Alpha-lipoic acid reduces nociception by reducing oxidative stress and neuroinflammation in a model of complex regional pain syndrome type I in mice.

Complex regional pain syndrome type I (CRPS-I) is a disabling pain condition without adequate treatment. Chronic post-ischemia pain injury (CPIP) is a model of CRPS-I that causes allodynia, spontaneous pain, inflammation, vascular injury, and oxidative stress formation. Antioxidants, such as alpha lipoic acid (ALA), have shown a therapeutic potential for CRPS-I pain control. Thus, we aim to evaluate if ALA repeated treatment modulates neuroinflammation in a model of CRPS-I in mice. We used male C57BL/6 mice to induce the CPIP model (O-ring torniquet for 2 h in the hindlimb). For the treatment with ALA or vehicle (Veh) mice were randomly separated in four groups and received 100 mg/kg orally once daily for 15 days (CPIP-ALA, CPIP-Veh, Control-ALA, and Control-Veh). We evaluated different behavioral tests including von Frey (mechanical stimulus), acetone (cold thermal stimulus), rotarod, open field, hind paw edema determination, and nest-building (spontaneous pain behavior). Also, hydrogen peroxide (H2O2) levels, NADPH oxidase and superoxide dismutase (SOD) activity in the sciatic nerve and spinal cord, and Iba1, Nrf2, and Gfap in spinal cord were evaluated at 16 days after CPIP or sham induction. Repeated ALA treatment reduced CPIP-induced mechanical and cold allodynia and restored nest-building capacity without causing locomotor or body weight alteration. ALA treatment reduced SOD and NADPH oxidase activity, and H2O2 production in the spinal cord and sciatic nerve. CPIP-induced neuroinflammation in the spinal cord was associated with astrocyte activation and elevated Nfr2, which were reduced by ALA. ALA repeated treatment prevents nociception by reducing oxidative stress and neuroinflammation in a model of CRPS-I in mice.

Analysis of nuclear maturation, DNA damage and repair gene expression of bovine oocyte and cumulus cells submitted to ionizing radiation.

Radiotherapy causes destruction of tumor cells, but also threatens the integrity and survival of surrounding normal cells. Then, woman submitted to irradiation for cancer treatment may present permanent ovary damage, resulting in impaired fertility. The objective of this study was to investigate the effects of therapeutic doses of ionizing radiation (IR), used for ovarian cancer treatment in humans, on bovine cumulus-oocyte complexes (COCs) as experimental model. Bovine ovaries were exposed to 0.9 Gy, 1.8 Gy, 3.6 Gy or 18.6 Gy IR, and then COCs were collected and used to evaluate: (a) oocyte nuclear maturation; (b) presence of phosphorylated H2A.X (γH2AX), as an indicator of DNA double-strand breaks (DSBs); and (c) expression of genes involved in DNA repair (TP53BP1, RAD52, ATM, XRCC6 and XRCC5) and apoptosis (BAX). The radiation doses tested in this study had no detrimental effects on nuclear maturation and did not increase γH2AX in the oocytes. However, IR treatment altered the mRNA abundance of RAD52 (RAD52 homolog, DNA repair protein) and BAX (BCL2-associated X protein). We conclude that although IR doses had no apparent effect on oocyte nuclear maturation and DNA damage, molecular pathways involved in DNA repair and apoptosis were affected by IR exposure in cumulus cells.

Effects of photobiomodulation on oxidative stress in rats with type 2 diabetes mellitus.

The present study aimed to evaluate photobiomodulation effects on oxidative stress in type 2 diabetes mellitus (DM2). Thirty-one male Wistar rats were used and divided into 4 groups: group 1 - animals without diabetes mellitus 2 without laser 21 J/cm2 (C-SHAM), group 2 - animals with diabetes mellitus 2 without laser 21 J/cm2 (C-DM2), group 3 - animals without diabetes mellitus 2 with laser 21 J/cm2 (L-SHAM), group 4 - animals with diabetes mellitus 2 with laser 21 J/cm2 (L-DM2). The protocol was performed 5 days/week, for 6 weeks. The animals that received photobiomodulation had one dose irradiated at two spots in the right gastrocnemius muscle. Twenty-four hours after the last intervention, the animals were euthanized. Heart, diaphragm, liver, right gastrocnemius, plasma, kidneys, weighed, and stored for further analysis. In rats with DM2, photobiomodulation promoted a decrease in thiobarbituric acid reactive substance assay (TBARS) in plasma levels. On the other hand, photobiomodulation demonstrated an increase in non-protein thiol levels (NPSH) in the heart, diaphragm and gastrocnemius. Moreover, photobiomodulation produced in the heart, diaphragm and plasma levels led to an increase in superoxide dismutase (SOD). Interestingly, photobiomodulation was able to increase superoxide dismutase in rats without DM2 in the heart, diaphragm, gastrocnemius and kidneys. These findings suggested that 6 weeks of photobiomodulation in rats with DM2 promoted beneficial adaptations in oxidative stress, with a decrease in parameters of oxidant activity and an increase in antioxidant activity.

