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Evidence suggests that prenatal maternal immunological stress is associated with an increased risk of neurological and psychiatric disorders in the developing offspring. Protecting the embryo during this critical period of neurodevelopment, when the brain is especially vulnerable, is therefore crucial. Polyphenols, with their antioxidant and anti-inflammatory properties, offer promising therapeutic approaches. This study demonstrated a series of behavioral changes induced by maternal immune activation (MIA) triggered by an antigenic solution derived from the H1N1 virus. These changes include significant differences in anxiety and risk assessment behaviors, increased immobility in the forced swim test, impairments in memory and object recognition, and social deficits resembling autism. The phenolic compound resveratrol (RSV) was evaluated for its in vitro antioxidant capacity and characterized using infrared spectroscopy. Administering RSV from embryonic day 14 (E14) to embrionyc day 19 (E19) during MIA effectively reduced its harmful effects on the offspring. This was evidenced by a significant restoration of social behaviors, memory, and recognition, as well as anxiolytic and antidepressant effects in the adult offspring. These findings contribute to new therapeutic strategies for preventing psychiatric disorders associated with neurodevelopmental stressors., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) has been applied to determine salivary biomarkers with high sensitivity and cost-effectiveness. Our study aimed to test the hypothesis that the spectral profile of saliva demonstrates distinct vibrational modes corresponding to different exercise protocols, thereby facilitating exercise monitoring. Saliva samples were collected from trained male subjects at three intervals: pre-exercise, post-exercise, and 3 h post-exercise. The protocols included acute sessions of continuous exercise (CE), high-intensity interval exercise (HIIE), and resistance exercise (RE). ATR-FTIR analysis revealed that salivary biochemical components changed uniquely with each exercise protocol. Specific spectral vibrational modes were identified as potential biomarkers for each exercise type. Notably, the salivary spectrum pattern of CE closely resembled that of HIIE, whereas RE showed minor alterations. Furthermore, we attempted to apply an algorithm capable of distinguishing the spectral range that differentiates the exercise modalities. This pioneering study is the first to compare changes in saliva spectra following different exercise protocols and to suggest spectrum peaks of vibrational modes as markers for specific types of exercises. We emphasize that the spectral wavenumbers identified by FTIR could serve as practical markers in distinguishing between different exercise modalities, with sensitivity, specificity, and accuracy correlating with the metabolic changes induced by exercise. Therefore, this study contributes a panel of ATR-FTIR spectral wavenumbers that can be referenced as a spectral signature capable of distinguishing between resistance and endurance exercises., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Chronic unpredictable mild stress (CUMS) is a widely accepted method for inducing depressive-like states in animal models. We decided to explore the effects of CUMS on the CantonS lineage of Drosophila melanogaster, which differs from the OregonR lineage in various ways. Additionally, we wanted to investigate the potential benefits of kefir in treating these chronically stressed flies, as previous research has shown promising results in using kefir components for depression treatment. To begin, we exposed male CantonS flies to a 10-day CUMS protocol and compared them to non-stressed flies. Within the stressed group, we had two subgroups: one treated with kefir (CUMS + Kefir group) and the other treated with sertraline (positive control). We then analysed various factors including serotonin levels, brain structure, markers of oxidative damage in lipids and proteins, and behavioural manifestations such as sociability, locomotor function, and anhedonic-like behaviour. Our results showed that flies exposed to CUMS experienced a decrease in serotonin levels without any signs of degeneration. They also exhibited reduced sociability, increased motor agitation, and decreased sucrose consumption, which are all indicative of stress-induced depressive-like behaviour. However, treatment with sertraline partially reversed these effects. Interestingly, treatment with kefir not only restored serotonin levels but also improved sociability and anhedonic-like behaviours. Additionally, flies in the CUMS + Kefir group had a longer lifespan compared to their untreated counterparts. These findings suggest that kefir has multiple advantageous effects on flies subjected to the 10-day CUMS protocol. In conclusion, our study demonstrates that the CantonS lineage of D. melanogaster displays depressive-like manifestations after exposure to CUMS. Furthermore, kefir emerges as a powerful nutritional tool capable of reversing these effects and promoting beneficial outcomes in chronically stressed flies.

Type 2 diabetes mellitus is a global health problem, placing patients at a higher risk of developing cardiovascular diseases and cancer. This study investigates the antidiabetic potential of Cassia bakeriana bark extracts and fractions. We evaluate their ability to inhibit α-amylase and α-glucosidase enzymes and advanced glycation end-products (AGEs). The antioxidant potential was also examined. Extracts were prepared through maceration with hexane (HE) and ethanol (EE), and the fractions were obtained via liquid-liquid extraction from EE. Anti-enzymatic, anti-glycation, antioxidant, and cytotoxic assays were conducted in 96-well plates using different concentrations of samples to determine the half-maximal inhibitory concentration (IC 50 ). Active samples were further analyzed using HPLC-(-)-ESI-MS/MS. The ethyl acetate fraction (EAF) demonstrated a high percentage of α-amylase inhibition (94.0%) with a promising IC 50 value of 1.05 μg mL -1 . Additionally, EAF displayed 61.5% inhibition of α-glucosidase, with an IC 50 value of 537 μg mL -1 . The EE, EAF, and n-butanol fraction (BF) exhibited strong anti-glycation capacities. Furthermore, the EE, EAF, BF, and dichloromethane fractions showed promising antioxidant activity using the DPPH and ORAC methodologies. Cytotoxic activity was also evaluated with Vero cells, revealing no adverse effects on cell viability (CC 50  > 512.0 μg mL -1 ). Active samples predominantly comprised proanthocyanidins, flavonoids, and anthraquinone, representing the main constituents of C. bakeriana bark. This study provides the first assessment of the antidiabetic potential of C. bakeriana bark and a comprehensive analysis of the chemical composition of its active extracts and fractions, offering hope for future treatments., (© 2024 John Wiley & Sons Ltd.)

Doxorubicin (DOX) is a potent chemotherapeutic agent used to treat multiple types of cancer, but its clinical application is limited by cardiotoxicity, mainly due to oxidative stress. Curcumin (CUR) is a natural polyphenolic compound with strong antioxidant properties, but its potential protective effects against DOX-induced cardiotoxicity need further investigation. This study aimed to evaluate CUR's efficacy in mitigating DOX-induced oxidative stress in the hearts of BALB/c mice. Mice received a DOX dose of 9 mg/kg or 16 mg/kg; half of the mice received daily doses of 100 mg/kg CUR for 15 days. Survival analysis, histopathological examination, and oxidative stress markers were assessed to determine the cardioprotective effects of CUR. Results showed that CUR significantly reduced oxidative damage and improved survival rates, particularly at the lower DOX dose (9 mg/kg). Mice treated with DOX-9 mg/kg plus CUR showed improved health conditions and reduced levels of reactive oxygen species (ROS), lipid peroxidation, sulfhydryl production, and protein carbonylation. Histopathological analysis confirmed reduced cardiac tissue damage. In conclusion, CUR combined with a lower dose of DOX effectively reduces oxidative stress and cardiac injury, enhancing survival in BALB/c mice. These findings suggest that CUR is a promising adjunct therapy to mitigate DOX-induced cardiotoxicity, potentially improving the DOX therapeutic index in cancer treatment.

The Pfaffia glomerata, a plant popularly called Brazilian ginseng, is widely used in Brazil for the treatment of various pathologies, including those associated with the Central Nervous System. 20-hydroxyecdysone (20E), a phytosteroid present in this plant, can promote adaptogenic effects in the organism, providing greater body resistance to stressors. This study aimed to evaluate the phytochemical composition and the anticholinesterase, antioxidant, and antiglycation effects of extracts and fractions of aerial parts and roots of P. glomerata, also analyzing their possible cytotoxic effects. The fractions were obtained by partitioning methanol extracts from the aerial part and roots of P. glomerata with hexane, dichloromethane, ethyl acetate, n-butanol, and water. The samples were initially tested in anticholinesterase, antioxidant, and antiglycation assays, and the most promising samples were submitted for cytotoxicity and chromatographic analyses. Mass spectrometry and chromatography methods revealed that 20E was the main compound in the dichloromethane fractions, there being 35% more 20E in the aerial part (APD) than in the roots (RD). Added to the higher concentration of 20E, the APD fraction also presented more promising results than the RD fraction in anticholinesterase and antioxidant analyses, indicating that their effects may be related to the concentration of 20E. These same fractions showed no hemolytic effects but were cytotoxic in high concentrations. These new findings contribute to scientific information about P. glomerata and open more perspectives for the understanding of its therapeutic properties, allowing the association of biological activity with the presence of 20E., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

