RESUMO

Metabolic alterations are increasingly recognized as important aspects of colorectal cancer (CRC), offering potential avenues for identifying therapeutic targets. Previous studies have demonstrated the cytotoxic potential of bamboo leaf extract obtained from Guadua incana (BLEGI) against HCT-116 colon cancer cells. However, the altered metabolic pathways in these tumor cells remain unknown. Therefore, this study aimed to employ an untargeted metabolomic approach to reveal the metabolic alterations of the endometabolome and exometabolome of HCT-116 cells upon exposure to BLEGI treatment. First, a chemical characterization of the BLEGI was conducted through liquid chromatography coupled with mass spectrometry (LC-MS). Next, we assessed cell viability via MTT and morphological analysis using an immunofluorescence assay against colon cancer cells, and anti-inflammatory activity using an LPS-stimulated macrophage model. Subsequently, we employed LC-MS and proton nuclear magnetic resonance (1H-NMR) to investigate intra- and extracellular changes. Chemical characterization primarily revealed the presence of compounds with a flavone glycoside scaffold. Immunofluorescence analysis showed condensed chromatin and subsequent formation of apoptotic bodies, suggesting cell death by apoptosis. The results of the metabolomic analysis showed 98 differential metabolites, involved in glutathione, tricarboxylic acid cycle, and lipoic acid metabolism, among others. Additionally, BLEGI demonstrated significant nitric oxide (NO) inhibitory capacity in macrophage cells. This study enhances our understanding of BLEGI's possible mechanism of action and provides fresh insights into therapeutic targets for treating this disease.

Assuntos

Neoplasias do Colo , Extratos Vegetais , Folhas de Planta , Humanos , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Folhas de Planta/química , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Células HCT116 , Metabolômica/métodos , Metaboloma/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Animais , Células RAW 264.7 , Camundongos , Cromatografia Líquida

RESUMO

INTRODUCTION: Furoxan and benzofuroxan are compounds containing an N-oxide function, known for their diverse pharmacological properties, including antimicrobial and antiinflammatory effects. This study aimed to investigate these activities using an in-house library of N-oxide compounds. METHOD: Twenty compounds were tested against both Gram-positive and Gram-negative bacteria, including Cutibacterium acnes (C. acnes), a microorganism implicated in the development of acne vulgaris. One compound, (E)-4-(3-((2-(3-hydroxybenzoyl)hydrazone)methyl)phenoxy)-3- (phenylsulfonyl)-1,2,5-oxadiazol-2-N-oxide (compound 15), exhibited selective antimicrobial activity against C. acnes, with a Minimum Inhibitory Concentration (MIC) value of 2 µg/mL. Indirect measurement of Nitric Oxide (NO) release showed that compound 15 and isosorbide dinitrate, when treated with L-cysteine, produced nitrite levels of 20.1% and 9.95%, respectively. Using a NO scavenger (PTIO) in combination with compound 15 in a culture of C. acnes resulted in reduced antimicrobial activity, indicating that NO release is part of its mechanism of action. Cytotoxicity assessments using murine macrophages showed cellular viability above 70% at concentrations up to 0.78 µg/mL. RESULTS: Measurements of Interleukin-1 beta (IL1-ß) and Tumor Necrosis Factor-alpha (TNF-α) indicated that compound 15 did not reduce the levels of these pro-inflammatory cytokines. Sustained NO production by inducible Nitric Oxide Synthase (iNOS) in macrophages or neutrophils has been found to be involved in the inflammatory process in acne vulgaris and lead to toxicity in surrounding tissues. Nitrite levels in the supernatant of murine macrophages were found to be decreased at a concentration of 0.78 µg/mL of compound 15, indicating an anti-inflammatory effect. In vivo studies were conducted using Balb/c nude mice inoculated subcutaneously with C. acnes. Cream and gel formulations of compound 15 were applied to treat the animals, along with commercially available anti-acne drugs, for 14 days. Animals treated with a cream base containing 5% of compound 15 exhibited less acanthosis with mild inflammatory infiltration compared to other groups, highlighting its anti-inflammatory properties. CONCLUSION: Similar results were observed in the benzoyl peroxide group, demonstrating that compound 15 presented comparable anti-inflammatory activity to the FDA-approved drug. These promising results suggest that compound 15 has a dual mechanism of action, with selective antimicrobial activity against C. acnes and notable anti-inflammatory properties, making it a potential prototype for developing new treatments for acne vulgaris.