Effect of Adding Matricaria recutita L., Cymbopogon citratus, or Mentha piperita L. Extracts to Fermented Orange Beverage: Sensory Evaluation, Physicochemical Characterization, and Prediction of Toxic Risks and Biological Activity In Silico.

Fermentation is an important tool in producing functional beverages through agro-industrial wastes, and medicinal and aromatic plants due to the specific content of bioactive molecules. Therefore, this study evaluated the contribution of Matricaria recutita (chamomile), Cymbopogon citratus (lemongrass), or Mentha piperita (peppermint) extracts to the phytochemical profile and potential biological effects of a functional fermented orange beverage in vitro and in silico. The concentrations of aromatic herbal extracts that yielded the best sensory performance for fermented beverages were selected for analyses that involved characterizing the fermented beverages. The beverages that received the extracts (2%) had the highest phenolic and flavonoid content and antioxidant potential compared to the control. Hesperidin (124-130 mg L-1), narirutin (66-70 mg L-1), chlorogenic (11-16 mg L-1), caffeic (5.3-5.5 mg L-1), and ferulic (1-1.7 mg L-1) acids were found in the different formulations. The in silico analysis suggested that the evaluated compounds do not present a toxicity risk (mutagenicity, carcinogenicity, hepatotoxicity, and ability to penetrate the blood-brain barrier). Additionally, they can contribute to the biological effects of therapeutic importance, such as antioxidant, gastroprotective, and anti-ulcerative properties, and the Mentha piperita L. extract presented the greatest potential among the evaluated herbs for use in functional fermented beverages.

Phytochemical characterisation, antioxidant capacity, and in vitro toxicity of Richardia brasiliensis gomes crude extracts.

Richardia brasiliensis is a species used in folk medicine and rich in active compounds. In this study, the extracts were submitted to UHPLC-ESI-MS/MS analysis and total polyphenols, tannins, and flavonoids assays. Besides, it was determined its antioxidant capacity, oxidative stress markers and toxicological profile. Fourteen polyphenols were found and, in the dosages, a slight change in the concentrations in each extract was observed. Regarding the antioxidant capacity, the responses were different in the methods used. There was an increase in lipid peroxidation, and NO, however total ROS remained unchanged. The cells remained more than 90% viable and the extracts did not cause damage to single strands of DNA, with the exception of the crude autumn and spring extracts at 500 µg/mL. The results found in this study suggest that extracts are potentially toxic to human leukocyte cells in high concentrations; however, more studies should be performed in different cell lines.

Caffeic acid and ferulic acid can improve toxicological damage caused by iron overload mediated by carbonic anhydrase inhibition.

The iron ion is an essential element for most forms of life, however, it can damage biological systems when found in free form. Chelation therapy is very important, but it is precarious. Caffeic and ferulic acid are antioxidant compounds with many properties described in research such as anti-inflammatory, antiobesogenic, antithrombotic, vasodilator, and anti-tumor. The aim of the study was to evaluate presenting an in silico approach on the toxicity and bioavailability of caffeic and ferulic acid, subsequently, evaluating them in an iron overload model in vivo and providing a pharmacophoric model through molecular docking. The predictive in silico test did not show relevant toxicity of the compounds, therefore, the in vivo test was performed. The rats received dextran iron and the test groups received caffeic and ferulic acid orally for six weeks. Biochemical, hematological parameters, and tissue oxidative stress marker were analyzed. The experimental model showed increased serum iron levels and changes in several serum parameters such as glucose (215.8 ± 20.3 mg/dL), ALT (512.2 ± 128.7 U/L), creatine kinase (186.8 ± 30.1 U/L), and creatine kinase isoform MB (373.3 ± 69.7 U/L). Caffeic acid and, to a lessed degree, ferullic acid, attenuated the effects of iron overload on the rat serum biochemical parameters. Docking showed a pharmacophoric model where carbonic anhydrase interacted with the test molecules and caffeic acid showed less energy expenditure in this interaction. The results illustrate a new therapeutic action of phenolic compounds on iron overload. The possible interference of carbonic anhydrase in iron metabolism needs to be elucidated.