The study aimed to assess the chemical composition of Miconia ibaguensis leaves extracts and fractions obtained from the ethanolic extract (EE), along with evaluating their antifungal, antibacterial, antidiabetic, and antioxidant activities. The ethyl acetate fraction (EAF) exhibited potent antifungal activity against Candida spp (1.95-3.90 μg mL -1 ) and potent antioxidant activity in the DPPH (1.74±0.07 μg mL -1 ), FRAP (654.01±42.09 μmol E Trolox /g sample ), and ORAC (3698.88±37.28 μmol E Trolox /g sample ) methods. The EE displayed inhibition against the α-amylase enzyme (8.42±0.05 μg mL -1 ). Flavonoids, hydrolysable tannins, triterpenoids, and phenolic acids, identified in the EE and fractions via (-)-HPLC-ESI-MS/MS analysis, were found to contribute to the species' biological activity potentially. These findings suggest promising avenues for further research and potential applications in pharmacology and natural products, offering new possibilities in the fight against global health issues., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

This study explores the green synthesis of silver nanoparticles (AgNPs) using a methanolic extract of fermented pollen from Tetragonisca angustula, a species of stingless bees. The AgNPs exhibit spherical morphology, low charge values, and suspension stability, with their unique composition attributed to elements from the pollen extract. Antioxidant assays show comparable activity between the pollen extract and AgNPs, emphasizing the retention of antioxidant effects. The synthesized AgNPs demonstrate antimicrobial activity against multidrug-resistant bacteria, highlighting their potential in combating bacterial resistance. The AgNPs exhibit no toxic effects on Drosophila melanogaster and even enhance the hatching rate of eggs. The study underscores the innovative use of stingless bee pollen extract in green synthesis, offering insights into the varied applications of AgNPs in biomedicine., (© 2024. The Author(s).)

Embryonic development is exceptionally susceptible to pathogenic, chemistry and mechanical stressors as they can disrupt homeostasis, causing damage and impacted viability. Oxidative stress has the capacity to induce alterations and reshape the environment. However, the specific impacts of these oxidative stress-induced damages in the gastrointestinal tract of Drosophila melanogaster larvae have been minimally explored. This study used 2,2-azobis (2-amidinopropane) dihydrochloride (AAPH), a free radical generator, to investigate oxidative stress effects on Drosophila embryo development. The results showed that exposing Drosophila eggs to 30 mM AAPH during 1st instar larva, 2nd instar larva and 3rd instar larva stages significantly reduced hatching rates and pupal generation. It increased the activity of antioxidant enzymes and increased oxidative damage to proteins and MDA content, indicating severe oxidative stress. Morphological changes in 3rd individuals included decreased brush borders in enterocytes and reduced lipid vacuoles in trophocytes, essential fat bodies for insect metabolism. Immunostaining revealed elevated cleaved caspase 3, an apoptosis marker. This evidence validates the impact of oxidative stress toxicity and cell apoptosis following exposure, offering insights into comprehending the chemically induced effects of oxidative stress by AAPH on animal development., Competing Interests: Declaration of Competing Interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alzheimer's disease (AD) is considered the leading cause of dementia in the elderly worldwide. It results in progressive memory loss and impairment of cognitive and motor skills, leading to a high degree of disability and dependence. The development of AD is associated with the accumulation of senile plaques in the brain, caused by the amyloidogenic pathway of the disease. Several genetic and biochemical events are linked to AD development, with oxidative stress being one of them. Due to the scarcity of drugs aimed at treating AD, antioxidant compounds are increasingly studied as therapeutic targets for the disease. In this study, we investigate the antioxidant and anti-Alzheimer potential of the Tetragonisca angustula (Jataí) pollen extract in a Drosophila melanogaster Alzheimer's model. For this purpose, we utilized a D. melanogaster AD-like model, which expresses genes related to the amyloidogenic pathway of Alzheimer's disease. We explored the floral origin of the collected pollen, conducted phytochemical prospecting, and evaluated its antioxidant capacity in vitro. In vivo experiments involved assessing the survival and climbing ability of the D. melanogaster AD-like model with various concentrations of the pollen extract. Our findings revealed that the pollen extract of Tetragonisca angustula exhibits a significant antioxidant response and high concentrations of important phytochemicals, such as flavonoids and polyphenols. Furthermore, it enhanced the survival rate of D. melanogaster, and across all concentrations tested, it improved the climbing ability of the flies after 15 days of treatment with methanolic pollen extract. Additionally, the pollen extract reduced the neurodegeneration index in histopathological analysis. Thus, our study demonstrates the potential of Tetragonisca angustula pollen as an important subject for further investigation, aiming to isolate molecules that could potentially serve as therapeutic targets for Alzheimer's disease., (© 2024. The Author(s).)

Supplements and diets containing L-leucine, a branched-chain amino acid, have been considered beneficial for controlling oxidative stress and maintaining cardiac tissue in toxicity models using doxorubicin, a drug widely used in cancer treatment. However, there is a lack of studies in the literature that assess the effects of this diet on other organs and tissues, such as the liver and kidneys. Therefore, this study aimed to evaluate the effects of a leucine-rich diet on the liver and kidneys of healthy rats submitted to the doxorubicin toxicity model by analyzing biomarkers of oxidative stress and histological parameters. The animals were divided into four groups: naive, doxorubicin, L-leucine, and doxorubicin + L-leucine, and the diet was standardized with 5% L-leucine and a dose of 7.5 mg/kg of doxorubicin. We evaluated tissue injury parameters and biomarkers of oxidative stress, including enzymes, antioxidant profile, and oxidized molecules, in the liver and kidneys. Although some studies have indicated benefits of a diet rich in L-leucine for the muscle tissue of animals that received doxorubicin, our results showed that the liver was the most affected organ by the L-leucine-rich diet since the diet reduced its antioxidant defenses and increased the deposit of collagen and fat in the hepatic tissue. In the kidneys, the main alteration was the reduction in the number of glomeruli. These results contribute to the scientific literature and encourage further studies to evaluate the effects of an L-leucine-rich diet or its supplementation, alone or combined with doxorubicin using an animal model of cancer. Therefore, our study concludes that the leucine-rich diet itself was harmful and, when co-administered with doxorubicin, was not able to maintain the antioxidant defenses and tissue structure of the evaluated organs.

Learning to anticipate events based on the predictive relationship between an action and an outcome (operant conditioning) is a form of associative learning shared by humans and most of other living beings, including invertebrates. Several behavioral studies on the mechanisms of operant conditioning have included Melipona quadrifasciata, a honey bee that is easily manipulated due to lack of sting. In this work, brain proteomes of Melipona bees trained using operant conditioning and untrained (control) bees were compared by two-dimensional gel electrophoresis analysis within pI range of 3-10 and 4-7; in order to find proteins specifically related to this type of associative learning.One protein was detected with differential protein abundance in the brains of trained bees, when compared to not trained ones, through computational gel imaging and statistical analysis. This protein was identified by peptide mass fingerprinting and MS/MS peptide fragmentation using a MALDI-TOF/TOF mass spectrometer as one isoform of arginine kinase monomer, apparently dephosphorylated. Brain protein maps were obtained by 2-DE (Two-dimensional gel electrophoresis) from a total proteins and phosphoproteins extract of the bee Melipona quadrifasciata. One isoform of arginine kinase, probably a dephosphorylated isoform, was significantly more abundant in the brain of trained bees using operant conditioning. Arginine kinase has been reported as an important enzyme of the energy releasing process in the visual system of the bee, but it may carry out additional and unexpected functions in the bee brain for learning process.

This study reports the isolation of CollinLAAO-I, a new L-amino acid oxidase from Crotalus durissus collilineatus snake venom, its biochemical characterization and leishmanicidal potential in Leishmania spp. CollinLAAO-I (63.1 kDa) was successfully isolated with high purity using two chromatographic steps and represents 2.5% of total venom proteins. CollinLAAO-I displayed high enzymatic activity (4262.83 U/mg/min), significantly reducing after 28 days. The enzymatic activity of CollinLAAO-I revealed higher affinity for hydrophobic amino acids such as L-leucine, high enzymatic activity in a wide pH range (6.0-10.0), at temperatures from 0 to 25 °C, and showed complete inhibition in the presence of Na + and K + . Cytotoxicity assays revealed IC 50 of 18.49 and 11.66 μg/mL for Leishmania (L.) amazonensis and Leishmania (L.) infantum, respectively, and the cytotoxicity was completely suppressed by catalase. CollinLAAO-I significantly increased the intracellular concentration of reactive oxygen species (ROS) and reduced the mitochondrial potential of both Leishmania species. Furthermore, CollinLAAO-I decreased the parasite capacity to infect macrophages by around 70%, indicating that even subtoxic concentrations of CollinLAAO-I can interfere with Leishmania vital processes. Thus, the results obtained for CollinLAAO-I provide important support for developing therapeutic strategies against leishmaniasis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Dyslipidemia and oxidative stress are directly related to the pathogenesis of cardiovascular diseases. Annona crassiflora Mart. (ACM) has been traditionally used in folk medicine to alleviate inflammation and pain. This plant is rich in polyphenols, which exhibit high antioxidant capacity. The present study aimed to elucidate the antioxidant properties of ACM in the heart of hyperlipidemic mice. The animals were orally administered either a crude ethanol extract (CEAc) or a polyphenols-rich fraction (PFAc) obtained from ACM fruit peel. There were correlations between blood and fecal biochemical data with cardiac oxidative stress biomarkers. Here, the pre-treatment with CEAc for 12 d led to an increase in glutathione content (GSH) and a reduction in the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase. Moreover, PFAc was found to enhance the total antioxidant capacity as well as GSH, SOD and CAT activities, which were reduced by Triton WR-1339-induced hyperlipidemia. Moreover, the administration of PFAc before the treatment resulted in a decrease in protein carbonylation and lipid peroxidation levels, as well as a reduction in the activities of glutathione reductase and glucose-6-phosphate dehydrogenase. ACM fruit peel showed improvement in the glutathione system, mainly its polyphenols-rich fraction, indicating a potential cardioprotective antioxidant usage of this plant extract.

