Antioxidant activity and mechanisms of action of natural compounds isolated from lichens: a systematic review.

Chronic diseases such as cancer, diabetes, neurodegenerative and cardiovascular diseases are characterized by an enhanced state of oxidative stress, which may result from the overproduction of reactive species and/or a decrease in antioxidant defenses. The search for new chemical entities with antioxidant profile is still thus an emerging field on ongoing interest. Due to the lack of reviews concerning the antioxidant activity of lichen-derived natural compounds, we performed a review of the antioxidant potential and mechanisms of action of natural compounds isolated from lichens. The search terms "lichens", "antioxidants" and "antioxidant response elements" were used to retrieve articles in LILACS, PubMed and Web of Science published until February 2014. From a total of 319 articles surveyed, 32 met the established inclusion and exclusion criteria. It was observed that the most common isolated compound studied was usnic acid, cited in 14 out of the 32 articles. The most often described antioxidant assays for the study of in vitro antioxidant activity were mainly DPPH, LPO and SOD. The most suggested mechanisms of action were scavenging of reactive species, enzymatic activation and inhibition of iNOS. Thus, compounds isolated from lichens are possible candidates for the management of oxidative stress, and may be useful in the treatment of chronic diseases.

Submillisecond optical reporting of membrane potential in situ using a neuronal tracer dye.

A major goal in neuroscience is the development of optical reporters of membrane potential that are easy to use, have limited phototoxicity, and achieve the speed and sensitivity necessary for detection of individual action potentials in single neurons. Here we present a novel, two-component optical approach that attains these goals. By combining DiO, a fluorescent neuronal tracer dye, with dipicrylamine (DPA), a molecule whose membrane partitioning is voltage-sensitive, optical signals related to changes in membrane potential based on FRET (Förster resonance energy transfer) are reported. Using DiO/DPA in HEK-293 cells with diffraction-limited laser spot illumination, depolarization-induced fluorescence changes of 56% per 100 mV (tau approximately 0.1 ms) were obtained, while in neuronal cultures and brain slices, action potentials (APs) generated a Delta F/F per 100 mV of >25%. The high sensitivity provided by DiO/DPA enabled the detection of subthreshold activity and high-frequency APs in single trials from somatic, axonal, or dendritic membrane compartments. Recognizing that DPA can depress excitability, we assayed the amplitude and duration of single APs, burst properties, and spontaneous firing in neurons of primary cultures and brain slices and found that they are undetectably altered by up to 2 microm DPA and only slightly perturbed by 5 microm DPA. These findings substantiate a simple, noninvasive method that relies on a neuronal tracer dye for monitoring electrical signal flow, and offers unique flexibility for the study of signaling within intact neuronal circuits.

Specific immunosuppression by immunotoxins containing daunomycin.

Daunomycin, when conjugated with a targeting antigen by an acid-sensitive spacer, remains inactive at the intravascular pH of 7 but becomes active after cleavage within the acidic lysosomal environment of the target cell. This observation made it possible to construct cytocidal compounds that caused antigen-specific suppression of murine lymphocyte function. When daunomycin was coupled to the hapten conjugate of ovalbumin by an acid-sensitive cis-aconityl group, it caused hapten-specific impairment of immunocompetence in murine B lymphocytes in vitro and in vivo. Furthermore, the response by T lymphocytes to concanavalin A in vitro was selectively eliminated by a conjugate between daunomycin plus the acid-sensitive spacer and a monoclonal antibody specific for T cells.

Two-dimensional immune profiles improve antigen microarray-based characterization of humoral immunity.