Richardia brasiliensis Gomes: phytochemical characterization, antiproliferative capacity and in vitro and in vivo toxicity.

Richardia brasiliensis, known as poaia branca, is a medicinal species widely distributed throughout Brazil and used in folk medicine. However, studies on its toxicity are practically non-existent, and little is known about its biological activity. This study aimed to investigate its phytochemical compounds, assess its in vitro and in vivo toxicities, and determine its antiproliferative activity. UHPLC-ESI-HRFTMS performed the phytochemical characterization, and the antiproliferative activity was analyzed in different tumor cell lines. In vitro toxicity was evaluated in PBMC cells, and in vivo acute and repeated dose toxicity was evaluated according to OECD guidelines. It was identified alkaloids and terpenes as significant compounds. Regarding its antiproliferative activity, the human melanoma strain decreased its viability by about 95%. In vitro toxicity showed that the extracts maintained the viability of PBMCs; however, higher concentrations were able to increase the production of dsDNA quantity. In vivo tests showed no mortality nor signs of toxicity; the alterations found in hematological and biochemical parameters are within the standards for the species. The results indicate that R. brasiliensis has a good effect against the tumor cell line; still, more studies on its toxicity at higher concentrations are needed.

Toxicity, Anti-Inflammatory, and Antioxidant Activities of Cubiu (Solanum sessiliflorum) and Its Interaction with Magnetic Field in the Skin Wound Healing.

Cubiu, an Amazonian fruit, is widely used as food and popular treatment for pathologies that present an inflammatory pattern, such as skin wound healing. However, there is still no confirmation in the scientific literature about the safety profile, as well as the anti-inflammatory, antioxidant, and healing actions of cubiu. This study is divided into two experimental protocols using Wistar rats. Thus, the first objective (protocol 1) of this study was to evaluate the toxicity of an oral administration of cubiu extract at different doses for 28 days. The macroscopic and microscopic analyses of the liver and kidney were performed, and the following analysis was determined in plasma: glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, gamma-glutamyl transpeptidase, glucose, triglycerides, total cholesterol, urea, creatinine, and uric acid. After, we conducted the second protocol aimed to establish the potential antioxidant and anti-inflammatory capacity of cubiu and its interaction with magnetic field in skin wound healing. On days 3, 7, and 14 of treatment, skin and blood samples were collected and analyzed: the oxidative stress biomarkers (reactive substances to thiobarbituric acid, nonprotein thiols, superoxide dismutase, catalase, and glutathione S-transferase), myeloperoxidase enzymatic activity, and cytokines levels (interleukin 1, interleukin 6, interleukin 10, and tumor necrosis factor-alpha). The cubiu has shown to be safe and nontoxic. Both cubiu and magnetic field promoted decreased levels of proinflammatory and prooxidant biomarkers (interleukin 1, interleukin 6, tumor necrosis factor-alpha, and reactive substances to thiobarbituric acid), as well as increased levels of anti-inflammatory and antioxidant biomarkers (interleukin 10, nonprotein thiols, and superoxide dismutase), with greater potential when treatments are used in association. Thus, cubiu promotes antioxidant and anti-inflammatory action in skin wound healing, while also improving results of the conventional treatment for skin healing (magnetic field) when used in association.

Evaluation of the analgesic effect of ɑ-lipoic acid in treating pain disorders: A systematic review and meta-analysis of randomized controlled trials.