RESUMO

Neurological commitment is a neglected manifestation of Chagas disease (CD). Meningoencephalitis mainly affects children and immunosuppressed patients, while stroke can occur with or without cardiac compromise. One of the possible causes of stroke development is microvascular commitment. Our group previously described that experimental Trypanossoma cruzi acute infection leads to cerebral microvasculopathy. This condition is characterized by decreased capillary density, increased leukocyte rolling and adhesion, and endothelial dysfunction. CD was discovered 114 years ago, and until today, only two drugs have been available for clinical treatment: benznidazole and nifurtimox. Both present a high cure rate for the acute phase (80%) and small cure rate for the chronic phase (20%). In addition, the high occurrence of side-effects, without proper medical follow-up, can result in treatment abandonment. Therefore, the search for new therapeutic schemes is necessary. Statins are drugs already used in the clinic that have several pleiotropic effects including endothelial function improvement, anti-inflammatory action, as well as trypanocidal effects, making them a potential alternative treatment for brain microvasculopathy in CD. Here, we investigate the effect of lovastatin (LOV) on brain microvasculopathy and inflammatory parameters. Swiss Webster mice were intraperitoneally inoculated with the Y strain of T. cruzi. Treatment with lovastatin (20 mg/kg/day) was initiated 24 h after the infection and continued for 14 consecutive days. We observed that LOV treatment did not affect parasitemia, brain microcirculation alterations, or the reduction in cerebral blood flow caused by T. cruzi infection. Also, LOV did not prevent the increased number of CD3+ cells and eNOS levels in the T. cruzi-infected brain. No alterations were observed on VCAM-1 and MCP-1 expressions, neither caused by infection nor LOV treatment. However, LOV prevented the increase in F4/80+ cells and ICAM-1 levels in the brain caused by acute infection with T. cruzi. These results suggest an anti-inflammatory activity of LOV, but more studies are needed to elucidate the role of LOV in CD acute infection.

RESUMO

Chagas disease, caused by the protozoan Trypanosoma cruzi, affects 6-7 million people worldwide. The dichloromethane extract obtained from the aerial parts of Gymnocoronis spilanthoides var subcordata showed trypanocidal activity in vitro. The fractionation of the dewaxed organic extract via column chromatography led to the isolation of three diterpenoids: ent-9α,11α-dihydroxy-15-oxo-kaur-16-en-19-oic acid or adenostemmoic acid B, (16R)-ent-11α-hydroxy-15-oxokauran-19-oic acid and ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic acid. These compounds showed IC50 values of 10.6, 15.9 and 4.8 µM against T. cruzi epimastigotes, respectively. When tested against amastigotes, the diterpenoids afforded IC50 values of 6.1, 19.5 and 60.6 µM, respectively. The cytotoxicity of the compounds was tested on mammalian cells using an MTT assay, resulting in CC50s of 321.8, 23.3 and 14.8 µM, respectively. The effect of adenostemmoic acid B on T. cruzi was examined at the ultrastructural level using transmission microscopy. Treatment with 20 µM for 48 h stimulated the formation of abnormal cytosolic membranous structures in the parasite. This compound also showed an anti-inflammatory effect in murine macrophages stimulated with LPS and other TLR agonists. Treatment of macrophages with adenostemmoic acid B was able to reduce TNF secretion and nitric oxide production, while increasing IL-10 production. The combination of adenostemmoic acid B with benznidazole resulted in greater inhibition of NF-kB and a decrease in nitrite concentration. The administration of adenostemmoic acid B to mice infected with trypomastigotes of T. cruzi at the dose of 1 mg/kg/day for five days produced a significant decrease in parasitemia levels and weight loss. Treatment with the association with benznidazole increased the survival time of the animals. In view of these results, adenostemmoic acid B could be considered a promising candidate for further studies in the search for new treatments for Chagas disease.

