ABSTRACT
The present study investigated the antimicrobial, anti-adhesion and anti-biofilm activity of the modified synthetic molecules nitrochalcone (NC-E05) and pentyl caffeate (C5) against microorganisms which have a high incidence in hospital-acquired infections. The compounds were further tested for their preliminary systemic toxicity in vivo. NC-E05 and C5 showed antimicrobial activity, with minimum inhibitory concentrations (MICs) ranging between 15.62 and 31.25 µg ml-1. Treatment with NC-E05 and C5 at 1 × MIC and/or 10 × MIC significantly reduced mono or mixed-species biofilm formation and viability. At MIC/2, the compounds decreased microbial adhesion to HaCaT keratinocytes from 1 to 3 h (p < 0.0001). In addition, NC-E05 and C5 demonstrated low toxicity in vivo in the Galleria mellonella model at anti-biofilm concentrations. Thus, the chemical modification of these molecules proved to be effective in the proposed anti-biofilm activity, opening opportunities for the development of new antimicrobials.
Subject(s)
Anti-Infective Agents/pharmacology , Bacterial Adhesion/drug effects , Biofilms/drug effects , Caffeic Acids/pharmacology , Chalcones/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/toxicity , Anti-Infective Agents/toxicity , Antifungal Agents/pharmacology , Antifungal Agents/toxicity , Biofilms/growth & development , Caffeic Acids/toxicity , Candida albicans/drug effects , Cell Line , Cell Survival/drug effects , Chalcones/toxicity , Cross Infection/prevention & control , Humans , Keratinocytes/cytology , Keratinocytes/drug effects , Methicillin-Resistant Staphylococcus aureus/drug effects , Microbial Sensitivity Tests , Moths/drug effects , Staphylococcus aureus/drug effectsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Propolis is a bee product with numerous biological and pharmacological properties, such as immunomodulatory and anti-inflammatory activities. It has been used in folk medicine as a healthy drink and in food to improve health and prevent inflammatory diseases. However, little is known about its mechanism of action. Thus, the goal of this study was to verify the antioxidant activity and to explore the anti-inflammatory properties of propolis by addressing its intracellular mechanism of action. Caffeic acid was investigated as a possible compound responsible for propolis action. MATERIALS AND METHODS: The antioxidant properties of propolis and caffeic acid were evaluated by using the 2,2-Diphenyl-1-picrylhydrazyl free radical (DPPH) scavenging method. To analyze the anti-inflammatory activity, Raw 264.7 macrophages were treated with different concentrations of propolis or caffeic acid, and nitric oxide (NO) production, a strong pro-inflammatory mediator, was evaluated by the Griess reaction. The concentrations of propolis and caffeic acid that inhibited NO production were evaluated on intracellular signaling pathways triggered during inflammation, namely p38 mitogen-activated protein kinase (MAPK), c-jun NH2-terminal kinase (JNK1/2), the transcription nuclear factor (NF)-κB and extracellular signal-regulated kinase (ERK1/2), through Western blot using specific antibodies. A possible effect of propolis on the cytotoxicity of hepatocytes was also evaluated, since this product can be used in human diets. RESULTS: Caffeic acid showed a higher antioxidant activity than propolis extract. Propolis and caffeic acid inhibited NO production in macrophages, at concentrations without cytotoxicity. Furthermore, both propolis and caffeic acid suppressed LPS-induced signaling pathways, namely p38 MAPK, JNK1/2 and NF-κB. ERK1/2 was not affected by propolis extract and caffeic acid. In addition, propolis and caffeic acid did not induce hepatotoxicity at concentrations with strong anti-inflammatory potential. CONCLUSIONS: Propolis exerted an antioxidant and anti-inflammatory action and caffeic acid may be involved in its inhibitory effects on NO production and intracellular signaling cascades, suggesting its use as a natural source of safe anti-inflammatory drugs.