Neuropathic pain is the most prevalent form of chronic pain caused by a disease of the nervous system, such as diabetic polyneuropathy. ɑ-Lipoic acid (ALA) is an antioxidant that has been widely studied for the treatment of pain symptoms in diverse conditions. Therefore, this study aimed to investigate the efficacy of ALA in the treatment of different types of pain through a systematic review and meta-analysis of randomized clinical trials. The study protocol was registered in the International Prospective Registry of Systematic Reviews (CRD42021261971). A search of the databases resulted in 1154 articles, 16 of which were included in the review (9 studies with diabetic polyneuropathy and 7 studies with other painful conditions). Most of the included studies had a low risk of bias. ALA showed efficacy for the treatment of headache, carpal tunnel syndrome and burning mouth syndrome. Meta-analysis was conducted only with the studies using diabetic polyneuropathy. Compared to placebo, ALA treatment decreased the total symptom score (TSS). The subgroup meta-analysis indicated a decrease of stabbing pain, burning, paraesthesia, and numbness in ALA-treated patients compared to placebo. In addition, both routes of administration, intravenous and oral, demonstrated the efficacy to reduce TSS. Therefore, ALA should be used to treat diabetic polyneuropathy pain symptoms. However, the standardization of treatment time and the dose may advance for the approval of ALA for clinical use in diabetic polyneuroneuropathy.

Tucumã (Astrocaryum aculeatum) extract: phytochemical characterization, acute and subacute oral toxicity studies in Wistar rats.

Natural products are often used by the population to treat and/or prevent several disorders. Tucumã is an Amazonian fruit widely consumed by local population and no in vivo toxicity studies regarding its safety are available in the literature to date. Therefore, the phytochemical characterization, acute and repeated dose 28-day oral toxicities of crude extract of tucumã's pulp (CETP) in Wistar rats were evaluated. For the CETP preparation, tucumã pulp was crushed and placed into sealed amber glass jars containing absolute ethanol solution for extraction. CETP phytochemical analyses evidenced the presence of carotenoids, flavonoids, unsaturated and satured fatty acids, and triterpenes. In the acute toxicity, female rats from the test group were treated with CETP at single dose of 2000 mg/kg. For the repeated dose toxicity, CETP was administered to male and female rats at doses of 200, 400 and 600 mg/kg, for 28 days. Body weight was recorded during the experiment and blood, liver and kidney were collected for further analysis. No mortality or toxicity signs were observed during the studies. CETP was classified as safe (category 5, OECD guide), in acute toxicity. In repeated dose study was observed alterations in some biochemical parameters, as well as in oxidative damage and enzymatic activity. Histopathological findings showed renal damage in male rats at higher dose. The data obtained suggest that CETP did not induced toxicity after exposure to a single or repeated doses in female rats. However, in males may be considered safe when given repeatedly in low doses.

Randia ferox (Cham & Schltdl) DC.: phytochemical composition, in vitro cyto- and genotoxicity analyses.

Randia ferox is a Brazilian native species used in folk medicine. Scientific information regarding the toxicology and phytochemistry of this plant remains unclear. We aimed to produce a R. ferox extract, identify its chemical matrix, and evaluate its safety profile. The extract chemical composition was accessed through UHPLC-MS/MS. Mononuclear cells, erythrocytes, fibroblasts, macrophages, and kidney cells were subjected to extract concentration-response curve testing. The cellular viability, proliferation, dsDNA release, reactive oxygen species (ROS), nitric oxide (NO), hemolysis, and DNA damage were determined. Ten molecules were found in the extract matrix. Most of the tested concentrations can be considered safe. Cellular viability, proliferation, dsDNA release, and NO remained at similar levels to the control. The extract increased ROS in macrophages. None of the tested concentrations induced DNA damage or hemolysis. The data suggest R. ferox extract contains several bioactive molecules and has a safety profile in vitro.

In silico and in vivo protective effect of Morus nigra leaves on oxidative damage induced by iron overload.

Morus nigra L. is a plant popularly known as 'amoreira preta', very used in folk medicine. Iron overload (hemochromatosis) is a clinical condition that causes damage to various tissues due to oxidative stress. Therapy to control iron overload is still unsatisfactory. The protective effect on oxidative stress induced by iron overload was verified. Phytochemical characterization was evaluated by UHPLC-MS/MS. The in silico toxicity predictions of the main phytochemicals were performed via computer simulation. To induce iron overload, the animals received iron dextran (50 mg/kg/day). The test groups received doses of 500 and 1000 mg/kg of M. nigra extract for six weeks. Body weight, organosomatic index, serum iron, hepatic markers, cytokines, interfering factors in iron metabolism, enzymatic and histopathological evaluations were analyzed. Vanillic acid, caffeic acid, 6-hydroxycoumarin, p-coumaric acid, ferulic acid, rutin, quercitrin, resveratrol, apigenin and kaempferol were identified in the extract. In addition, in silico toxic predictions showed that the main compounds presented a low probability of toxic risk. The extract of M. nigra showed to control the mediators of inflammation and to reduce iron overload in several tissues. Our findings illustrate a novel therapeutic action of M. nigra leaves on hemochromatosis caused by iron overload.