RESUMO

Steatosis is characterized by fat accumulation and insulin resistance (IR) in hepatocytes, which triggers a pro-oxidant, pro-inflammatory environment that may eventually lead to cirrhosis or liver carcinoma. This work was aimed to assess the effect of Sechium edule root hydroalcoholic extract (rSe-HA) (rich in cinnamic and coumaric acid, among other phenolic compounds) on triglyceride esterification, lipid degradation, AMPK expression, and the phosphorylation of insulin receptor in a Ser312 residue, as well as on the redox status, malondialdehyde (MDA) production, and the production of proinflammatory cytokines in an in vitro model of steatosis induced by oleic acid, to help develop a phytomedicine that could reverse this pathology. rSe-HA reduced triglyceride levels in hepatocyte lysates, increased lipolysis by activating AMPK at Thr172, and improved the redox status, as evidenced by the concentration of glycerol and formazan, respectively. It also prevented insulin resistance (IR), as measured by glucose consumption and the phosphorylation of the insulin receptor at Ser312. It also prevented TNFα and IL6 production and decreased the levels of MDA and nitric oxide (ON). Our results indicate that rSe-HA reversed steatosis and controlled the proinflammatory and prooxidant environment in oleic acid-induced dysfunctional HepG2 hepatocytes, supporting its potential use to control this disorder.

RESUMO

Diketopiperazine alkaloids have proven the most abundant heterocyclic alkaloids up to now, which usually process diverse scaffolds and rich biological activities. In our search for bioactive diketopiperazine alkaloids from marine-derived fungi, two novel diketopiperazine alkaloids, penipiperazine A (1) and its biogenetically related new metabolite (2), together with a known analogue neofipiperzine C (3), were obtained from the strain Penicillium brasilianum. Their planar structures and absolute configurations were elucidated by extensive spectroscopic analyses, 13C NMR calculation, Marfey's, ECD, and ORD methods. Compound 1 featured a unique 6/5/6/6/5 indole-pyrazino-pyrazino-pyrrolo system, and its plausible biogenetic pathway was also proposed. Additionally, compounds 1-3 have been tested for their inflammatory activities. 1 and 2 significantly inhibited the release of NO and the expression of related pro-inflammatory cytokines on LPS-stimulated RAW264.7 cells, suggesting they could be attracting candidate for further development as anti-inflammatory agent. KEY POINTS: • A novel diketopiperazine alkaloid featuring a unique 6/5/6/6/5 indole-pyrazino-pyrazino-pyrrolo system was isolated from the marine fungus Penicillium brasilianum. • The structure of 1 was elucidated by detailed analysis of 2D NMR data, 13C NMR calculation, Marfey's, ECD, and ORD methods. • Compounds 1 and 2 significantly inhibited the release of NO and the expression of related pro-inflammatory cytokines on LPS-stimulated RAW264.7 cells.

Assuntos

Alcaloides , Penicillium , Dicetopiperazinas/farmacologia , Lipopolissacarídeos , Fungos , Alcaloides/química , Indóis , Anti-Inflamatórios/farmacologia , Citocinas , Estrutura Molecular , Alcaloides Indólicos/farmacologia , Alcaloides Indólicos/química

RESUMO

Silk fibroin is a fibrillar protein obtained from arthropods such as mulberry and non-mulberry silkworms. Silk fibroin has been used as a dressing in wound treatment for its physical, chemical, mechanical, and biological properties. This systematic review analyzed studies from PubMed, Web of Science, and Scopus databases to identify the molecules preferred for functionalizing silk fibroin-based dressings and to describe their mechanisms of exhibiting anti-inflammatory and antibacterial properties. The analysis of the selected articles allowed us to classify the dressings into different conformations, such as membranes, films, hydrogels, sponges, and bioadhesives. The incorporation of various molecules, including antibiotics, natural products, peptides, nanocomposites, nanoparticles, secondary metabolites, growth factors, and cytokines, has allowed the development of dressings that promote wound healing with antibacterial and immunomodulatory properties. In addition, silk fibroin-based dressings have been established to have the potential to regenerate wounds such as venous ulcers, arterial ulcers, diabetic foot, third-degree burns, and neoplastic ulcers. Evaluation of the efficacy of silk fibroin-based dressings in tissue engineering is an area of great activity that has shown significant advances in recent years.