Background: The motivations for and effects of ethanol consumption vary considerably among individuals, and as such, a significant proportion of the population is prone to substance abuse and its negative consequences in the physical, social, and psychological spheres. In a biological context, the characterization of these phenotypes provides clues for understanding the neurological complexity associated with ethanol abuse behavior. Therefore, the objective of this research was to characterize four ethanol preference phenotypes described in zebrafish: Light, Heavy, Inflexible, and Negative Reinforcement., Methods: To do this, we evaluated the telomere length, mtDNA copy number using real-time quantitative PCR (qPCR), and the activity of these antioxidant enzymes: catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the brain, and the interactions between these biomarkers. Changes observed in these parameters were associated with ethanol consumption and alcohol abuse., Results: The Heavy, Inflexible, and Negative Reinforcement phenotypes showed ethanol preference. This was particularly the case with the Inflexible phenotype, which was the group with the greatest ethanol preference. These three phenotypes showed telomere shortening as well as high SOD/CAT and/or GPx activities, while the Heavy phenotype also showed an increase in the mtDNA copy number. However, the Light phenotype, containing individuals without ethanol preference, did not demonstrate any changes in the analyzed parameters even after being exposed to the drug. Additionally, the PCA analysis showed a tendency to cluster the Light and Control groups differently from the other ethanol preference phenotypes. There was also a negative correlation between the results of the relative telomere length and SOD and CAT activity, providing further evidence of the biological relationship between these parameters., Conclusions: Our results showed differential molecular and biochemistry patterns in individuals with ethanol preference, suggesting that the molecular and biochemical basis of alcohol abuse behavior extends beyond its harmful physiological effects, but rather is correlated with preference phenotypes., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

The blood diagnosis of diabetes mellitus (DM) is highly accurate; however, it is an invasive, high-cost, and painful procedure. In this context, the combination of ATR-FTIR spectroscopy and machine learning techniques in other biological samples has been used as an alternative tool to develop a non-invasive, fast, inexpensive, and label-free diagnostic or screening platform for several diseases, including DM. In this study, we used the ATR-FTIR tool associated with linear discriminant analysis (LDA) and a support vector machine (SVM) classifier in order to identify changes in salivary components to be used as alternative biomarkers for the diagnosis of type 2 DM. The band area values of 2962 cm -1 , 1641 cm -1 , and 1073 cm -1 were higher in type 2 diabetic patients than in non-diabetic subjects. The best classification of salivary infrared spectra was by SVM, showing a sensitivity of 93.3% (42/45), specificity of 74% (17/23), and accuracy of 87% between non-diabetic subjects and uncontrolled type 2 DM patients. The SHAP features of infrared spectra indicate the main salivary vibrational modes of lipids and proteins that are responsible for discriminating DM patients. In summary, these data highlight the potential of ATR-FTIR platforms coupled with machine learning as a reagent-free, non-invasive, and highly sensitive tool for screening and monitoring diabetic patients.

The development of novel platforms for non-invasive continuous glucose monitoring applied in the screening and monitoring of diabetes is crucial to improve diabetes surveillance systems. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy of urine can be an alternative as a sustainable, label-free, fast, non-invasive, and highly sensitive analysis to detect changes in urine promoted by diabetes and insulin treatment. In this study, we used ATR-FTIR to evaluate the urinary components of non-diabetic (ND), diabetic (D), and diabetic insulin-treated (D + I) rats. As expected, insulin treatment was capable to revert changes in glycemia, 24-h urine collection volume, urine creatinine, urea, and glucose excretion promoted by diabetes. Several differences in the urine spectra of ND, D, and D + I were observed, with urea, creatinine, and glucose analytes being related to these changes. Principal components analysis (PCA) scores plots allowed for the discrimination of ND and D + I from D with an accuracy of ∼ 99 %. The PCA loadings associated with PC1 confirmed the importance of urea and glucose vibrational modes for this discrimination. Univariate analysis of second derivative spectra showed a high correlation (r: 0.865, p < 0.0001) between the height of 1074 cm-1 vibrational mode with urinary glucose concentration. In order to estimate the amount of glucose present in the infrared spectra from urine, multivariate curve resolution-alternating least square (MCR-ALS) was applied and a higher predicted concentration of glucose in the urine was observed with a correlation of 78.9 % compared to urinary glucose concentration assessed using enzyme assays. In summary, ATR-FTIR combined with univariate and multivariate chemometric analyses provides an innovative, non-invasive, and sustainable approach to diabetes surveillance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Chronically elevated alpha-2-macroglobulin (A2MG) in the blood has been correlated with diabetes and the HbA1c profile; however, no systematic review has been conducted to evaluate the association of A2MG salivary levels and glycemia or HbA1c levels in diabetes mellitus type 2 (DM2) patients., Objective: To evaluate whether A2MG salivary levels are related to the glycemia or HbA1c levels in DM2 patients., Design and Setting: Systematic review developed at Universidade Federal de Uberlândia (UFU), Brazil., Methods: Eight databases were used as research sources. The eligibility criteria included studies that reported data regarding mean salivary A2MG and the correlation between glycemia and/or HbA1c levels of DM2 subjects (uncontrolled and well-controlled) and non-diabetic subjects. The risk of bias of the studies selected was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools for use in JBI systematic reviews. Pooled correlation coefficients were estimated using the Hunter-Schmidt method. Study estimates were weighted according to their sample size, and heterogeneity was calculated using the chi-square statistic., Results: Four studies on DM2 patients were included in this systematic review after careful analysis of 1482 studies. Three studies compared A2MG with HbA1c and glycemia. Overall, the correlation between A2MG and HbA1c was strong (r = 0.838). In contrast, the correlation between A2MG and glycemia was low (r = 0.354)., Conclusion: The strong association between HbA1C and salivary A2MG suggests that this salivary protein has the potential to be a surrogate for HbA1C, if corroboratory further evidence is obtained through large-scale studies.

Objective: This study aimed (i) to evaluate the antibacterial and cytotoxic activities of the crude extract and fractions obtained from Euclea natalensis A.D.C. roots against bacteria that cause periodontal disease and caries and (ii) to identify the isolated compounds., Design: The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of the extract and fractions were determined by the microplate dilution assay. The cytotoxicity of the extract and fractions was evaluated by using the XTT colorimetric assay and normal human fibroblast cells (GM07492A, lung fibroblasts). The compounds present in the most promising fraction were determined by qualitative analysis through liquid chromatography coupled to mass spectrometry (HPLC-MS-ESI)., Results: The MIC results ranged from 25 to > 400 μg/mL for the extract and from 1.56 to > 400 μg/mL for the fractions. To evaluate cytotoxicity, the tested concentrations of the extract and fractions ranged from 19.5 to 2500 μg/mL; IC 50 values between 625 and 1250 μg/mL were obtained. Analysis of the main bioactive fraction by HPLC-MS-ESI identified phenolic acids, coumarins, naphthoquinones, lignans, and fatty acids., Conclusions: The E. natalensis root extract and fractions displayed good antibacterial activity against periodontal pathogenic and cariogenic bacteria. The antibacterial activity may be due to compounds present in the extract and fractions, which also showed low cytotoxicity to normal human cells. These data are relevant and encourage further research into this plant species, which may contribute to the discovery of new herbal medicines that will help to mitigate the problems caused by oral pathogenic bacteria., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Postmenopausal women have a high prevalence of cardiometabolic diseases and that may associate with higher oxidative stress. Exercise can contribute to the treatment of such diseases, but some modalities, such as Mat Pilates, need to be further studied in terms of their physiological responses. Our aim was to investigate the effects of 12 weeks of Mat Pilates on redox status in postmenopausal women with one or multiple comorbidities of cardiometabolic diseases. Forty-four postmenopausal women were divided into two groups: SINGLE, composed of women with one cardiometabolic disease ( n = 20) and MULT, with multimorbidity ( n = 24). Mat Pilates training was conducted three times a week for 12 weeks, and each session lasted 50 min. Plasma samples were collected before and after training to analyze the following redox markers: superoxide dismutase, catalase, glutathione peroxidase, total antioxidant capacity due to ferric-reducing antioxidant power (FRAP), reduced glutathione (GSH), uric acid, and carbonyl protein. ANCOVA showed interaction effects in FRAP ( p = 0.014). Both groups had reduced levels of catalase ( p = 0.240) and GSH ( p = 0.309), and increased levels of carbonyl protein ( p = 0.053) after intervention. In conclusion, the redox status of postmenopausal women shows no changes mediated by Mat Pilates training between SINGLE and MULT, except for greater reductions of FRAP in SINGLE.

