Infusion from Miconia albicans (Melastomataceae) leaves exhibits anti-inflammatory and anti-hyperalgesic activities without toxicity.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Miconia albicans have been extensively used as a traditional medicine to treat inflammation, infection, arthritis, joint pain, and analgesia, which can be purchased easily. Nevertheless, the scientific evidence of chemical profile identification and toxicity investigation is meager. AIM OF THE STUDY: This study aimed to determine the chemical profile of Miconia albicans aqueous extract (MAAE), to investigate its anti-inflammatory and hyperalgesic effects, and toxicity (acute and repeated-dose oral) in vivo studies. MATERIALS AND METHODS: MAAE was obtained by infusion method and its chemical constituents were analyzed and annotated by LC-DAD-MS. The in vivo tests were performed with male and female Swiss mice. Toxicity studies were examined by acute (2000 mg/kg) and repeated-dose oral assays (51.2; 256; 1280 mg/kg); anti-inflammatory evaluation was performed by paw edema and leukocyte migration, and anti-hyperalgesic properties were analyzed by abdominal writhing induced by acetic acid and formalin. The animals were treated by oral means with 51.2, 256, and 1280 mg/kg of MAAE. RESULTS: Twenty-four compounds were annotated from MAAE by LC-DAD-MS, such as ellagitannins, ellagic acid derivatives, flavan-3-ol, and O-glycosylated compounds, including flavonols, triterpenes, and megastigmanes. MAAE induced no significant toxicological effects in the acute and repeated-dose oral assays at lower doses and no histological changes were observed. Hematological and biochemical showed no significant alterations. The oral administration of MAAE 256 mg/kg inhibited the edematogenic effect and reduced the leukocyte migration. In addition, MAAE decreased the abdominal writhings induced by acetic acid and the paw-licking time by formalin assay. CONCLUSION: MAAE showed a significant reduction in inflammatory levels and leukocyte migration, revealing anti-hyperalgesic properties. Additionally, MAAE revealed no acute and repeated-doses toxicities.

Neuroprotective Effects of Acrocomia aculeata Pulp Oil Microcapsules on Rats Subjected to Chronic Stress.

Acrocomia aculeata fruits are rich in monounsaturated fatty acid, ß-carotene, tocopherol, and other antioxidant compounds. The aim of our study was to investigate and compare the protective effects of A. aculeata pulp oil and microencapsulated pulp oil on brain oxidative damage induced by chronic restraint stress (CRS) in rats (cortex, hippocampus, and striatum). Thirty-six Wistar rats were divided into six treatment groups: C, P, and M groups received 1 µL/g of body weight of distilled water, pulp oil, and pulp oil microcapsules by daily gavage, respectively. The SC, SP, and SM groups received 1 µL/g of body weight of distilled water, pulp oil, and pulp oil microcapsules by daily gavage, respectively, and were then subjected to uninterrupted 6 h of CRS. After 21 days of testing, the rats were euthanized and the brain tissue of the groups was removed for evaluation for oxidative damage markers and antioxidant enzymes. Endpoints of oxidative stress (OS) markers (lipid peroxidation, protein carbonylation, and reduced glutathione [GSH]) and antioxidant enzymes (superoxide dismutase and catalase) were evaluated. By imposing chronic stress on rats, pulp oil and microcapsules of pulp oil induced positive antioxidant responses, mainly by increasing the GSH content, increasing the ability of neural tissues to deal with inherent OS, thus protecting against neurodegenerative diseases. The administration of A. aculeata pulp oil and microencapsulated pulp oil made the reversal of the oxidant parameters, which may protect the brain tissue of rats altered by CRS. The Clinical Trial Registration number: n° 1.008/2018 CEUA/UFMS.

Buriti pulp oil did not improve high-fat diet-induced metabolic disorders in c57bl/6 mice.