Assuntos

Antibacterianos , Anti-Inflamatórios , Bandagens , Fibroínas , Cicatrização , Fibroínas/química , Antibacterianos/química , Antibacterianos/farmacologia , Humanos , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Animais , Cicatrização/efeitos dos fármacos

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Mimosa caesalpiniifolia (Sansão-do-Campo) is a native species of the caatinga in northeastern Brazil that has been studied for its potential anti-inflammatory and antidepressant activity. It is popularly consumed as a medicinal plant and its pharmacological benefits are evidenced in the literature. AIM OF THE STUDY: The present work was carried out to promote the chemical profile and evaluate the pharmacological activity of the dry extract and the ethyl acetate fraction obtained from the dry leaves of Mimosa caesalpiniifolia. MATERIALS AND METHODS: The leaves were collected in the municipality of Alfenas-MG and subjected to drying, followed by division in a knife mill. The preparation of the dry extract was carried out by the extraction method using simple percolation and the fraction was obtained by liquid-liquid partition. Part of the extractive solution was concentrated in a rotary evaporator followed by a drying process using the spray technique with the addition of colloidal silicon dioxide. The dry extract (33.33%) showed a higher yield in mass when compared to the yield of the ethyl acetate fraction (19.67%). The in vivo pharmacological evaluation was conducted with a total of 82 male Wistar rats that underwent cecal ligation and perforation surgery to induce the inflammatory process. One week after surgery, these animals were treated for 7 days with the dry extract and the ethyl acetate fraction and submitted to behavioral tests (open field and forced swimming). RESULTS: The chemical results were obtained through analysis by HPLC-PDA coupled to a mass spectrometer, enabling the verification of the presence of phenolic acids, flavonoids, aglycones, and glycosides, in addition to tannins. This corroborates with data present in the literature for the genus Mimosa sp. Some compounds had their structure determined, where they were identified as catechin (m/z 288.97), cassiaocidentalin A (m/z 560.75), and procyanidin B2 [(epi)catechin-(epi)catechin; m/z 576.83)]. It was found that the animals that were submitted to the treatment did not present statistically significant results, demonstrating that the pharmacological action evaluated in the test was not highlighted in this type of experiment. The groups that underwent treatment had an aggravated locomotor activity. CONCLUSIONS: The results found with the chemical study contributed to the knowledge of the plant species studied. On the other hand, further studies are needed to provide a better understanding of the pharmacological evaluation of Mimosa caesalpiniifolia.

Assuntos

Acetatos , Catequina , Mimosa , Ratos , Animais , Ratos Wistar , Mimosa/química , Extratos Vegetais/farmacologia , Extratos Vegetais/análise , Folhas de Planta/química

RESUMO

Tetrahydrocurcumin, the most abundant curcumin transformation product in biological systems, can potentially be a new alternative therapeutic agent with improved anti-inflammatory activity and higher bioavailability than curcumin. In this article, we describe the synthesis and evaluation of the anti-inflammatory activities of tetrahydrocurcumin derivatives. Eleven tetrahydrocurcumin derivatives were synthesized via Steglich esterification on both sides of the phenolic rings of tetrahydrocurcumin with the aim of improving the anti-inflammatory activity of this compound. We showed that tetrahydrocurcumin (2) inhibited TNF-α and IL-6 production but not PGE2 production. Three tetrahydrocurcumin derivatives inhibited TNF-α production, five inhibited IL-6 production, and three inhibited PGE2 production. The structure-activity relationship analysis suggested that two factors could contribute to the biological activities of these compounds: the presence or absence of planarity and their structural differences. Among the tetrahydrocurcumin derivatives, cyclic compound 13 was the most active in terms of TNF-α production, showing even better activity than tetrahydrocurcumin. Acyclic compound 11 was the most effective in terms of IL-6 production and retained the same effect as tetrahydrocurcumin. Moreover, acyclic compound 12 was the most active in terms of PGE2 production, displaying better inhibition than tetrahydrocurcumin. A 3D-QSAR analysis suggested that the anti-inflammatory activities of tetrahydrocurcumin derivatives could be increased by adding bulky groups at the ends of compounds 2, 11, and 12.