Wounds treated with TiO2 nanoparticles (TiO2-NPs) show an improvement in healing time. However, little is known about the parameters that can contribute to this result. On the other hand, the treatment of wounds with polyphenols is widely known. These compounds are found in the peel of Annona crassiflora fruit and have antioxidant, analgesic and anti-inflammatory properties. In this study, we evaluated the healing effect of TiO2 nanocrystals (TiO2-NCs), polyphenolic fractions obtained from ethanolic extract of A. crassiflora fruit peel (PFAC) and mix (PFAC + TiO2-NCs) on the parameters of wound closure, inflammation, collagen deposition, metalloproteinase activity (MMPs) and angiogenesis. TiO2-NCs and PFAC have activity for wound healing, showed anti-inflammatory action and a shorter wound closure time. These treatments also contributed to increased collagen deposition, while only treatment with TiO2-NCs increased MMP-2 activity, parameters essential for the migration of keratinocytes and for complete restoration of the injured tissue. The combination of PFAC + TiO2-NCs reduced the effectiveness of individual treatments by intensifying the inflammatory process, in addition to delaying wound closure. We conclude that the interaction between the hydroxyl groups of PFAC polyphenols with TiO2-NCs may have contributed to difference in the healing activity of skin wounds.

Alzheimer's disease (AD) is the most common form of dementia in the elderly, affecting cognitive, intellectual, and motor functions. Different hypotheses explain AD's mechanism, such as the amyloidogenic hypothesis. Moreover, this disease is multifactorial, and several studies have shown that gut dysbiosis and oxidative stress influence its pathogenesis. Knowing that kefir is a probiotic used in therapies to restore dysbiosis and that the bioactive peptides present in it have antioxidant properties, we explored its biotechnological potential as a source of molecules capable of modulating the amyloidogenic pathway and reducing oxidative stress, contributing to the treatment of AD. For that, we used Drosophila melanogaster model for AD (AD-like flies). Identification of bioactive peptides in the kefir sample was made by proteomic and peptidomic analyses, followed by in vitro evaluation of antioxidant and acetylcholinesterase inhibition potential. Flies were treated and their motor performance, brain morphology, and oxidative stress evaluated. Finally, we performed molecular docking between the peptides found and the main pathology-related proteins in the flies. The results showed that the fraction with the higher peptide concentration was positive for the parameters evaluated. In conclusion, these results revealed these kefir peptide-rich fractions have therapeutic potential for AD., (© 2022. The Author(s).)

The biological applicability of nanomaterials has been limited due to cytotoxicity. Studies have described the effects of nanomaterials on different tissues and cell types, but their actions on immune cells are less elucidated. This study describes unprecedented in vitro and in vivo antioxidant activities of cadmium selenide magic-sized quantum dots (CdSe MSQDs) with implications on rheumatoid arthritis. While the generation of ROS induced by nanomaterials is linked to cytotoxicity, we found that CdSe MSQDs reduced ROS production by neutrophils and macrophages following opsonized-zymosan stimuli, and we did not find cytotoxic effects. Interestingly, inherent antioxidant properties of CdSe MSQDs were confirmed through DPPH, FRAP, and ORAC assays. Furthermore, CdSe MSQDs reduced ROS levels generated by infiltrating leukocytes into joints in experimental model of rheumatoid arthritis. Briefly, we describe a novel application of CdSe MSQDs in modulating the inflammatory response in experimental rheumatoid arthritis through an unexpected antioxidant activity., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Annona muricata Linn. is a common plant found in the warmest regions of South and Central America and its use in traditional medicine has been reported for the treatment of various illnesses. In the current study, we investigate the antioxidant and anti-inflammatory activities of crude extract and fractions from A. muricata L. leaves in isolated murine phagocytic immune cells as well as experimental LPS-induced acute lung injury (ALI). In a luminol-dependent chemiluminescence assay, we showed that ethyl acetate (EtOAc.f) and n-butanol (BuOH.f) fractions-both rich in polyphenols-reduced the generation of reactive oxygen species (ROS) by neutrophils stimulated with opsonized zymosan; similar results were found in culture of bone marrow-derived macrophages (BMDMs). By evaluating anti-inflammatory activity in BMDMs, EtOAc.f and BuOH.f reduced secretion of IL-6 and expression of the co-stimulatory molecule CD40. Furthermore, in LPS-induced ALI, oral administration of EtOAc.f reduced myeloperoxidase (MPO) activity in lung tissue. In addition, on a mechanism dependent on glutathione levels, the oxidative damage was also attenuated. These findings revealed direct antioxidant and anti-inflammatory activities of polyphenols-rich fractions of A. muricata L. leaves on neutrophils and macrophages. Moreover, the reduced oxidative damage and levels of inflammatory markers in experimental ALI suggest that these fractions might be explored for the development of new therapies for inflammatory conditions.

The enzyme heme oxygenase-1 (HO-1) has cytoprotective effects by catalyzing the degradation of heme to produce carbon monoxide, iron and biliverdin. Furthermore, HO-1 activity has been associated with successful pregnancy. On the other hand, in the context of certain inflammatory conditions, HO-1 can induce iron overload and cell death. To investigate the role of HO-1 in gestational malaria, pregnant BALB/c mice were infected with Plasmodium berghei ANKA in early, mid and late gestation. We found that malaria affected the pregnancy outcome in the three periods evaluated. However, only poor pregnancy outcomes in early pregnancy were related to HO-1 upregulation, iron overload, lipid peroxidation and necrosis of the decidua, which were prevented by HO-1 inhibition. In conclusion, HO-1 expression must be finely tuned in gestational malaria to avoid the deleterious effect of increased enzyme activity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cariaco, Almeida, Araujo, Briceño, Durán-Rodriguez, Franco, Espindola and Silva.)

CdSe magic-sized quantum dots (MSQDs) have been widely used as fluorescent probes in biological systems due to their excellent optical properties with a broader fluorescence spectrum and stable luminescence in biological media. However, they can be cytotoxic and alter the redox balance depending on the amounts of Cd 2+ adsorbed on their surface. Thus, the present study aimed to evaluate whether increases in selenium concentration in the synthesis of CdSe-MSQDs decrease the oxidative stress caused by Cd 2+ -based quantum dots. CdSe-MSQDs synthesized with different concentrations of selenium were investigated against oxidative stress in the brain of chicken embryos by examining total antioxidant capacity, lipid peroxidation, thiol, and glutathione contents, as well as the activities of glutathione peroxidase, superoxide dismutase (SOD), catalase (CAT), and glutathione reductase. In addition, the vascularization of the chorioallantoic membrane (CAM) analysis was performed. Higher selenium concentrations alter the surface defect levels (decrease free Cd 2+ ) and controlled the oxidative effects of CdSe-MSQDs by reducing the lipid peroxidation, restoring the glutathione defense system and the antioxidant enzymes SOD and CAT, and maintaining the vascular density of the CAM. The current findings reinforce the study of the effects of the presence of Cd 2+ ions on the surface of quantum dots, changing toxicity, and aiming interesting strategies of nanomaterials in biological systems., (© 2021 Wiley Periodicals LLC.)

Several studies have been developed using the Gallus gallus embryo as an experimental model to study the toxicity of drugs and infections. Studies that seek to standardize the evaluated parameters are needed to better understand and identify the viability of CEs as an experimental model. Therefore, we sought to verify whether macroscopic, histopathological, blood count, metabolites and/or enzymes changes and oxidative stress in CE of different ages are specific to the model. To achieve this goal, in ovo assays were performed by injecting a virus ( Gammacoronavirus ) and two drugs (filgrastim and dexamethasone) that cause known changes in adult animals. Although congestion and inflammatory infiltrate were visible in the case of viral infections, the white blood cell count and inflammation biomarkers did not change. Filgrastim (FG) testing did not increase granulocytes as we expected. On the other hand, CE weight and red blood cell count were lower with dexamethasone (DX), whereas white blood cell count and biomarkers varied depended on the stage of CE development. Our work reinforces the importance of standardization and correct use of the model so that the results of infection, toxicity and pharmacokinetics are reproducible.