Metabolic syndrome (MetS) and obesity are growing in many parts of the world, becoming public health problems. It is proposed that foods with functional properties can assist in the treatment of these diseases. Crude buriti pulp oil (BPO) is a food traditionally consumed by residents in the Pantanal, Cerrado and Brazilian Amazon. It is rich in oleic acid, tocopherols and carotenoids, emerging as a potential functional food. Thus, this study aimed to evaluate the effect of the supplementation of BPO on metabolic disorders caused by a high-fat diet. Four groups of C57BL6 mice were used, a lean group with AIN-93M diet and control oil supplementation, an obese group with a high-fat diet and control oil supplementation, and two obese groups with a high-fat diet and BPO supplementation in the amounts of 50 and 100 mg/kg. BPO worsened the metabolic state caused by the high-fat diet, worsening risk factors associated with MetS, as the abdominal circumference and retroperitoneal fat, serum levels of total cholesterol, uric acid, alanine transaminase, glucose and triglycerides, and renal fat, in addition to changes in glycaemic control and oxidative stress markers. C57BL/6 mice fed with a high-fat diet and supplemented with BPO presented a worsening in metabolic risk factors associated with MetS.

Phenolic Compounds Isolated from Calea uniflora Less. Promote Anti-Inflammatory and Antioxidant Effects in Mice Neutrophils (Ex Vivo) and in Mice Pleurisy Model (In Vivo).

The literature shows that phenolic compounds possess important antioxidant and anti-inflammatory activities; however, the mechanism underlying these effects is not elucidated yet. The genus Calea is used in folk medicine to treat rheumatism, respiratory diseases, and digestive problems. In this context, some phenolic compounds were isolated with high purity from Calea uniflora Less. and identified as noreugenin (NRG) and α-hydroxy-butein (AH-BU). The aim of this study was to analyze the effect of these compounds on cell viability, the activity of myeloperoxidase (MPO), and apoptosis of mouse neutrophils using ex vivo tests. Furthermore, the effect of these compounds on the cytokines, interleukin 1 beta (IL-1ß), interleukin 17A (IL-17A), and interleukin 10 (IL-10), and oxidative stress was investigated by analyzing lipid peroxidation (the concentration of thiobarbituric acid reactive substances (TBARS)) and activities of antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), and glutathione S-transferase (GST), using a murine model of neutrophilic inflammation. The NRG and AH-BU reduce MPO activity and increase neutrophil apoptosis (p < 0.05). These compounds reduced the generation of oxygen reactive species and IL-1ß and IL-17A levels but increased IL-10 levels (p < 0.05). This study demonstrated that NRG and AH-BU show a significant anti-inflammatory effect by inhibiting the MPO activity and increasing neutrophil apoptosis in primary cultures of mouse neutrophils. These effects were at least partially associated with blocking reactive species generation, inhibiting IL-1ß and IL-17A, and increasing IL-10 levels.

N-acetylcysteine and alpha-lipoic acid improve antioxidant defenses and decrease oxidative stress, inflammation and serum lipid levels in ovariectomized rats via estrogen-independent mechanisms.

Sexual hormone deficiency has been associated with metabolic changes, oxidative stress and subclinical inflammation in postmenopausal women. Hormone replacement therapies are effective in many instances, even though some patients either do not respond or are not eligible. The aim of this study was to evaluate the impact of short- (15 days) versus long-term (60 days) sexual hormone depletion and whether antioxidant supplementation with N-acetylcysteine (NAC) and alpha-lipoic acid (LA) improves oxidative stress, metabolic, and inflammatory parameters in ovariectomized (OVX) rats. Short-term OVX rapidly depleted circulating estrogen, causing uterine atrophy and body weight gain without affecting oxidative damage, inflammatory and lipid metabolism markers. In contrast, long-term OVX augmented oxidative damage in serum and peripheral tissues as well as increased serum total cholesterol, TNF-α and IL6 levels. Triglycerides, glucose and HDL cholesterol were not altered. Long-term OVX-induced oxidative stress was associated with depletion of GSH and total non-enzymatic antioxidants as well as decreased activity of Glutathione Peroxidase (GPx) and Glutathione Reductase (GR), but not Superoxide Dismutase (SOD) and Catalase (CAT). NAC and LA supplementation prevented GSH and total non-enzymatic antioxidants depletion as well as restored GPx and GR activities, TNF-α, IL6 and cholesterol in OVX rats. NAC and LA effects appear to be independent on NRF2 activation and estrogen-like activity, since NAC/LA did not promote NRF2 activation and were not able to emulate estrogen effects in OVX rats and estrogen-receptor-positive cells. The herein presented data suggest that NAC and LA may improve some deleterious effects of sexual hormone depletion via estrogen-independent mechanisms.