Assuntos

Curcumina , Curcumina/química , Fator de Necrose Tumoral alfa , Interleucina-6 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Relação Estrutura-Atividade

RESUMO

Medicines for chronic inflammation can cause gastric ulcers and hepatic and renal issues. An alternative treatment for chronic inflammation is that of natural bioactive compounds, which present low side effects. Extracts of Jatropha cordata (Ortega) Müll. Arg. have been evaluated for their cytotoxicity and anti-inflammatory activity; however, testing pure compounds would be of greater interest. Campesteryl palmitate, n-heptyl ferulate, palmitic acid, and a mixture of sterols, i.e., brassicasterol, campesterol, ß-sitosterol, and stigmasterol, were obtained from an ethyl acetate extract from J. cordata (Ortega) Müll. Arg. bark using column chromatography. The toxicity and in vitro anti-inflammatory activities were evaluated using RAW 264.7 murine macrophage cells. None of the products assessed exhibited toxicity. The sterol mixture exhibited greater anti-inflammatory activity than the positive control, and nitric oxide (NO) inhibition percentages were 37.97% and 41.68% at 22.5 µg/mL and 30 µg/mL, respectively. In addition, n-heptyl ferulate decreased NO by 30.61% at 30 µg/mL, while campesteryl palmitate did not show anti-inflammatory activity greater than the positive control. The mixture and n-heptyl ferulate showed NO inhibition; hence, we may conclude that these compounds have anti-inflammatory potential. Additionally, further research and clinical trials are needed to fully explore the therapeutic potential of these bioactive compounds and their efficacy in treating chronic inflammation.

RESUMO

Many species from Myrtaceae have traditionally been used in traditional medicine as anti-inflammatory, antimicrobial, antidiarrheal, antioxidant and antirheumatic, besides in blood cholesterol reduction. In the present work, the anti-inflammatory activity of essential oils from eighteen Myrtaceae spp. were evaluated according to their ex-vivo anti-inflammatory activity in human blood, and the corresponding biomarkers were determined using untargeted metabolomics data and multivariate data analysis. From these studied species, six displayed anti-inflammatory activity with percentage rates of inhibition of PGE2 release above 70%. Caryophyllene oxide (1), humulene epoxide II (2), ß-selinene (3), α-amorphene (4), α-selinene (5), germacrene A (6), ß-bisabolene (7), α-muurolene (8), α-humulene (9), ß-gurjunene (10), myrcene (11), ß-elemene (12), α-cadinol (13), α-copaene (14), E-nerolidol (15) and ledol (16) were annotated as potential anti-inflammatory biomarkers. The results obtained in this study point to essential oils from species of the Myrtaceae family as a rich source of anti-inflammatory agents.

RESUMO

It has been reported that pineapple (Ananas comosus) contains healthy nutrients and phytochemicals associated with antioxidant and anti-inflammatory capacities. However, a substantial amount of pineapple residue is produced due to a lack of valorization applications at the industrial scale, resulting in the loss of valuable nutrients. Solid-state fermentation (SSF) is proposed as an innovative strategy to enhance the release of bound phenolics from pineapple residues. In this work, the effects of SSF of pineapple peels with Lactobacillus plantarum, Lactobacillus rhamnosus, and Aspergillus oryzae on the release of phenolic compounds and their antioxidant and anti-inflammatory activities were evaluated, respectively. Pineapple peel extracts after SSF showed an increase in the release of phenolic compounds (248.11% with L. plantarum, 182% with A. oryzae, and 180.10% with L. rhamnosus), which led to an increase in the cellular antioxidant (81.94% with L. rhamnosus) and anti-inflammatory potential (nitric oxide inhibition of 62% with L. rhamnosus) compared to non-fermented extracts. Therefore, SSF of pineapple peels with L. plantarum, L. rhamnosus, and A. oryzae thrives as a new approach for the production of secondary metabolites with remarkable biological benefits, which can be the precursors for novel biofortified and nutraceutical-enriched foods that meet the needs of the most demanding and health-conscious consumers.

RESUMO

Piper regnellii is a plant popularly known as "Pariparoba" and it is widely used in folk medicine to treat pain, inflammation, among others. This work presents the extraction, purification and characterization of polysaccharides present in the plant leaves and evaluation of their anti-inflammatory and antinociceptive activities. From the crude aqueous extract of P. regnellii leaves, a polysaccharide fraction named PR30R, predominantly constituted of arabinose, galactose and galacturonic acid monosaccharide units, was obtained. Methylation and NMR analysis showed that the main polysaccharides of PR30R are a type II arabinogalactan, formed by a ß-D-Galp-(1 â†’ 3) main chain, substituted at O-6 by side chains of ß-D-Galp-(1 â†’ 6), which are substituted at O-3 by non-reducing α-L-Araf ends, and a homogalacturonan, formed by →4)-α-D-GalpA-(1→ units. Intraperitoneal administration of the crude polysaccharide fraction PRSF reduced significantly nociception induced by acetic acid in mice at the doses tested, and the PR30R fraction, derived from PRSF, presented antinociceptive and anti-inflammatory effects at a dose of 0.1096 mg/kg (PRSF ED50). These data support the use of the plant leaves in folk medicine as an herbal tea to treat pain and inflammation.