Annona crassiflora Mart. is a species native to the Cerrado biome, whose fruit is known as araticum or marolo. Plant parts are widely used in folk medicine to treat inflammation and pain associated with rheumatism, wounds, venereal diseases, snakebites, and microbial infections. Thus, we investigated a fraction rich in phenolic compounds (PCAc) obtained from the crude extract of the peel of these fruits on non-cytotoxic, anti-inflammatory, antioxidant, and collagen biosynthesis properties in the healing of wounds induced on the back of BALB/c mice. For the control group, the induced wounds were not treated and for the others, wounds were treated topically with vehicle or vehicle plus PCAc. Both fractions contained in PCAc demonstrated effective protection on fibroblasts. We highlight the effect of the ethyl acetate fraction which, in addition to the protective effect, has a proliferative activity on these cells. In addition, PCAc caused improvement in healing after 7 days of treatment and in the longest period of treatment with PCAc (7, 14, and 21 days) there was a greater contraction of the wound, accompanied by resolution of the inflammatory process, antioxidant defense, increasing collagen synthesis, and modulation of metalloproteinases. PCAc demonstrated better re-epithelialization and organization of the dermis at the end of treatment. The changes promoted by the phenolic compounds of A. crassiflora were important in the healing process, especially in activities related to inflammation, oxidative stress, and fibrogenesis., Competing Interests: Declaration of Competing Interest The authors declare no competing interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Ethnopharmacological Relevance: Different parts of Eugenia dysenterica have been popularly used in Brazil for treating diabetes mellitus and its complications. The present study aimed to screen extracts from E. dysenterica fruit pulp, peel, seed and leaf for carbohydrate digestive enzymes inhibitors with antioxidant and anti-glycation capacities., Materials and Methods: Ethanol extracts of E. dysenterica were subjected to a liquid-liquid fractionation and the fractions were used to evaluate their antioxidant properties and inhibitory potential against the formation of advanced glycation end-products (AGEs) and α-amylase and α-glucosidase., Results: The ethyl acetate fraction (EtOAcF) from seed and the dichloromethane fraction (CH 2 Cl 2 F) and EtOAcF from leaf had high antioxidant capacities (ORAC >5500 μmol trolox eq g -1 , FRAP >1500 μmol trolox eq g -1 and DPPH IC 50  < 35 μg mL -1 ) and showed exceptional inhibitory activities against AGEs formation (glycation inhibition above 80% at 10 μg mL -1 ) and α-amylase and α-glucosidase (inhibition above 50% at 10 μg mL -1 ). The gallated B-types proanthocyanidins were the most active ingredients found in the leaf of E. dysenterica (CH 2 Cl 2 and EtOAcF), being responsible for the notorious inhibitory effects against glycation and glycoside hydrolases due to their ortho-hydroxyl groups, which play role in scavenge and quench free radicals and glycated products, and may occupy the enzymes' substrate binding pocket. Furthermore, gallic acid, quercetin and its glycoside derivatives were detected by the first time in the E. dysenterica fruit seed (EtOAcF)., Conclusions: The results strongly contribute to the understanding of the antidiabetic potential of seeds and leaves from E. dysenterica, a species from a global biodiversity hotspot, which appears to be linked to the prevention of oxidative stress, AGEs production and postprandial hyperglycemia., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Chronic hyperglycemia and hyperlipidemia are associated with excessive formation of reactive oxygen species and advanced glycation end-products. The present study aimed to evaluate the potential in vitro antidiabetic properties of Kielmeyera coriacea inner bark. The main phytochemical compounds were identified by UHPLC-ESI/MS n and the ethanol extract and its fractions were used to evaluate their antioxidant and anti-glycation capacities, as well as their inhibitory potential against glycoside and lipid hydrolases activities. The polar fractions, especially the n-butanol fraction, had free radical scavenging and quenching properties (ORAC and FRAP values>1800 and 1000 µmol trolox eq/g, respectively, and DPPH IC 50 <4 µg/mL), and inhibited ROS production (p < 0.01), lipid peroxidation (p < 0.001), glycation (IC 50 ~ 10 µg/mL in the BSA-fructose assay; IC 50 ~ 200 µg/mL in the BSA-methylglyoxal and arginine-methylglyoxal assays), α-amylase (IC 50 <0.1 µg/mL) and lipase (IC 50 <5 µg/mL), with no cytotoxicity. Biomolecules well-known as potent antioxidants were identified for the first time in the inner bark of K. coriacea, such as protocatechuic acid, epicatechin and procyanidins A, B and C. Together, our results support the antioxidant, anti-glycation and glycoside and lipid hydrolases inhibitory properties of the inner bark of K. coriacea, a species found in the Brazilian savanna, which makes it especially useful to combat oxidative stress and hyperglycemia and hyperlipidemia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Dyslipidemia is a risk factor for the pathogenesis of several diseases, such as obesity, hypertension, atherosclerosis and cardiovascular diseases. In addition to interfering with serum concentrations of cholesterol and triglycerides, hyperlipidemia is involved in oxidative stress increase and reduction of the endogenous antioxidant defenses. The fruit peel of Annona crassiflora crude extract (CEAc) and its polyphenols-rich fraction (PFAc) were investigated against hypertriglyceridemia, hypercholesterolemia and hepatic oxidative stress in Triton WR-1339-induced hyperlipidemic mice. Lipid parameters in serum, feces and liver, as well as hepatic oxidative status, and enzymatic and non-enzymatic antioxidant defense systems were analyzed. Pre-treatment with CEAc for 12 days decreased hepatic triglycerides and total cholesterol, and similar to PFAc, increased the high-density lipoprotein level. There were reductions in lipid peroxidation and protein carbonylation, as well as restoration of the glutathione defense system and total thiol content in the liver of the hyperlipidemic mice treated with PFAc. The fruit peel of A. crassiflora, a promising natural source of bioactive molecules, showed a potential lipid-lowering action and hepatoprotective activities triggered by reduction of oxidative damage and maintenance of the enzymatic and non-enzymatic antioxidant systems impaired by the hyperlipidemic state., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: to assess if changes in salivary alpha-amylase activity are associated with anxiety and stress among hospital nursing professionals and whether anxiety and stress are associated with sociodemographic, epidemiological, and occupational factors., Method: cross-sectional, quantitative study, carried out with 210 nursing professionals from a hospital. For data collection, we used a questionnaire to characterize workers, Beck's Anxiety Inventory, Lipp's Stress Symptoms Inventory for Adults and samples and saliva samples collected in work shifts. The data were analyzed descriptively and inferentially using the software Statistical Package for the Social Science and GraphPad Prism., Results: most professionals experienced stress and anxiety. The variables age group, number of children, use of medication and workload were associated with anxiety; age group, smoking and medication use were associated with stress. An increase in the salivary alpha-amylase activity was observed in the middle of the work shift. Professionals who had stress and anxiety had significant changes in alpha-amylase in the night shift., Conclusion: changes in salivary alpha-amylase were associated with anxiety and stress among nursing professionals, indicating that this enzyme can be a possible biomarker of anxiety and stress in workers.

Ethnopharmacological Relevance: Sulfadiazine and pyrimethamine are the two drugs used as part of the standard therapy for toxoplasmosis, however; they may cause adverse side effects and fail to prevent relapse in many patients, rendering infected individuals at risk of reactivation upon becoming immunocompromised. Extracts from various parts of Annona muricata have been widely used medicinally for the management, control and/or treatment of several human diseases, acting against parasites that cause diseases in humans., Aim of the Study: This study was performed to investigate the action of the ethanolic extract of A. muricata (EtOHAm) and its fractions in the control of the apicomplexan parasite Toxoplasma gondii in vitro and in vivo, and the effect of EtOHAm on the inflammatory response and lipid profile alteration induced by in vivo T. gondii infection., Materials and Methods: The cytotoxicity of EtOHAm and its fractions ethyl acetate (EtOAcAm), n-butanol (BuOHAm), aqueous (H 2 OAm), hexane (HexAm) and dichloromethane (CH 2 Cl 2 Am) was evaluated in NIH/3T3 fibroblasts using the (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The cells were infected with T. gondii, treated with the extracts, and parasite proliferation was analyzed. For the in vivo experiments, C57BL/6 mice were orally infected with T. gondii and, treated with different concentrations of extract fractions that were effective in vitro (EtOHAm, EtOAcAm, HexAm and CH 2 Cl 2 Am). Tissue parasitism, histological alterations, systemic cytokine and lipid profile were investigated., Results: EtOHAm, EtOAcAm, BuOHAm, H 2 OAm presented low cytotoxicity until doses of 200 μg/mL, while HexAm and CH 2 Cl 2 Am presented toxicity from doses of 100μg/mL. EtOHAm, HexAm and CH 2 Cl 2 Am decreased the parasitism in vitro, presenting a therapeutic index of 2.62, 2.44, and 2.96, respectively. In vivo, EtOHAm, HexAm and CH 2 Cl 2 Am improved the survival rate of infected animals, however, only EtOHAm was able to decrease the parasitism in the small intestine and lung. Additionally, EtOHAm decreased the systemic interferon (IFN)-γ and tumor necrosis factor (TNF) systemically in infected mice, and was able to maintain the triglycerides and very-low-density lipoprotein (VLDL) lipid fractions at similar levels to uninfected animals. Although treatment with EtOHAm could not control the inflammation induced by oral infection in the tissues analyzed, it was able to preserve the number of goblet cells in the small intestine., Conclusions: Ethanolic A. muricata leaf extract could be considered as a good candidate for the development of a complementary/alternative therapy against toxoplasmosis, and also as an anti-inflammatory alternative for decreasing TNF and IFN-γ concentrations and lipid fractions in specific diseases., (Copyright © 2021 Elsevier B.V. All rights reserved.)

