Phytochemical composition of aerial parts and roots of Pfaffia glomerata (Spreng.) Pedersen and anticholinesterase, antioxidant, and antiglycation activities.

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.

Biochemical characterization and assessment of leishmanicidal effects of a new L-amino acid oxidase from Crotalus durissus collilineatus snake venom (CollinLA AO-I).

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 IC50 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.

What do we know about Toll-Like Receptors Involvement in Gout Arthritis?

Toll-like receptors (TLRs) are a well-characterized family of cell-bound pattern recognition receptors able to identify and respond to conserved structures of external microorganisms or Pathogen Molecular-Associated Pattern (PAMPs). They can also interact with Damage-Associated Molecular Patterns (DAMPs) involved with any infectious and sterile cell stress of tissue injury. Accumulated knowledge about TLRs has revealed that these receptors and intracellular signaling pathways triggered through TLR activation contribute to the physiopathology of different inflammatory diseases, including arthritic conditions. Mostly, the literature focuses on exploring TLRs in rheumatoid and osteoarthritis. However, TLRs also seem to be an essential mediator for monosodium urate (MSU) crystals-induced gouty arthritis, both in animal models and humans. Accordingly, naked MSU crystals have a highly negatively charged surface recognized by TLRs; intracellular adapter protein MyD88 are significant mediators of MSU crystals-induced IL1ß production in mice, and gouty patients demonstrate a robust positive correlation between TLR4 mRNA level and serum IL1ß. Here, we revised the literature evidence regarding the involvement of TLRs in gout arthritis pathogenesis, with particular reference to TLR2 and TLR4, by analyzing the actual literature data.

Polyphenols-Rich Fraction from Annona muricata Linn. Leaves Attenuates Oxidative and Inflammatory Responses in Neutrophils, Macrophages, and Experimental Lung Injury.

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.

CdSe magic-sized quantum dots attenuate reactive oxygen species generated by neutrophils and macrophages with implications in experimental arthritis.

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.

Flavonoids and proanthocyanidins-rich fractions from Eugenia dysenterica fruits and leaves inhibit the formation of advanced glycation end-products and the activities of α-amylase and α-glucosidase.

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 (CH2Cl2F) and EtOAcF from leaf had high antioxidant capacities (ORAC >5500 µmol trolox eq g-1, FRAP >1500 µmol trolox eq g-1 and DPPH IC50 < 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 (CH2Cl2 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.

Increased selenium concentration in the synthesis of CdSe magic-sized quantum dots affects how the brain responds to oxidative stress.

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 Cd2+ 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 Cd2+ -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 Cd2+ ) 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 Cd2+ ions on the surface of quantum dots, changing toxicity, and aiming interesting strategies of nanomaterials in biological systems.

Citrullinated human fibrinogen triggers arthritis through an inflammatory response mediated by IL-23/IL-17 immune axis.

Rheumatoid arthritis (RA) is an autoimmune disease that causes joint destruction. Although its etiology remains unknown, citrullinated proteins have been considered as an auto-antigen able to trigger an inflammatory response in RA. Herein, we modified the classical antigen-induced arthritis (AIA) model by using citrullinated human plasma fibrinogen (hFIB) as an immunogen to investigate the mechanism of inflammation-driven joint damage by citrullinated hFIB in C57BL/6 mice. We found that hFIB-immunized mice showed high serum levels of anti-citrullinated peptides antibodies (ACPAs). Moreover, hFIB immunized mice showed increased mechanical hyperalgesia, massive leukocyte infiltration, high levels of inflammatory mediators, and progressive joint damage after the intra-articular challenge with citrullinated hFIB. Interestingly, hFIB-induced arthritis was dependent on IL-23/IL-17 immune axis-mediated inflammatory responses since leukocyte infiltration and mechanical hyperalgesia were abrogated in Il17ra-/- and Il23a-/- mice. Thus, we have characterized a novel model of experimental arthritis suitable to investigate the contribution of ACPAs and Th17 cell-mediated immune response in the pathogenesis of RA.

Antioxidant compounds of Kielmeyera coriacea Mart. with α-amylase, lipase and advanced glycation end-product inhibitory activities.

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/MSn 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 IC50<4 µg/mL), and inhibited ROS production (p < 0.01), lipid peroxidation (p < 0.001), glycation (IC50 ~ 10 µg/mL in the BSA-fructose assay; IC50 ~ 200 µg/mL in the BSA-methylglyoxal and arginine-methylglyoxal assays), α-amylase (IC50<0.1 µg/mL) and lipase (IC50<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.

Antioxidant compounds from Annona crassiflora fruit peel reduce lipid levels and oxidative damage and maintain the glutathione defense in hepatic tissue of Triton WR-1339-induced hyperlipidemic mice.

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.

A 20-hydroxyecdysone-enriched fraction from Pfaffia glomerata (Spreng.) pedersen roots alleviates stress, anxiety, and depression in mice.

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).

Anacardium humile St. Hil as a novel source of antioxidant, antiglycation and α-amylase inhibitors molecules with potential for management of oxidative stress and diabetes.

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 IC50 µg/mL IC50 DPPH) and EtOAc (1300.11 ± 33.04 ORAC, 236.21 ± 23.86 FRAP and 3.03 ± 0.14 µg/mL IC50 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 IC50 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 IC50 values, especially DCM, EtOAc, ButOH and H2O (IC50 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.

Antidiabetic effects of Syzygium cumini leaves: A non-hemolytic plant with potential against process of oxidation, glycation, inflammation and digestive enzymes catalysis.

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/H2O) 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 IC50 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.

Stephalagine, an aporphine alkaloid from Annona crassiflora fruit peel, induces antinociceptive effects by TRPA1 and TRPV1 channels modulation in mice.

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 Ca2+ 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 Ca2+ 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.

Protective effects of a polyphenol-enriched fraction of the fruit peel of Annona crassiflora Mart. on acute and persistent inflammatory pain.

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.

Antidiabetic potential of Bauhinia forficata Link leaves: a non-cytotoxic source of lipase and glycoside hydrolases inhibitors and molecules with antioxidant and antiglycation properties.

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.