Subject(s)
Anti-Inflammatory Agents/pharmacology , Caffeic Acids/pharmacology , Free Radical Scavengers/pharmacology , Macrophages/drug effects , Mitogen-Activated Protein Kinases/antagonists & inhibitors , NF-kappa B/antagonists & inhibitors , Propolis/pharmacology , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/toxicity , Caffeic Acids/isolation & purification , Caffeic Acids/toxicity , Cell Line, Tumor , Dose-Response Relationship, Drug , Ethnopharmacology , Free Radical Scavengers/isolation & purification , Free Radical Scavengers/toxicity , Lipopolysaccharides/pharmacology , Macrophages/immunology , Mice , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/biosynthesis , Propolis/chemistry , Propolis/toxicityABSTRACT
BACKGROUND: The purpose of this investigation was to examine the effect of caffeic acid phenethyl ester (CAPE) in renal ischemia/reperfusion injury in rats anesthetized with isoflurane (iso). METHODS: We randomly assigned 26 male Wistar rats anesthetized with isoflurane, intubated and mechanically ventilated to 3 groups: G1 (controls; n = 8), G2 (CAPE; n = 10), and G3 (ethanol; n = 8). Mean arterial pressure was monitored for anesthetic control. Intraperitoneal CAPE (G2) or ethanol (G3) injections were administered 40 minutes before left renal ischemia. All animals underwent right nephrectomy and the left kidney was submitted to ischemia for 25 minutes. Serum creatinine (cr) values were determined at the beginning (M1), end (M2), and 24 hours after the experiment (M3) upon intracardiac blood samples. The left kidney was removed for histologic analysis, using a scale for tubular necrosis (0-5, injury maximum). Statistical analysis was applied to serum creatinine and histological score injury considering statistical differences to be significant when P < .05. RESULTS: The cr values in the CAPE were significantly higher at M2 (0.8 mg/mL; P = .0012) and M3 (3.7 mg/mL; P = .0014) than the control (0.5 and 0.9 mg/mL) or G3 (0.6 and 1.0 mg/mL), respectively. Histologic examination showed the CAPE group to display more pericapsular tubular necrosis (3.0 [2.0; 3.0]) than the G1 group (2.0 [1.0; 2.0]) or G3 group (1.5 [1.0; 2.0]; P < .001). The CAPE group displayed more medullary tubular necrosis (2.0 [2.0; 3.0] than G1 (2.0 [1.0; 2.0] or G3 (1.0 [0.0; 2.0]; P < .001). CONCLUSION: CAPE promoted greater functional and anatomic renal injury when rats were anesthetized with iso than control or ethanol groups, as demonstrated by histologic analysis and serum values.
Subject(s)
Anesthetics, Inhalation/toxicity , Caffeic Acids/toxicity , Isoflurane/toxicity , Kidney/blood supply , Kidney/drug effects , Phenylethyl Alcohol/analogs & derivatives , Animals , Biomarkers/blood , Creatinine/blood , Disease Models, Animal , Kidney/metabolism , Kidney/pathology , Male , Necrosis , Phenylethyl Alcohol/toxicity , Rats , Rats, Wistar , Reperfusion Injury/blood , Reperfusion Injury/chemically induced , Reperfusion Injury/etiology , Reperfusion Injury/pathology , Time FactorsABSTRACT
Phenols are a large and diverse class of compounds, many of which occur naturally in a variety of food plants; they exhibit a wide range of biological effects, including antibacterial, anti-inflammatory, antiallergic, hepatoprotective, antithrombotic, antiviral, anticarcinogenic, and vasodilatory actions. We examined the genotoxic and clastogenic potential of three phenolic compounds: caffeic, cinnamic and ferulic acids, using the comet and micronucleus assays in vitro. Drug-metabolizing rat hepatoma tissue cells (HTCs) were used. Three different concentrations (50, 500 and 1500 µM) of these phenolic acids were tested on the HTCs for 24 h. The caffeic, cinnamic and ferulic acids were not genotoxic by the comet assay (P > 0.05). However, the micronucleus test showed an increase in the frequency of micronucleated cells for the three compounds, indicating that these substances have clastogenic effects in HTC.
Subject(s)
Caffeic Acids/toxicity , Cinnamates/toxicity , Coumaric Acids/toxicity , Mutagens/toxicity , Animals , Comet Assay , In Vitro Techniques , Rats , Tumor Cells, CulturedABSTRACT
The aim of the present study was to investigate the effect of intraperitoneal administration of caffeic acid (0.5, 1, 2, 4 or 8 mg/kg) on elevated plus-maze and open field tasks in rats and its possible neuroprotection/neurotoxicity using the comet assay. Caffeic acid at 1 mg/kg increased the number of entries and the time spent in the open arms on plus-maze, suggesting an anxiolytic-like effect when used in lower doses without affecting locomotion and exploration on the open field. Furthermore, a protective effect against hydrogen peroxide-induced oxidative damage on brain tissue was observed through the treatment with caffeic acid at 1 and 8 mg/kg. However, in the highest dose, caffeic acid induced DNA damage in brain tissue.
Subject(s)
Antioxidants/toxicity , Caffeic Acids/toxicity , Exploratory Behavior/drug effects , Locomotion/drug effects , Maze Learning/drug effects , Neurotoxicity Syndromes/etiology , Animals , Brain/drug effects , Comet Assay , DNA/drug effects , DNA Damage/genetics , Dose-Response Relationship, Drug , Hydrogen Peroxide/toxicity , Injections, Intraperitoneal , Male , Neurotoxicity Syndromes/genetics , Neurotoxicity Syndromes/psychology , Oxidative Stress/drug effects , Rats , Rats, WistarABSTRACT
2',3'-Dihydroxy-4,4'-dimethoxychalcone (1) and 2',3',4-trihydroxy-4'-methoxy-chalcone, two new chalcones, were isolated from propolis from El Salvador. The compounds showed significant antibacterial and antifungal activity and moderate toxicity to Artemia salina nauplii.