(1) Background: Nanocrystals (NCs)-based electrochemical sensors have been proposed for biomarkers detection, although immunosensors using ZnO NCs decorated with copper are still scarce. (2) Methods: Electrochemical immunodetection of human salivary alpha-amylase (HSA) used ZnO, CuO, and ZnO:xCu (x = 0.1, 0.4, 1.0, 4.0, and 12.0) NCs. (3) Results: Substitutional incorporation of Cu 2+ in the crystalline structure of ZnO and formation of nanocomposite were demonstrated by characterization. Graphite electrodes were used and the electrochemical signal increased by 40% when using ZnO:1Cu and 4Cu (0.25 mg·mL -1 ), in an immunosensor (0.372 mg·mL -1 of anti-alpha-amylase and 1% of casein). Different interactions of HSA with the alpha-amylase antibody were registered when adding the NCs together, either before or after the addition of saliva (4 μL). The immunosensor changed specificity due to the interaction of copper. The ZnO:1Cu and ZnO:4Cu samples showed 50% interference in detection when used before the addition of saliva. The immunosensor showed 100% specificity and a sensitivity of 0.00196 U·mL -1 . (4) Conclusions: Results showed that the order of NCs addition in the sensors should be tested and evaluated to avoid misinterpretation in detection and to enable advances in the validation of the immunosensor.

Alzheimer's Disease (AD) is the most common cause of dementia among elderly individuals worldwide, leading to a strong motor-cognitive decline and consequent emotional distress and codependence. It is traditionally characterized by amyloidogenic pathway formation of senile plaques, and recent studies indicate that dysbiosis is also an important factor in AD's pathology. To overcome dysbiosis, probiotics-as kefir-have shown to be a great therapeutic alternative for Alzheimer's disease. In this present work, we explored kefir as a probiotic and a metabolite source as a modulator of microbiome and amyloidogenic pathway, using a Drosophila melanogaster model for AD (AD-like flies). Kefir microbiota composition was determined through 16S rRNA sequencing, and the metabolome of each fraction (hexane, dichloromethane, ethyl acetate, and n-butanol) was investigated. After treatment, flies had their survival, climbing ability, and vacuolar lesions accessed. Kefir and fraction treated flies improved their climbing ability survival rate and neurodegeneration index. In conclusion, we show that kefir in natura, as well as its fractions may be promising therapeutic source against AD, modulating amyloidogenic related pathways.

Background and Aim: Maytenus ilicifolia has analgesic, healing, antioxidant and anti-inflammatory properties. This study evaluated effect of the hydroalcoholic extract of M. ilicifolia leaves on skin wound repair., Experimental Procedure: Wounds were induced on mice and treated with the extract. The treatment was performed daily, until day 7 after wound induction. Wound closure was measured and the features of the repaired tissue were investigated, including mast cell quantification, neutrophil and macrophage activities, collagen deposition, angiogenesis, and pro-metalloproteases and metalloproteases 2 and 9 activity (pro-MMPs and MMPs)., Results and Conclusion: The M. ilicifolia extract accelerated the closure of wounds. The extract at a concentration of 4% was found to be effective, presenting anti-inflammatory effects and hemoglobin increased, along with increased soluble, total and type III collagens in the wound. In addition, there was an increase in pro-MMP9 and MMP9 activity after day 7th of treatment. The phenolic compounds and tannins present in this plant could be associated with the anti-inflammatory and healing activities observed in this study. Therefore, the ability to modulate essential parameters for accelerated and adequate healing as shown here suggests that the use of standardised extracts of M. ilicifolia and its fractions enriched in polyphenols may represent a therapeutic strategy for the treatment of wounds., Competing Interests: The authors declare that they have no competing interests., (© 2021 Center for Food and Biomolecules, National Taiwan University. Production and hosting by Elsevier Taiwan LLC.)

