RESUMO
Celiac disease (CD) is an autoimmune condition that occurs in genetically predisposed people where the ingestion of gluten produces damage in the small intestine. The treatment accepted until now is a strict gluten free diet. This implies the need for novel or adjuvant treatments, in addition to the standard of care. The present study aimed to assess the effect of gold nanoparticles phytosynthesized with Cornus mas extract (AuCM) compared to Cornus mas extract (CM) and luteolin (LT) on Caco-2 cells, exposed or not to gliadin. Ultraviolet-visible spectroscopy and transmission electron microscopy were used for the characterization of AuCM. Measured cellular outcomes included oxidative stress markers (malondialdehyde level, catalase and superoxide dismutase activities), inflammatory response and cellular signaling and transcription factors involved in apoptosis (NFκB, pNFκB, NOS2, TNF-α, TRAIL, Bax, Bcl-2, p53). The internalization of gold nanoparticles in cells was evidenced by transmission electron microscopy (TEM). The gliadin administration induced oxidative stress, improved the activity of antioxidants enzymes, increased NOS2 and NFκB expressions and reduced pNFκB/NFκB ratio. In addition, gliadin enhanced TRAIL and Bcl-2 levels and reduced p53 expression in Caco-2 cells. The pretreatment with AuCM, CM extract and LT diminished oxidative stress and reduced NOS2 activity. AuCM and CM treatment amplified the expression of p53 and pNFκB/NFκB ratio and diminished Bcl-2, NFκB and pNFκB, especially AuCM. The results obtained confirmed that AuCM mitigate some of gliadin effects on Caco-2 cells through modulation of oxidative stress and inflammation.
Assuntos
Neoplasias do Colo/tratamento farmacológico , Cornus/química , Gliadina/toxicidade , Ouro/química , Nanopartículas Metálicas/administração & dosagem , Extratos Vegetais/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Células CACO-2 , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/patologia , Humanos , Inflamação/tratamento farmacológico , Nanopartículas Metálicas/química , Estresse Oxidativo/efeitos dos fármacosRESUMO
Tropaeolum majus L. (T. majus) or nasturtium is a medicinal plant widespread in the areas with temperate climate, commonly used in culinary and in traditional medicine due to therapeutic properties. In the last few years, various effects of the flowers and leaves of this plant have been studied, but their benefits are not fully known. The aim of the study was to identify the phenolic compounds from T. majus edible flowers in relation with its antioxidant capacity and the antimicrobial activity against different bacteria and Candida albicans. In addition, the impact of natural extract on oxidative stress, inflammation and apoptosis was analysed on human umbilical vein endothelial cells (HUVECs) exposed to normotonic and hypertonic conditions. The major phenolic acids, identified by HPLC-RP with UV detection, were gallic acid, caffeic acid and p-coumaric and predominant flavonoids were quercetin, epicatechin and luteolin. The both fractions of T. majus were rich sources of polyphenols with marked antioxidant activity, evidenced by TEAC or DPPH methods. The extract exhibited a week antibacterial effect on some strains of streptococcus, without antifungal or antibacterial effect on gram negative bacteria. T. majus extract increased the p53 and Bcl-2 expressions and diminished the DNA lesions indicating the protective and antiapoptotic effects in vitro, on endothelial cells exposed to hyperosmotic stress. These experimental findings suggest that T. majus can exert some protection against bacterial infections and reduce apoptosis and DNA lesions in hypertonic conditions.
Assuntos
Antibacterianos/farmacologia , Antioxidantes/farmacologia , Extratos Vegetais/farmacologia , Tropaeolum , Apoptose/efeitos dos fármacos , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Candida albicans/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Dano ao DNA , Flores , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Interleucina-6/metabolismo , Malondialdeído/metabolismo , Pressão Osmótica , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
Anxiety disorders can associate with oxidative stress and immune system alterations. Our study aimed to chemically analyze Hypericum maculatum (HM) and Hypericum perforatum (HP) dry extracts and to evaluate their effects along with quercetin (Q), on brain oxidative stress biomarkers: malondialdehyde (MDA), catalase (CAT) and superoxide dismutase (SOD), inflammatory cytokines: interleukin-1α, (IL-1α), IL-1ß, regulated on activation normal T cell expressed and secreted (RANTES), interferon (IFN), monocyte chemoattractant protein-1 (MCP1), macrophage inflammatory protein (MIP) and serum corticosterone levels. Nuclear transcription factor κB (NFκB) signaling pathway in the hippocampus and frontal lobe in rats with N-methyl-9H-pyrido[5,4-b]indole-3-carboxamide (FG-7142) experimental-induced anxiety were also investigated. The chemical analyses of total hypericins were performed by spectrophotometric analysis and hypericin, hyperforin and polyphenols derivatives were quantified by chromatographic methods. The animals were divided in 6 groups: carboxymethylcellulose 2% (CMC); CMC + FG; alprazolam (APZ) + FG; Q + FG; HM + FG; HP + FG. APZ (0.08 mg/kg b.w.), Q (30 mg/kg b.w.), HM and HP (350 mg/kg b.w.) were orally administered for 21 days. FG (7.5 mg/kg b.w.) was intraperitoneally (i.p.) injected in a single dose. Q and hypericum extracts (HpE) exerted anti-inflammatory (decreased IL-1α, IL-1ß, MCP1, IFN and MIP mainly in hippocampus) and antioxidant effects (decreased MDA levels, increased CAT and SOD activity), enhanced NFκB and pNFκB expressions in the brain and reduced serum corticosterone levels. Our findings suggest that HpE may improve anxiety-like behavior, offer brain protection by modulation of oxidative stress and inflammation, and can contribute to overall biological activity of natural compounds-rich diet.
Assuntos
Ansiolíticos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Ansiedade/tratamento farmacológico , Hypericum , Extratos Vegetais/uso terapêutico , Animais , Ansiedade/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Corticosterona/sangue , Citocinas/metabolismo , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos WistarRESUMO
Photochemoprevention with natural products represents a new concept in the attempt to reduce the occurrence of skin cancer. However, the molecular mechanisms caused by ultraviolet light exposure remain still unclear. The aim of the study was to assess the mechanisms involved in the action of a Calluna vulgaris (Cv) extract, administered in single or multiple doses (10 consecutive days), on UVB-induced skin damage in SKH-1 hairless mice. The extract was topically applied 30 min before each UVB exposure in two doses (2.5 and 4 mg total polyphenolic content/40 µl/cm(2)). At 24 hours after the last treatment, total mitogen-activated protein kinase (p44/42MAPkinase, ERK 1/2), nuclear factor-κB (phospho-NF-κB p65), matrix metalloproteinases (MMP-2, MMP-9) and metalloproteinase inhibitor 1 (TIMP-1) levels were measured in skin using enzyme-linked immunosorbent assay (ELISA). MMP-2 and -9 activities were additionally evaluated by zymography. One topical application of Cv extract reduced the secretion (p<0.004) and inhibited MMP-9 activity UVB-mediated (54% inhibition) via inhibition of NF-κB activation (68% inhibition). In multiple UVB exposures, both doses of Cv extract induced the increase of ERK 1/2 level in correlation with activation of NF-κB and reduced the secretion (p<0.04) and activation of MMP-9 (62% inhibition). Pretreatment with Cv diminished the MMP-2 protein secretion only in one dose UVB-irradiated group (p<0.0001) and decreased TIMP-1 level (p<0.001). These results demonstrated the dual behavior of Cv extract in skin protection against single versus multiple doses of UVB irradiation.