Persistence of the benefit of an antioxidant therapy in children and teenagers with Down syndrome.

This study examined the effect of an antioxidant intervention in biomarkers of inflammation and oxidative stress (OS) in the blood of Down syndrome (DS) children and teenagers during four different stages. A control group was composed by healthy children (n=18), assessed once, and a Down group composed by DS patients (n=21) assessed at the basal period (t0), as well as after 6 months of antioxidant supplementation (t1), after 12 months (after interruption of the antioxidant intervention for 6 months) (t2), and again after further 6 months of antioxidant supplementation (t3). Biomarkers of inflammation (myeloperoxidase activity - MPO and levels of IL-1ß and TNF-α) and OS (thiobarbituric acid reactive substances - TBARS, protein carbonyls - PC), reduced glutathione (GSH), uric acid (UA) and vitamin E levels, as well as antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST) and gamma-glutamyltransferase (GGT) activities, were measured after each period. After the antioxidant supplementation, the activities of SOD, CAT, GPx, GR, GGT and MPO were downregulated, while TBARS contents were strongly decreased, the contents of GSH and vitamin E were significantly increased, and no changes in G6PD and GST activity as well as in UA and PC levels were detected. After the interruption of the antioxidant therapy for 6 months, DS patients showed elevated GPx and GGT activities and also elevated UA and TBARS levels. No changes in SOD, CAT, GR, GST, G6PD and MPO activities as well as in GSH, vitamin E, PC, TNF-α and IL-1ß levels were detected. The results showed that the antioxidant intervention persistently attenuated the systemic oxidative damage in DS patients even after a relatively long period of cessation of the antioxidant intervention.

Antioxidant intervention attenuates oxidative stress in children and teenagers with Down syndrome.

We previously demonstrated that systemic oxidative stress is present in Down syndrome (DS) patients. In the present study we investigated the antioxidant status in the peripheral blood of DS children and teenagers comparing such status before and after an antioxidant supplementation. Oxidative stress biomarkers were evaluated in the blood of DS patients (n=21) before and after a daily antioxidant intervention (vitamin E 400mg, C 500 mg) during 6 months. Healthy children (n=18) without DS were recruited as control group. The activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione S-transferase (GST), gamma-glutamyltransferase (GGT), glucose-6-phosphate dehydrogenase (G6PD) and myeloperoxidase (MPO), as well as the contents of reduced glutathione (GSH), uric acid, vitamin E, thiobarbituric acid reactive substances (TBARS), and protein carbonyls (PC) were measured. Before the antioxidant therapy, DS patients presented decreased GST activity and GSH depletion; elevated SOD, CAT, GR, GGT and MPO activities; increased uric acid levels; while GPx and G6PD activities as well as vitamin E and TBARS levels were unaltered. After the antioxidant supplementation, SOD, CAT, GPx, GR, GGT and MPO activities were downregulated, while TBARS contents were strongly decreased in DS. Also, the antioxidant therapy did not change G6PD and GST activities as well as uric acid and PC levels, while it significantly increased GSH and vitamin E levels in DS patients. Our results clearly demonstrate that the antioxidant intervention with vitamins E and C attenuated the systemic oxidative damage present in DS patients.

Anticancer activity of flavonol and flavan-3-ol rich extracts from Croton celtidifolius latex.