Preclinical safety assessment of the crude extract from Sida rhombifolia L. aerial parts in experimental models of acute and repeated-dose 28 days toxicity in rats.

Sida rhombifolia (Malvaceae) is popularly used as a treatment for several pathological conditions; however, there is a lack of studies that identify its compounds and that evaluate comprehensively the safety of its consumption. Therefore, the aim of this study was to determinate the phytochemical constitution of the crude extract of Sida rhombifolia (CESR), and its safety in models of acute and repeated doses (28 days) toxicity. The tested dose for the model of acute toxicity was 2000 mg/kg doses for the repeated dose model were 150, 300 e 600 mg/kg. Hematological, biochemical, histopathological and oxidative markers were investigated. HPLC-DAD-MS analysis evidenced the presence of caffeic acid, coumarin, and rutin. In the acute toxicity model the only altered parameters were tissue ROS, and AST and BUN in serum. As for the repeated dose experiment both hematological and biochemical markers remained within the values of reference for the species. Obtained results demonstrate that the CESR did not present significant toxic effects when administrated orally to male and female rats in acute and repeated doses.

Hydroalcoholic extract of leaf of Arachis hypogaea L. (Fabaceae) did not induce toxic effects in the repeated-dose toxicity study in rats.

Arachis hypogaea L. (peanut) leaf is traditionally used for the treatment of insomnia in Asia. However, studies describing the safety and toxicity profile for this plant preparation are limited. Thus, the goal of this study was to investigate the toxicity of peanut leaf hydroalcoholic extract (PLHE) repeated treatment. The extract was administered orally (100, 300 or 1000 mg/kg) in male and female Wistar rats for 28 days (OECD guideline 407). PLHE treatment did not cause mortality or weight variation in the animals. Also, there was no alteration on locomotor activity (open field test), motor coordination (rotarod test), or anxiety behaviour (elevated plus-maze test). Male rats had a reduction in relative liver weight (100 mg/kg) and an increase in total kidney weight (1000 mg/kg), but there was no change in biochemical and haematological parameters after PLHE treatment. Free extracellular double-stranded DNA (dsDNA) levels was also evaluated, but PLHE treatment did not increase this parameter in rat organs. Also, the dose of 1000 mg/kg of PLHE significantly increased the total thiols in the liver of females compared with the control animals. Thus, PLHE did not induce toxicity after repeated exposure for 28 days in rats.

Casearia decandra leaves present anti-inflammatory efficacy in a skin inflammation model in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Casearia decandra (guaçatonga) is popularly used as an anti-inflammatory. We investigated the antioxidant and anti-inflammatory effect of C.decandra leaves (CdE) ethanolic extract and of the rutin standard (present in the CdE). MATERIALS AND METHODS: Male adult Swiss mice were used (25-30 g; 5-6 animals by a group). CdE phytochemical analysis was performed by HPLC method. The antioxidant potential of CdE and rutin was assessed by different methods. Topical anti-inflammatory effect of CdE (0.001-1mg/ear) and rutin (0.003-0.03mg/ear) was evaluated by ear edema formation and inflammatory cells infiltration (MPO activity and histology) on a skin inflammation model induced by topical application of croton oil (1mg/ear). RESULTS: Rutin (27.81 ± 1.11 mg/g) was identified in CdE by HPLC analysis. The required amounts of CdE, rutin and ascorbic acid to reduce the initial concentration of radical DPPH by 50% (IC50) were 7.77 (6.31-9.57) µg/mL, 3.62 (3.26-4.01) µg/mL and 3.74 (3.37-4.14) µg/mL with a radical DPPH reduction of 91 ± 1.2%, 91 ± 0.5%, and 96 ± 0.44% (at 30 µg/mL), respectively. Moreover, CdE and rutin presented H2O2 scavenging activity with H2O2 levels reduction of 41 ± 7% and 46 ± 6%, respectively and SOD-like activity of 60 ± 4% and 51 ± 14%, respectively. On the other hand, just rutin presented nitric oxide scavenging activity of 54 ± 6%. CdE and rutin topically applied inhibited the ear edema with a maximum inhibition of 70 ± 5% (1 mg/ear) and 78 ± 10% (0.03 mg/ear), respectively. Treatments reduced the MPO activity (42 ± 4% to CdE; 1mg/ear and 30 ± 8% to rutin; 0.03 mg/ear). Histologically, the topical treatments also reduced the dermis thickness and the inflammatory cells infiltration. CONCLUSION: We demonstrated the antioxidant and anti-inflammatory effect of C.decandra leaves and rutin. Its antioxidant potential may contribute to inflammatory process attenuation, supporting the C.decandra leaves used as a promising alternative in the therapy of the inflammatory diseases.