Ethnopharmacological Relevance: The substantial increase in diabetes cases worldwide has been a major public health problem, and the use of medicinal plants can be considered an interesting alternative to control the disease and its complications. Anacardium humile St. Hill. (Anacardiaceae) is a typical plant from the Brazilian savanna, popularly known for its antidiarrheal, expectorant, antidiabetic and anti-inflammatory properties, however, few studies have fully described its biological properties. This study aimed to investigate in vitro and ex vivo the antioxidant and antiglycation potential of A. humile ethanolic extract, its organic fractions and three isolated molecules (quercetin, catechin and gallic acid), their capacity to inhibit the glycolytic enzyme α-amylase, as well as their cytotoxic effects against RAW264.7 macrophages., Material and Methods: The ethanolic extract of A. humile, its organic fractions and three isolated molecules (catechin, quercetin and gallic acid) were tested for their antioxidant (ORAC, FRAP and DPPH) and antiglycation (BSA/Fructose, BSA/Methylglyoxal, Arginine/Methylglyoxal and Lysine/Methylglyoxal) capacities, and also for its potential to inhibit the enzyme α-amylase. Additionally, bioactive compounds present in the A. humile leaves fractions were elucidated by an HPLC-ESIMS/MS analysis., Results: The analysis showed relevant antioxidant activity of DCM (1264.85 ± 76.90 μM Trolox eq/g ORAC; 216.71 ± 1.04 μM Trolox eq/g FRAP and 3.03 ± 0.08 IC 50 μg/mL IC 50 DPPH) and EtOAc (1300.11 ± 33.04 ORAC, 236.21 ± 23.86 FRAP and 3.03 ± 0.14 μg/mL IC 50 DPPH) fractions and also of the isolated molecules, mainly gallic acid (1291.19 ± 8.41 μM Trolox eq/g ORAC, 1103.52 ± 31.48 μM Trolox eq/g FRAP and 0.78 ± 0.11 μg/mL IC 50 DPPH). Concerning the antiglycation activity, all samples inhibited over 88% in the BSA-FRU method. In the BSA-MGO and ARG-MGO methods, the Hex, DCM, EtOAc fractions and the isolated molecule catechin stood out. However, in the LYS-MGO model, only the isolated molecules showed significant results. In α-amylase assay, all fractions, for exception Hex, presented notable inhibition capacity with low IC 50 values, especially DCM, EtOAc, ButOH and H 2 O (IC 50 0.56 ± 0.10, 0.84 ± 0.01, 0.74 ± 0.03 and 0.79 ± 0.06 μg/mL, respectively). Tests using hepatic tissue showed a notorious capacity of the DCM, AcOEt and ButOH fractions, as well as of the isolated molecules to inhibit lipid peroxidation and ROS production, and also to preserve thiol groups. Molecules of great antioxidant potential were found in our samples, such as kaempferol, quercetin, catechin, gallic acid and luteolin., Conclusion: A. humile extract and its organic fractions showed promising antioxidant and antiglycation potential and a prominent capacity to inhibit the α-amylase enzyme. Hence, this study presents new results and stimulates further research to elucidate the biological properties of A. humile and its capacity to manage DM and its complications., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Pfaffia glomerata roots are widely used in Brazil to treat various pathological conditions, particularly psychological disorders. 20-hydroxyecdysone, a phytosteroid present in the plant, can promote greater body resistance against exogenous and endogenous stressors. The objective of this study was to evaluate the possible neuroprotective effect of a 20-hydroxyecdysone-enriched fraction (20E-EF), obtained from P. glomerata roots, in an acute murine stress model., Material and Methods: The 20E-EF was obtained by partitioning the methanol extract from P. glomerata roots with dichloromethane. Mice were treated by gavage with three doses of 20E-EF (3, 10, and 30 mg/kg) and parameters of stress, anxiety, and depression were evaluated. Biomarkers of oxidative stress (enzymes, antioxidant profile, and oxidized molecules) were evaluated in the cortex, striatum (basal ganglia), and hippocampus of animals treated with 30 mg/kg of 20E-EF., Results: Mass spectrometry revealed that 20E was the main compound in the dichloromethane fraction. At a dose of 30 mg/kg, 20E-EF reduced stress, anxiety, and depression, while stimulating antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase), promoting antioxidant activity (antioxidant capacity, sulfhydryl groups, and reduced glutathione), and reducing oxidative markers (lipid peroxidation). In addition, 20E increased the concentration of NO in the striatum, possibly improving memory function and antioxidant activity., Conclusion: A 30 mg/kg dose of 20E-EF was able to reduce stress, anxiety, and depression, in addition to maintaining antioxidant defenses of the cortex and striatum. These findings open new perspectives for understanding the therapeutic properties of P. glomerata and the underlying mechanism(s)., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Banisteriopsis argyrophylla belongs to the Malpighiaceae family, which is a species from Cerrado, also known as "cipó-prata" or "cipó-folha-de-prata." Several species of this family present biological potential. This work reports the chemical identification of the ethanol extract (EE) and its fractions from B. argyrophylla leaves and shows the analysis of the antioxidant activity and inhibitory effects on activities of α-amylase, α-glucosidase and lipase, and non-enzymatic glycation. The ethyl acetate fraction (EAF) and n-butanol fraction (BF) showed antioxidant activity, with IC 50 values of 4.1 ± 0.1 and 4.8 ± 0.1 μg mL -1 , respectively, by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, and IC 50 values of 6046.3 ± 174.2 and 6264.2 ± 32.2 µmol Trolox eq g -1 by the oxygen radical absorbance capacity (ORAC) method. Furthermore, the DPPH method with these fractions presented electroactive species with antioxidant potential, as shown by the differential pulse voltammetry (DPV) method. The inhibitory effects of the EAF and BF were demonstrated by the following results: IC 50 of 5.1 ± 0.3 and 2.5 ± 0.2 μg mL -1 for α-amylase, IC 50 of 1093.5 ± 26.0 and 1250.8 ± 21.9 μg mL -1 for α-glucosidase, IC 50 of 8.3 ± 4.1 and 4.4 ± 1.0 μg mL -1 for lipase, and IC 50 of 1.3 ± 0.1 and 0.9 ± 0.1 μg mL -1 for glycation. Some bioactive compounds were identified by (-)-ESI-MS/MS, such as catechin, procyanidins, glycosylated flavonoids, kaempferol, and megastigmane glucosides. The antidiabetic activity of B.argyrophylla has been reported for the first time., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: Plant materials are commonly used in traditional medicine in order to treat various diseases such as Diabetes mellitus. Some plants, such as Syzygium cumini, have the capability to act controlling oxidative stress and protein glycation besides their potential to decrease hyperglycemia and hyperlipidemia by the inhibition of the catalysis of digestive enzymes. The aim of this study was to evaluate the antioxidant and antiglicant activity of S. cumini leaves fractions, their capacity to inhibit hydrolases and lipase enzymes, as well as the cytotoxicity effects against erythrocytes and comparate these results with isolate quercetin flavonoid., Material and Methods: Ethnobotanical researches, carried out by academic studies at the Federal University of Uberlandia, led us to choose S. cumini as a potential plant for treatment of Diabetes mellitus. Fractions from ethanolic extract of S. cumini (hexane/Hex, dichloromethane/DCM, ethyl acetate/EtOAc, n-butanol/ButOH and water/H 2 O) were used to evaluate their antioxidant (DPPH, ORAC and FRAP) and antiglycant (BSA/fructose, BSA/methylglyoxal and Arginine/Methylglyoxal) activity as well as the inhibitory potential against α-amylase, α-glucosidase and lipase. In addition, identification of the main bioactive compounds of S. cuimini leaves by HPLC-ESIMS/MS analysis was carried out., Results: Our results indicate that all fractions, for exception Hex, present noteworthy antioxidant activity, mainly in EtOAc and ButOH fractions (FRAP 1154.49 ± 67.37 and 1178.27 ± 21.26 μmol trolox eq g -1 , respectively; ORAC 1224.63 ± 58.16 and 1313.53 ± 85.23 μmol trolox eq g -1 , respectively; DPPH IC 50 15.7 ± 2.4 and 23.5 ± 2.7 μg mL -1 , respectively). Regarding the antiglycant activity (BSA/fructose and Arginine/Methylglyoxal models), all fraction, for exception Hex, presented inhibition higher than 85%. All fractions were capable to inhibit 100% of α-amylase and the fractions DCM, EtOAc and ButOH inhibited α-glucosidase more than 50%. Regarding the lipase assay, DCM and Hex had the best activity (31.5 ± 14.3 and 44.3 ± 4.5 μg mL -1 , respectively). Various biomolecules known as potent antioxidants were identified in these fractions, such as quercetin, kaempferol, luteolin and (Epi)catechin., Conclusion: S. cumini fractions and quercetin presented promising antioxidant and antiglycation properties as well as the ability to inhibit digestive enzymes. This study presents new biological activities not yet described for S. cumini which provide new possibilities for further studies in order to assess the antidiabetic potential of S. cumini fractions especially EtOAc and ButOH., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Different parts of Annona crassiflora Mart., a native species from Brazilian savanna, were traditionally used for the treatment of a wide variety of ailments including arthritis. Thus, this study aimed to investigate the possible antinociceptive and anti-inflammatory properties of a polyphenol-enriched fraction of the fruit peel of A. crassiflora, named here as EtOAc, in mice. Pro-inflammatory cytokines and nitric oxide (NO) production were evaluated in LPS-activated macrophages. Then, EtOAc fraction was administered by oral route in male C57BL/6/J mice, and the animals were submitted to glutamate-induced nociception and complete Freund's adjuvant (CFA)-induced monoarthritis tests to assess nociception (mechanical, spontaneous and cold pain) and inflammation (edema and neutrophil infiltration), and to the open-field and rotarod tests for motor performance analysis. EtOAc fraction inhibited the production of IL-6 and NO in the LPS-induced macrophages, and reduced spontaneous nociception induced by glutamate, without altering the animals' locomotor activity. In addition, the polyphenol-enriched fraction was able to revert the early and late hyperalgesia induced by CFA, as well as edema at the acute phase. Reduction of myeloperoxidase activity and inflammatory cell infiltration was observed in the paw tissue of mice injected with CFA and treated with EtOAc fraction. Together, our results support the antinociceptive and anti-inflammatory effects of the polyphenol-enriched fraction of A. crassiflora fruit peel and suggest that these effects are triggered, at least in part, by suppressing pro-inflammatory cytokines and neutrophils infiltration.

Monitoring of blood glucose is an invasive, painful and costly practice in diabetes. Consequently, the search for a more cost-effective (reagent-free), non-invasive and specific diabetes monitoring method is of great interest. Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy has been used in diagnosis of several diseases, however, applications in the monitoring of diabetic treatment are just beginning to emerge. Here, we used ATR-FTIR spectroscopy to evaluate saliva of non-diabetic (ND), diabetic (D) and insulin-treated diabetic (D+I) rats to identify potential salivary biomarkers related to glucose monitoring. The spectrum of saliva of ND, D and D+I rats displayed several unique vibrational modes and from these, two vibrational modes were pre-validated as potential diagnostic biomarkers by ROC curve analysis with significant correlation with glycemia. Compared to the ND and D+I rats, classification of D rats was achieved with a sensitivity of 100%, and an average specificity of 93.33% and 100% using bands 1452 cm-1 and 836 cm-1, respectively. Moreover, 1452 cm-1 and 836 cm-1 spectral bands proved to be robust spectral biomarkers and highly correlated with glycemia (R2 of 0.801 and 0.788, P < 0.01, respectively). Both PCA-LDA and HCA classifications achieved an accuracy of 95.2%. Spectral salivary biomarkers discovered using univariate and multivariate analysis may provide a novel robust alternative for diabetes monitoring using a non-invasive and green technology., Competing Interests: No competing interests.