Antigen arrays are becoming widely used tools for the characterization of the complexity of humoral immune responses. Current antibody profiling techniques provide modest and indirect information about the effector functions of the antibodies that bind to particular antigens. Here we introduce an antigen array-based approach for obtaining immune profiles reflecting antibody functionality. This technology relies on the parallel measurement of antibody binding and complement activation by features of the array. By comparing sera from animals immunized against the same antigen under different conditions, we show that identifying the position of an antigen in a 2-D space, derived from antibody binding and complement deposition, permits distinction between immune profiles characterized by diverse antibody isotype distributions. Additionally, the technology provides a biologically interpretable graphical representation of the relationship between antigen and host. Our data suggest that 2-D immune profiling could enrich the data obtained from proteomic scale serum profiling studies.

Suppression of regucalcin mRNA expression in the hearts of rats administered with free radical compound: the administration-induced death is accelerated in regucalcin transgenic rats.

The expression of regucalcin, a regulatory protein in the intracellular signaling system, in the hearts of rats was investigated. Regucalcin expression was examined using reverse transcription-polymerase chain reaction and Western blot analysis. Regucalcin mRNA and its protein levels in the hearts of male and female rats were significantly decreased with increasing age (50 weeks old) as compared with that of 5-week-old rats. The effect of 1,1-diphenyl-2-picryl-hydrazyl (DPPH), a compound that produces free radical, on regucalcin mRNA expression in the hearts of female rats (5 weeks old) was examined. Heart regucalcin mRNA levels were significantly decreased at 60 or 180 min after a single intraperitoneal administration of DPPH (0.5 mg /100 g body weight), suggesting that free radical stress has a suppressive effect on the gene expression. Normal (wild) female rats died at approximately 300 min after a single intraperitoneal administration of DPPH (0.5 mg/100 g), while regucalcin transgenic (TG) female rats died at approximately 150 min after the administration. Heart regucalcin protein in DPPH-administered rats was greater in regucalcin TG rats than in normal (wild) rats. This study demonstrates that the death of regucalcin TG rats is accelerated after the administration of free radical compound, indicating that overexpression of regucalcin does not have effects as the suppressor for free radical stress and the scavenger for free radical in rats.

Comparative toxicity study of 2,4,6-trinitrophenol (picric acid) in newborn and young rats.

The toxicity of oral 2,4,6-trinitrophenol (TNP) was determined in newborn rats, and compared with that in young rats. In newborn rats, males and females were given TNP at 0, 16.3, 81.4 or 407 mg/kg per day on postnatal days (PND) 4-17 for the dose-finding study, and at 0, 4.1, 16.3 or 65.1 mg/kg per day on PND 4-21 for the main study. Deaths, lower body weight (BW) and behavioral changes were found at 81.4 and 407 mg/kg per day in the dose-finding study, and lower BW was observed in males at 65.1 mg/kg per day during the dosing period of the main study. In young rats, 5-week-old males and females were given TNP at 0, 20, 100 or 500 mg/kg per day for 14 days as the dose-finding study and at 0, 4, 20 or 100 mg/kg per day for 28 days as the main study. Deaths were observed at 500 mg/kg per day in the dose-finding study. Deaths or changes in BW were not found at 100 mg/kg per day or less. At 100 mg/kg per day, hemolytic anemia and testicular toxicity were found. In conclusion, toxicity profiles induced by TNP were markedly different between newborn and young rats.

Dietary antioxidant supplements: benefits of their combined use.

Several dietary supplements claim medicinal benefits due to their composition in hydrophilic and lipophilic molecules, natural extracts or synthetic compounds with antioxidant properties. In the present work, the antioxidant activity of selected supplements taken in pills, capsules or infusions were studied either individually or combined. Linear discriminant analysis (LDA) was used to categorize the condensed formulations (pills and capsules), infusion bags and combined samples according with their antioxidant activity measured by radical scavenging activity, reducing power and lipid peroxidation inhibition using brain homogenates as models. AAF proved to have the highest antioxidant activity in all the assayed methods, either singly taken or included in mixtures. Furthermore, the mixtures containing this supplement revealed synergistic effects in 92% of the cases. The intake of antioxidant mixtures might provide some additional benefits.