CONTEXT: Croton celtidifolius Baill (Euphorbiaceae) is a tree found in the Atlantic Forest in Southern Brazil, where it is commonly known as "Sangue-de-Dragão". Its red latex is used traditionally for treating ulcers, diabetes and cancer. OBJECTIVE: To evaluate antitumor activities of Croton celtififolius latex in vitro and in vivo. MATERIAL AND METHODS: Phytochemical analyses were conducted using HPLC-DAD-MS. Cytotoxic, nuclease and pro-apoptotic properties were determined using the tetrazolium salt assay (MTT), plasmid DNA damage assay and ethidium bromide (EB)/acridine orange methods, respectively, and antitumor activity was determined in the Ehrlich ascites carcinoma (EAC) mouse model. RESULTS: Phytochemical studies indicated a high phenol content of flavonols (45.67 ± 0.24 and 18.01 ± 0.23 mg/mL of myricetin and quercetin, respectively) and flavan-3-ols (114.12 ± 1.84 and 1527.41 ± 16.42 mg/L of epicatechin and epigallocatechin, respectively) in latex. These compounds reduced MCF-7 and EAC cell viability in the MTT assay (IC50 = 169.0 ± 1.8 and 187.0 ± 2.2 µg/mL, respectively). Latex compounds caused significant DNA fragmentation and increased the number of apoptotic cells (negative control (NC), 12%; latex, 41%) as indicated by differential staining in the EB/acridine orange assay. The in vivo latex treatment at 3.12 mg/kg/day reduced the body weight by 7.57 ± 2.04 g and increased median survival time to 17.5 days when compared to the NC group (13.0 days). In addition, the highest latex concentration inhibited tumor growth by 56%. DISCUSSION AND CONCLUSION: These results agree with ethno-pharmacological reports showing cytotoxicity and antitumor activity of C. celtidifolius latex. The mechanism of antitumor action may be related to direct DNA fragmentation that reduces survival and induces apoptosis.

Antioxidant intervention compensates oxidative stress in blood of subjects exposed to emissions from a coal electric-power plant in South Brazil.

In the process of energy generation, particulate matter (PM) emissions derived from coal combustion expose humans to serious occupational diseases, which are associated with overgeneration of reactive oxygen species (ROS). The purpose of the present study is to better understand the relations between PM exposure derived from a coal electric-power plant and the oxidative damage in subjects (n=20 each group) directly (working at the burning area) or indirectly (working at the office or living in the vicinity of the electric-power plant=group of residents) exposed to airborne contamination, before and after daily supplementation with vitamins C (500mg) and E (800mg) during six months, which were compared to non-exposed subjects (control group). Several biomarkers of oxidative stress were examined such as levels of thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), protein thiols (PT) and vitamin E in plasma, levels of reduced glutathione (GSH) in whole blood, and of activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) in red cells. Before supplementation, TBARS and PC levels were significantly increased, levels of GSH and vitamin E were decreased, while the activities of SOD and CAT were increased in workers groups and GST were increased in all groups in compared to controls. After the antioxidant supplementation essentially all these biomarkers were normalized to control levels. The antioxidant intervention was able to confer a protective effect of vitamins C and E against the oxidative insult associated with airborne contamination derived from coal burning of an electric-power plant.

Antioxidant therapy attenuates oxidative insult caused by benzonidazole in chronic Chagas' heart disease.

Chronic chagasic cardiac patients are exposed to oxidative stress that apparently contributes to disease progression. Benznidazole (BZN) is the main drug used for the treatment of chagasic patients and its action involves the generation of reactive species. 41 patients with Chagas' heart disease were selected and biomarkers of oxidative stress were measured before and after 2 months of BZN treatment (5 mg/kg/day) and the subsequent antioxidant supplementation with vitamin E (800 UI/day) and C (500 mg/day) during 6 months. Patients were classified according to the modified Los Andes clinical hemodynamic classification in groups IA, IB, II and III, and the activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glutathione reductase (GR), as well as the contents of reduced glutathione (GSH), thiobarbituric acid reactive species (TBARS), protein carbonyl (PC), vitamin E and C and nitric oxide (NO), myeloperoxidase (MPO) and adenosine deaminase (ADA) activities were measured in their blood. Excepting in group III, after BZN treatment SOD, CAT, GPx and GST activities as well as PC levels were enhanced while vitamin E levels were decreased in these groups. After antioxidant supplementation the activities of SOD, GPx and GR were decreased whereas PC, TBARS, NO, and GSH levels were decreased. In conclusion, BZN treatment promoted an oxidative insult in such patients while the antioxidant supplementation was able to attenuate this effect by increasing vitamin E levels, decreasing PC and TBARS levels, inhibiting SOD, GPx and GR activities as well as inflammatory markers, mainly in stages with less cardiac involvement.