Pain relief represents a critical unresolved medical need. Consequently, the search for new analgesic agents is intensively studied. Annona crassiflora, a native species of the Brazilian Savanna, represents a potential source for painful treatment. This study aimed to investigate the antinociceptive potential of A. crassiflora fruit peel, focusing on its major alkaloid, stephalagine, in animal models of pain evoked by the activation of transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) channels. Male C57BL/6/J mice were submitted to formalin-, cinnamaldehyde-, and capsaicin-induced nociception tests to assess nociceptive behavior, and to the open-field and rotarod tests for motor performance analyses. Moreover, the stephalagine's effect was tested on capsaicin- and cinnamaldehyde-induced Ca 2+ influx in spinal cord synaptosomes. In silico assessments of the absorption, distribution, metabolism and central nervous system permeability of stephalagine were carried out. The ethanol extract and alkaloidal fraction reduced the nociception induced by formalin. When administered by oral route (1 mg/kg), stephalagine reduced the spontaneous nociception and paw edema induced by TRPV1 agonist, capsaicin, and by TRPA1 agonists, cinnamaldehyde- and formalin, without altering the animals' locomotor activity. The prediction of in silico pharmacokinetic properties of stephalagine suggests its capacity to cross the blood-brain barrier. Furthermore, this alkaloid reduces the capsaicin- and cinnamaldehyde-mediated Ca 2+ influx, indicating a possible modulation of TRPV1 and TRPA1 channels, respectively. Together, our results support the antinociceptive and anti-edematogenic effects of the A. crassiflora fruit peel and suggest that these effects are triggered, at least in part, by TRPV1 and TRPA1 modulation by stephalagine., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Bauhinia forficata Link., a cerrado native plant, is used as a complementary treatment for Type 2 Diabetes Mellitus (T2DM). Several studies involving this plant have shown that it has prominent potential to combat hyperglycemia and oxidative stress. Our objective was suggest the phytochemical constitution of fractions of ethanol extract of B. forficata leaves using HPLC-ESI-MS/MS, and evaluates their activities in enzymatic assays to evaluate their inhibitory potential against α-amylase, α-glucosidase and lipase, as well as their antioxidant and anti-glycation capacities. In addition, we evaluated the cytotoxic effects of these fractions using rodents macrophages and erythrocytes. The ETOAC e ButOH fractions showed high polyphenols concentrations, having been determined 11 flavonoids, including the kaempferitrin, the phytomarker of B. forficata Link. In addition, all fractions presented higher antioxidant and antiglycation activities and prominent capacities to digestive enzymes inhibition. On the other hand, in the cellular assays, none fractions showed cytotoxic and hemolytic effects, able to combat the ROS production in macrophages. Thus, this study presented new results on the biological activities of this plant, contributing to the understanding of the action and effectiveness of its use in the management of diabetes mellitus and its complications., Competing Interests: Declaration of Competing Interest The authors have declared that there is no conflict of interest., (Copyright © 2019. Published by Elsevier Masson SAS.)

This study tested the effect of isoflavone supplementation in addition to combined exercise training in salivary oxidative stress markers in non-obese postmenopausal women. Thirty-two postmenopausal women without hormone therapy were randomly assigned to exercise + placebo ( n  = 15) or exercise + isoflavone supplementation ( n  = 17) groups. They performed 30 sessions of combined exercises (aerobic plus resistance) over ten weeks and consumed 100 mg of isoflavone supplementation or placebo. Saliva samples were collected after an overnight fast. Superoxide dismutase, total antioxidant capacity, thiobarbituric acid reactive substances, catalase, total protein and nitrite were determined before and after ten weeks of the intervention. The ANOVA two-way analysis of variance was applied with α of 5%. Both groups increase ( p <0.05) superoxide dismutase activity and decrease catalase levels. There was interaction (time × group) in both nitrite and thiobarbituric acid reactive substances results, with increase ( p <0.05) in placebo group and decrease ( p <0.05) in isoflavone group. No difference was found for total antioxidant capacity or total protein. The combination of isoflavone supplementation and exercise training can promote an antioxidant effect through reduction of lipid peroxidation and concentrations of salivary nitrite., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2020 JCBN.)

Advanced glycation end-products (AGEs) have been reported as results of increased oxidative stress. Consequently, the search for new antioxidant and anti-glycating agents is under intense investigation. Plant-derived procyanidins have previously demonstrated anti-glycation properties. Thus, this study aimed to isolate procyanidins from Annona crassiflora fruit peel, a species from the Brazilian Savanna, and investigate their antioxidant and anti-glycation effects. Free radical scavenging and quenching properties, formation of reactive oxygen species (ROS), AGEs, protein carbonyl and thiol groups, lipid peroxidation, crosslinked AGEs, as well as glycated catalase activity, were analyzed. In addition, in silico assessment of absorption, distribution, metabolism, excretion and toxicity was carried out. The procyanidins-enriched fraction, named here as F7, showed high antioxidant and anti-glycation capacities, with inhibitory activities against lipid peroxidation, and AGEs and ROS formation. In addition, there were reductions in AGEs-induced crosslinks and protein carbonyls and protective effects against oxidation of thiol groups and glycated-catalase. ADMET predictions of F7 showed favorable absorption and distribution, with no hepatotoxicity or mutagenicity. Together, our results support the anti-glycation activities of the procyanidins-enriched fraction from A. crassiflora, and suggest that these effects are triggered, at least in part, by scavenging free radical and dicarbonyls intermediates.

The increase in antioxidant responses promoted by regular physical activity is strongly associated with the attenuation of chronic oxidative stress and physiological mechanisms related to exercise adaptation. The aim of this work was to evaluate and compare how different exercise protocols (HIIE: high-intensity interval exercise, CE: continuous exercise, and RE: resistance exercise) may alter salivary and plasmatic antioxidants and salivary markers of exercise intensity and nitric oxide. Thirteen healthy, trained male subjects were submitted to the three exercise protocols. Blood and saliva samples were collected at the points preexercise, postexercise, and 3 hours postexercise. Antioxidants (total antioxidant capacity, superoxide dismutase and catalase activities, and levels of reduced glutathione and uric acid), markers of exercise intensity (salivary total protein and amylase activity), and salivary nitric oxide were evaluated. As a result, all exercise protocols increased the markers of exercise intensity and nitric oxide. Antioxidant response was increased after exercise, and it was found that a single HIIE session exerts a similar pattern of antioxidant response compared to CE, in plasma and saliva samples, while RE presented minor alterations. We suggest that HIIE may lead to alterations in antioxidants and consequently to the physiological processes related to redox, similar to the CE, with the advantage of being performed in a shorter time. In addition, the antioxidant profile of saliva samples showed to be very similar to that of plasma, suggesting that saliva may be an alternative and noninvasive tool in sports medicine for the study of antioxidants in different physical exercise protocols., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2019 Adriele V. Souza et al.)

Scientific research based on medicinal plants has been highlighted as a complementary treatment to T2DM, stand out the Vochysiaceae family, which have been widely used in folk medicine by traditional South American communities to treat some diseases. Our study aimed to investigate the antioxidant and antiglycation activities of ethanol extracts of leaves (LF) and stem barks (SB) of Vochysiaceae species, evaluated their capacities to inhibit glycoside and lipid hydrolases related to T2DM and molecular identification by HPLC-ESI-MS/MS. Our main findings indicate that the ethanolic extract of four of eight analyzed plants such as LF and SB of Q. grandiflora, Q. parviflora, V. elliptica and Calisthene major exhibited, respectively, potential of α-amylase inhibition (IC 50 of LF: 5.7 ± 0.6, 4.1 ± 0.5, 5.8 ± 0.5, 3.2 ± 0.6 and IC 50 of SB: 3.3 ± 0.7, 6.2 ± 2.0, 121.0 ± 8.6 and 11.2 ± 2.8 μg/mL), capacities of antioxidant (ORAC of LF: 516.2 ± 0.1, 547.6 ± 4.9, 544.3 ± 6.1, 442.6 ± 2.4 and ORAC of SB: 593.6 ± 22.3, 497.7 ± 0.8, 578 ± 12.3, 593.6 ± 19.5 µmol trolox eq/g; FRAP of LF: 796.1 ± 0.9, 427.7 ± 22.0, 81.0 ± 1.9, 685 ± 37.9 and FRAP of SB: 947.4 ± 24.9, 738.6 ± 24.3, 98.8 ± 7.9, 970.8 ± 13.9 µmol trolox eq/g; DPPH IC 50 of LF: 14.2 ± 1.8, 36.3 ± 6.9, 11.8 ± 1.9, 13.3 ± 1.2 and DPPH IC 50 of SB: 16.0 ± 3.0, 15.5 ± 1.9, 126.1 ± 23. 6, 5.3 ± 0.3 μg/mL, respectively) and antiglycation (BSA/Frutose IC 50 of LF: 43.1 ± 3.4, 52.1 ± 6.0, 175.5 ± 32, 8, 111.8 ± 14.7 and BSA/Frutose IC 50 of SB:, 40.1 ± 11.9, 51.2 ± 16. 7, 46.6 ± 5.7, 53.5 ± 13.6 μg/mL) and presence of polyphenols, such as flavonoids and condensed tannins. The extracts presented low ability to inhibit α-glycosidase and lipase enzymes in the initial assays, with values below 40% of inhibition. In BSA/methylglyoxal, only Q. grandiflora SB, V. eliptica LF and V. tucanorum LF showed activity (IC 50 : 655.5 ± 208.5, 401.9 ± 135.2 and 617.1 ± 80.6 μg/mL, respectively) and only C. major LF and SB, in Arg/methylglyoxal (IC 50 : 485.1 ± 130.8 and 468.0 ± 150.5 μg/ml, respectively). This study presented new findings about the biological and pharmacological potential of some species of Vochysiaceae family, contributing to the understanding of the action and efficacy in use of these plants, in their management of postprandial hyperglycemia and in glycation and oxidative processes that contribute to managing diabetes mellitus., (Copyright © 2019 Elsevier Inc. All rights reserved.)