Assuntos

Piper , Animais , Camundongos , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Polissacarídeos/análise , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/análise , Inflamação , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Folhas de Planta/química , Dor/tratamento farmacológico

RESUMO

Functional foods have recently generated a lot of attention among consumers looking for healthy options. Studies have examined yogurt with carao to increase health benefits and probiotic characteristics. It has been determined that carao fruit and camel milk have high phenolic compound and antioxidant activity concentrations. The objective of this study was to examine if carao (0, 1.3, 2.65, and 5.3 g/L) incorporated into yogurt enhances anti-inflammatory stimulus and antioxidant activity and impacts the physio-chemical and sensory properties of camel milk yogurt. HT-29 cells were used as a model of anti-inflammatory response, including cytokine responses of IL-8 and mRNA production of IL-1ß and TNF-α in gastric digested isolated fraction. In addition, pH, titratable acidity, Streptococcus thermophilus counts and Lactobacillus bulgaricus counts of camel yogurts were examined during the fermentation process in 0, 2.5, 5, and 7 h whereas viscosity, syneresis, and radical scavenging assay evaluations were determined at hour 7. Furthermore, a consumer study was performed. Compared to control samples, the incorporation of carao into yogurts did not lead to a significant (ρ > 0.05) difference in the pH. In contrast, titratable acidity (TA), viscosity, syneresis, and antioxidant capacity significantly increased with the inclusion of 2.65 and 5.3 g/L carao, while 5.3 g/L carao significantly (ρ < 0.05) increased the counts of both bacteria. The inflammatory response of IL-8 and the level of mRNA production of IL-1ß and TNF-α was significantly (ρ < 0.05) lower with 2.65 and 5.3 g/L carao yogurt compared to control camel yogurt. Sensory attributes were not impacted by the addition of 1.3 and 2.65 g/L carao. Carao could be a possible ingredient to consider when improving the nutrition value of yogurt.

RESUMO

OBJECTIVES: To evaluate the ability of the aqueous extract of Mitracarpus frigidus (MFAq) to inhibit lipid body formation and inflammatory mediator production in macrophages stimulated with lipopolysaccharide (LPS) and interferon gamma (IFN-γ). METHODS: MFAq was chemically characterized by ultrafast liquid chromatography/quadruple time-of-flight tandem mass spectrometry. The macrophages obtained from mice were incubated with MFAq. Cell viability and membrane integrity were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and propidium iodide assays, respectively. Moreover, NO, reactive oxygen species (ROS), transforming growth factor beta (TGF-ß), prostaglandin E2 (PGE2) levels and lipid bodies (LBs) were examined in macrophages that were stimulated with LPS and IFN-γ and treated with MFAq. Finally, molecular docking analysis was conducted to investigate the interaction of MFAq with the cyclooxygenase 2 (COX-2) enzyme. KEY FINDINGS: Chlorogenic acid, clarinoside, harounoside, rutin, kaempferol-3O-rutinoside and 2-azaanthraquinone were identified in MFAq. MFAq significantly inhibited NO, ROS and LBs, and did not affect the membrane integrity of macrophages. MFAq-treated cells showed significantly lower levels of TGF-ß and PGE2. Molecular docking demonstrated that the compounds found in MFAq are able to inhibit COX-2 by binding to important residues in the catalytic site. CONCLUSIONS: MFAq interferes with lipid metabolism in stimulated macrophages, leading to the reduction of important inflammatory mediators. Furthermore, MFAq can directly inhibit the COX-2 enzyme or inhibit its expression owing to its ability to reduce NO production.

