minimum inhibitory concentration of the CcEO was determined for the evaluation of antibacterial activity against multiresistant strains of Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. The antibiotic-modulating activity of the oil, in combination with antibiotics, was also evaluated. The combination of the CcEO with penicillin, norfloxacin, and gentamicin presented a synergistic effect. This effect was more significant for the association with antibiotics of the quinolone and aminoglycoside classes against Escherichia coli. The association of oil with gentamicin showed better results with regard to the Gram-positive strain. The association of the oil with norfloxacin against P. aeruginosa also showed synergism, but the association with penicillin did not change the effect of this antibiotic. Thus, it is concluded that C. ceanothifolius essential oil selectively potentiates the action of antibiotics against multiresistant strains.