Superoxide-hydrogen peroxide imbalance differentially modulates the keratinocytes cell line (HaCaT) oxidative metabolism via Keap1-Nrf2 redox signaling pathway.

The purpose of this study was to investigate the effect of a superoxide-hydrogen peroxide (S-HP) imbalance of the superoxide dismutase manganese dependent (SOD2) gene, generated by paraquat and porphyrin exposure, on the keratinocytes cell line (HaCaT) oxidative metabolism. Paraquat acts increasing superoxide (O2·-) levels, while porphyrin increases hydrogen peroxide (H2O2) levels, acting as VV-SOD2-like and AA-SOD2-like molecules, respectively. First of all, HaCAT cells were treated with different concentrations of paraquat and porphyrin (1; 10; 30, and 70 µM) to determine the concentration of both that causes imbalance. After defining the concentration of paraquat and porphyrin (70 µM), a time curve was performed (1, 3, 6, and 24 h) to evaluate ROS production levels. Other oxidative parameters, such as nitric oxide (NO), lipoperoxidation (TBARS) and protein carbonyl, were evaluated after 24 h of incubation, as well as genotoxic analyses, apoptosis detection, and gene expression. Our findings revealed that paraquat exposure decreased cell viability, increasing lipoperoxidation, DNA damage, and apoptosis. On the other hand, porphyrin treatment increased cell viability and proliferation, ROS and NO production, triggering protein and DNA damage. In addition, porphyrin up-regulated Keap1 and Nrf2 gene expression, while paraquat decreased Nrf2 gene expression. In this sense, we suggested that the superoxide-hydrogen peroxide imbalance differentially modulates oxidative stress on keratinocytes cell line via Keap1-Nrf2 gene expression pathway.

Peanut leaf extract has antioxidant and anti-inflammatory activity but no acute toxic effects.

Arachis hypogaea L. (peanut) leaves have been popularly used for the treatment of insomnia and inflammation, but no toxicological study has been performed for this plant preparation. This study aimed to examine the phytochemical composition of peanut leaf hydroalcoholic extract (PLHE) and describe its potential toxic effects and antioxidant and anti-inflammatory properties. The qualitative chemical analysis of PLHE by UHPLC-ESI-HRMS allowed the identification of eight metabolites types (totaling 29 compounds). The 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay revealed that PLHE had strong antioxidant effects; it also exhibited nitric oxide (NO)-scavenging capacity. Human peripheral blood mononuclear cells (PBMCs) exposed to PLHE showed no reduced cell viability or increased free double-stranded DNA, NO, or reactive species production. PLHE reversed the cytotoxicity, pro-inflammatory (release of interleukin-1ß), and pro-oxidant effects of H2O2 on human PBMCs. Acute PLHE toxicity analysis was performed in vivo using the Organization for Economic Co-operation and Development (OECD) 423 guidelines. PLHE single injection (2000 mg/kg, intragastric) did not cause mortality or morbidity or induce changes in hematological or biochemical parameters after 14 days of administration. Thus, PLHE could be a source of bioactive compounds and possesses antioxidant and anti-inflammatory properties without elicitin cytotoxicity or genotoxicity in human PBMCs or acute toxicity in rats.

Antidiabetic effects of Olea europaea L. leaves in diabetic rats induced by high-fat diet and low-dose streptozotocin.

