Propolis from stingless bees Tetragonisca fiebrigi found in Brazil is used in folk medicine by their nutritional and therapeutic properties. However, there are no scientific records evidencing such properties. The present study was designed to investigate the chemical composition and the biological properties of propolis from T. fiebrigi. For this, the chemical composition of the ethanol extract of propolis (EEP) was determined by GC-MS and presented phenolic compounds, alcohol, and terpenes as its major class compounds. The antimicrobial activity was accessed in gram-positive and gram-negative bacteria and in fungi, isolated from different biological fluids and reference strains. The EEP was active against all microorganisms and showed antioxidant activity by scavenging free radicals, inhibiting hemolysis and lipid peroxidation in human erythrocytes incubated with an oxidizing agent. The anti-inflammatory potential of the EEP was confirmed by inhibition of the hyaluronidase enzyme. The cytotoxic activity was concentration-dependent against K562 cells, with a predominance of death by necrosis. Taken together, these results show that propolis from T. fiebrigi has important therapeutic activities, which suggest its potential application in the pharmaceutical industry, as well as in health foods, beverages, and nutritional supplements.

Background/Aims: Recent evidence shows a critical role of the CD4+ T cell with the Th1/Th2 paradigm as a possible effector mechanism in ischemia and reperfusion injury. We hypothesize that a polarized Th1 activation response may negatively influence the renal IRI through its relationship with chemokine production (MCP-1) and with a protective tissue response (HO-1). Methods: We subjected mice to renal ischemia for 45 min using IL-4 and IL-12 knockout C57BL/6. We then measured serum urea levels, performed histomorphometric analysis for tubular necrosis and regeneration, and evaluated the mRNA expression of HO-1, t-bet, Gata-3 and MCP-1 by real-time PCR at 24, 48 and 120 h after surgery. Results/Conclusions: The IL-4 knockout mice had a statistically significant rise in serum urea levels post IRI compared with control animals. The IL-12-deficient mice were not affected. The IL-4-deficient mice had a statistically significant increase in tubular injury and impairment in cell regeneration. The IRI in IL-4-deficient mice was accompanied by higher levels of HO-1, t-bet and later up-regulation of MCP-1. These findings suggest that the deleterious effects of the Th1 cell involve increased production of chemokines such as MCP-1.

Ischemia and reperfusion injury (IRI) is the main etiology of acute renal failure in native and transplanted kidneys. In the transplantation field, immunosuppressive drugs may play an additional role in acute graft dysfunction. Rapamycin may impair renal regeneration post IRI. Heme oxygenase 1 (HO-1) is a protective gene with anti-inflammatory and anti-apoptotic actions. We investigated whether HO-1 played a role in rapamycin-induced renal dysfunction in an established model of IRI. Rapamycin (3 mg/kg) was administered to mice before being subjected to 45 min of ischemia. Animals subjected to IRI presented with impaired renal function that peaked at 24 h (2.05+/-0.23 mg/dl), decreasing thereafter. Treatment with rapamycin caused even more renal dysfunctions (2.30+/-0.33 mg/dl), sustained up to 120 h after reperfusion (1.54+/-0.4 mg/dl), when compared to the control (0.63+/-0.09 mg/dl, P<0.05). Rapamycin delayed tubular regeneration that was normally higher in the control group at day 5 (68.53+/-2.30 vs 43.63+/-3.11%, P<0.05). HO-1 was markedly upregulated after IRI and its expression was even enhanced by rapamycin (1.32-fold). However, prior induction of HO-1 by cobalt protoporphyrin improved the renal dysfunction imposed by rapamycin, mostly at later time points. These results demonstrated that rapamycin used in ischemic-injured organs could also negatively affect post-transplantation recovery. Modulation of HO-1 expression may represent a feasible approach to limit rapamycin acute toxicity.

Acute liver damage caused by acetaminophen overdose is a significant clinical problem and could benefit from new therapeutic strategies. Objective. This study investigated the hepatoprotective effect of Thymus vulgaris essential oil (TEO), which is used popularly for various beneficial effects, such as its antiseptic, carminative, and antimicrobial effects. The hepatoprotective activity of TEO was determined by assessing serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) in mice. Their livers were then used to determine myeloperoxidase (MPO) enzyme activity and subjected to histological analysis. In vitro antioxidant activity was evaluated by assessing the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH•)-scavenging effects of TEO and TEO-induced lipid peroxidation. TEO reduced the levels of the serum marker enzymes AST, ALT, and ALP and MPO activity. The histopathological analysis indicated that TEO prevented acetaminophen-induced necrosis. The essential oil also exhibited antioxidant activity, reflected by its DPPH radical-scavenging effects and in the lipid peroxidation assay. These results suggest that TEO has hepatoprotective effects on acetaminophen-induced hepatic damage in mice.