ETHNOPHARMACOLOGICAL RELEVANCE: Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia, insulin resistance, and dyslipidemia. It has broad occurrence worldwide, affecting millions of people, and can cause serious complications. The olive (Olea europaea L.) has important pharmacological functions, including anti-inflammatory, antioxidant, and hypoglycemic activities. Olive leaves are used in traditional medicine for diabetes and hypertension. AIM OF THE STUDY: To evaluate the effect of the ethanolic extract of olive leaves (EEOL) on the metabolism of rats with diabetes induced by a high-fat diet and low dose of streptozotocin (STZ). MATERIALS AND METHODS: Male Wistar rats were either given normal feed or a high-fat diet (70% standard laboratory feed, 15% sucrose, 10% lard and 5% yolk powder) for four weeks, followed by administration of STZ (35 mg/kg, via ip). Animals with fasting glucose levels above 200 mg/dL were considered diabetic. Animals were divided into 5 groups, which received ethanol (10 mL/kg), metformin (250 mg/kg), or EEOL at doses of 200 and 400 mg/kg during 10 weeks by oral gavage. Blood samples were used to measure hematological and biochemical parameters, and kidneys were removed for posterior analysis. Body weight was recorded weekly. RESULTS: A significant decrease in body weight was observed among diabetic animals treated with ethanol and EEOL compared to the control group. Moreover, animals treated with EEOL showed an improvement in glucose levels and in levels of inflammatory and metabolic markers when compared to diabetic animals. CONCLUSIONS: The results indicate a potential anti-diabetic activity of olive leaves, however more studies are needed to validate clinical effects.

Acute toxicity and antimicrobial activity of leaf tincture Baccharis trimera (Less).

BACKGROUND: The present study aimed to evaluate the possible acute oral toxicity of Baccharistrimera leaf dye as well as its antimicrobial activity. METHOD: Organization for Economic co-operation and development (OECD) 423 was used to assess acute oral toxicity and as per protocol a dose of 2000 mg/kg of tincture was administered to Wistar rats, male and female, and observed for 14 days. Biochemical and hematological analyzes were performed with sample collected of rat. The dye was evaluated for antimicrobial activity by agar diffusion and microdilution methods, which allow to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) and antibiofilm potential. RESULTS: The results showed that there was no loss of animals and no significant changes in hematological and biochemical parameters after oral administration of 2000 mg/kg of tincture and was considered safe by the OECD, classified as category 5. The dyeing also showed an important antimicrobial activity against gram positive and gram negative bacteria also significantly decreased the microbial biofilm. CONCLUSION: The tincture of B.trimera leaf when given orally once can be considered safe and has a relevant antimicrobial potential that should be elucidated in subsequent research.

In vitro antimicrobial and antimycobacterial activity and HPLC-DAD screening of phenolics from Chenopodium ambrosioides L

Abstract The main objective of this study was to demonstrate the antimicrobial potential of the crude extract and fractions of Chenopodium ambrosioides L., popularly known as Santa-Maria herb, against microorganisms of clinical interest by the microdilution technique, and also to show the chromatographic profile of the phenolic compounds in the species. The Phytochemical screening revealed the presence of cardiotonic, anthraquinone, alkaloids, tannins and flavonoids. The analysis by HPLC-DAD revealed the presence of rutin in the crude extract (12.5 ± 0.20 mg/g), ethyl acetate (16.5 ± 0.37 mg/g) and n-butanol (8.85 ± 0.11 mg/g), whereas quercetin and chrysin were quantified in chloroform fraction (1.95 ± 0.04 and 1.04 ± 0.01 mg/g), respectively. The most promising results were obtained with the ethyl acetate fraction, which inhibited a greater number of microorganisms and presented the lowest values of MIC against Staphylococcus aureus and Enterococcus faecalis (MIC = 0.42 mg/mL), Pseudomonas aeruginosa (MIC = 34.37 mg/mL), Paenibacillus apiarus (MIC = 4.29 mg/mL) and Paenibacillus thiaminolyticus (MIC = 4.29 mg/mL). Considering mycobacterial inhibition, the best results were obtained by chloroform fraction against M. tuberculosis, M. smegmatis, and M. avium (MIC ranging from 156.25 to 625 µg/mL). This study proves, in part, that the popular use of C. ambrosioides L. can be an effective and sustainable alternative for the prevention and treatment of diseases caused by various infectious agents.