Ischemia reperfusion injury (IRI) is a potential contributor for the development of chronic allograft nephropathy. T cells are important mediators of injury, even in the absence of alloantigens. We performed a depletion of TCD4(+)CTLA4(+)Foxp3(+) cells with anti-CD25(PC61), a treatment with anti-GITR (DTA-1) and rat-IgG, followed by 45 min of ischemia and 24/72 h of reperfusion, and then analyzed blood urea, kidney histopathology and gene expression in kidneys by QReal Time PCR. After 24 h of reperfusion, depletion of TCD4(+)CTLA4(+)Foxp3(+) cells reached 30.3%(spleen) and 67.8%(lymph nodes). 72 h after reperfusion depletion reached 43.1%(spleen) and 90.22%(lymph nodes) and depleted animals presented with significantly poorer renal function, while DTA-1(anti-GITR)-treated ones showed a significant protection, all compared to serum urea from control group (IgG: 150.10+/-50.04; PC61: 187.23+/-31.38; DTA-1: 64.53+/-25.65, mg/dL, p<0.05). These data were corroborated by histopathology. We observed an increase of HO-1 expression in animals treated with DTA-1 at 72 h of reperfusion with significant differences. Thus, our results suggest that PC61(anti-CD25) mAb treatment is deleterious, while DTA-1(anti-GITR) mAb treatment presents a protective role in the renal IRI, indicating that some regulatory populations of T cells might have a role in IRI.

Summary Ischemic‐reperfusion injury (IRI) triggers an inflammatory response involving neutrophils/macrophages, lymphocytes and endothelial cells. Galectin‐3 is a multi‐functional lectin with a broad range of action such as promotion of neutrophil adhesion, induction of oxidative stress, mastocyte migration and degranulation, and production of pro‐inflammatory cytokines. The aim of this study was evaluate the role of galectin‐3 in the inflammation triggered by IRI. Galectin‐3 knockout (KO) and wild type (wt) mice were subjected to 45 min of renal pedicle occlusion. Blood and kidney samples were collected at 6, 24, 48 and 120 h. Blood urea was analyzed enzymatically, while MCP‐1, IL‐6 and IL‐1β were studied by real‐time PCR. Reactive oxygen species (ROS) was investigated by flow cytometry. Morphometric analyses were performed at 6, 24, 48 and 120 h after reperfusion. Urea peaked at 24 h, being significantly lower in knockout animals (wt = 264.4 ± 85.21 mg/dl vs. gal‐3 KO = 123.74 ± 29.64 mg/dl, P = 0.001). Galectin‐3 knockout animals presented less acute tubular necrosis and a more prominent tubular regeneration when compared with controls concurrently with lower expression of MCP‐1, IL‐6, IL‐1β, less macrophage infiltration and lower ROS production at early time points. Galectin‐3 seems to play a role in renal IRI involving the secretion of macrophage‐related chemokine, pro‐inflammatory cytokines and ROS production.

Natural products can be a source of biomolecules with antioxidant activity which are able to prevent oxidative stress-induced diseases and show antitumor activity, making them important sources of new anticancer drug prototypes. In this context, this study aimed to analyze the chemical composition of an ethanol extract of Senna velutina leaves and to assess its antioxidant and cytotoxic activities in leukemic cells. The antioxidant properties were evaluated using a DPPH free radical scavenging assay and by examining the extract's inhibition of AAPH-induced lipid peroxidation in human erythrocytes. Its cytotoxicity and possible mechanisms of action were assessed in Jurkat and K562 leukemic cell lines. The ethanol extract contained flavonoids, such as epigallocatechin, epicatechin, kaempferol heteroside, rutin, and dimeric and trimeric proanthocyanidin derivatives. The extract exhibited antioxidant activity by scavenging free radicals and antihemolytic action, and it decreased malondialdehyde content in human erythrocytes. Furthermore, the extract also induced leukemic cell death by activating intracellular calcium and caspase-3, decreasing mitochondrial membrane potential, and arresting the cell cycle in S and G2 phases. Hence, S. velutina leaf extract contains antioxidant and antileukemic biomolecules with potential applications in diseases associated with oxidative stress and in the inhibition of tumor cell proliferation.

Essential oils are potential sources of novel components for medicinal use. The present study was performed to investigate the composition and anti-inflammatory activity of Ocimum americanum L. essential oil (OEO) and its components in an experimental model of zymosan-induced arthritis and paw edema. The essential oil was obtained by hydro-distillation and analyzed by gas chromatography-mass spectrometry. Twenty-six components, representing 98.9% of the total oil, were characterized, with linalool (19.63%) and 1,8-cineole (17.27%) as the main components. The OEO and its two constituents inhibited leukocyte influx into the synovial space and reduced paw edema induced by zymosan. The OEO also inhibited interferon-γ levels but did not reduce transforming growth factor-β levels. Additionally, the OEO protected against leukocyte influx into the synovial membrane and cartilage destruction in knee joints in arthritic mice. These findings indicate that the essential oil of Ocimum americanum L. exerted significant anti-inflammatory effects, likely related to its main compounds.