Assuntos

Dinoprostona , Lipopolissacarídeos , Animais , Camundongos , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Lipopolissacarídeos/farmacologia , Metabolismo dos Lipídeos , Simulação de Acoplamento Molecular , Interferon gama/metabolismo , Fator de Crescimento Transformador beta/metabolismo

RESUMO

Chagas disease is a neglected tropical disease with only two drugs available for treatment and the plant Cecropia pachystachya has several compounds with antimicrobial and anti-inflammatory activities. This study aimed to evaluate a supercritical extract from C. pachystachya leaves in vitro and in vivo against Trypanosoma cruzi. A supercritical CO2 extraction was used to obtain the extract (CPE). Cytotoxicity and immunostimulation ability were evaluated in macrophages, and the in vitro trypanocidal activity was evaluated against epimastigotes and trypomastigotes forms. In vivo tests were done by infecting BALB/c mice with blood trypomastigotes forms and treating animals orally with CPE for 10 days. The parasitemia, survival rate, weight, cytokines and nitric oxide dosage were evaluated. CPE demonstrated an effect on the epi and trypomastigotes forms of the parasite (IC50 17.90 ± 1.2 µg/mL; LC50 26.73 ± 1.2 µg/mL) and no changes in macrophages viability, resulting in a selectivity index similar to the reference drug. CPE-treated animals had a worsening compared to non-treated, demonstrated by higher parasitemia and lower survival rate. This result was attributed to the anti-inflammatory effect of CPE, demonstrated by the higher IL-10 and IL-4 values observed in the treated mice compared to the control ones. CPE demonstrated a trypanocidal effect in vitro and a worsening in the in vivo infection due to its anti-inflammatory activity.

Assuntos

Doença de Chagas , Triterpenos , Tripanossomicidas , Trypanosoma cruzi , Camundongos , Animais , Parasitemia/tratamento farmacológico , Tripanossomicidas/farmacologia , Tripanossomicidas/uso terapêutico , Doença de Chagas/tratamento farmacológico , Trypanosoma cruzi/fisiologia , Camundongos Endogâmicos BALB C , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ácido Ursólico

RESUMO

Secondary metabolites such as flavonoids are promising in the treatment of non-alcoholic fatty liver disease (NAFLD), which is one of the complications of diabetes due to oxidative stress and inflammation. Some plants, such as Eryngium carlinae, have been investigated regarding their medicinal properties in in vitro and in vivo assays, showing favorable results for the treatment of various diseases such as diabetes and obesity. The present study examined the antioxidant and anti-inflammatory effects of the phenolic compounds present in an ethyl acetate extract of the inflorescences of Eryngium carlinae on liver homogenates and mitochondria from streptozotocin (STZ)-induced diabetic rats. Phenolic compounds were identified and quantified by UHPLC-MS. In vitro assays were carried out to discover the antioxidant potential of the extract. Male Wistar rats were administered with a single intraperitoneal injection of STZ (45 mg/kg) and were given the ethyl acetate extract at a level of 30 mg/kg for 60 days. Phytochemical assays showed that the major constituents of the extract were flavonoids; in addition, the in vitro antioxidant activity was dose dependent with IC50 = 57.97 mg/mL and IC50 = 30.90 mg/mL in the DPPH and FRAP assays, respectively. Moreover, the oral administration of the ethyl acetate extract improved the effects of NAFLD, decreasing serum and liver triacylglycerides (TG) levels and oxidative stress markers and increasing the activity of the antioxidant enzymes. Likewise, it attenuated liver damage by decreasing the expression of NF-κB and iNOS, which lead to inflammation and liver damage. We hypothesize that solvent polarity and consequently chemical composition of the ethyl acetate extract of E. carlinae, exert the beneficial effects due to phenolic compounds. These results suggest that the phenolic compounds of the ethyl acetate extract of E. carlinae have antioxidant, anti-inflammatory, hypolipidemic, and hepatoprotective activity.

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Eugenia uniflora leaf infusion is widely used in folk medicine to treat gastroenteritis, fever, hypertension, inflammatory and diuretic diseases. AIM OF THE STUDY: This work evaluated the acute oral toxic, antinociceptive, and anti-inflammatory activities of the curzerene chemotype of Eugenia uniflora essential oil (EuEO). MATERIAL AND METHODS: EuEO was obtained by hydrodistillation and analyzed by GC and GC-MS. The antinociceptive action in mice was evaluated for the peripheral and central analgesic activity using abdominal contortion and hot plate tests (50, 100, and 200 mg/kg); xylene-induced ear swelling was carried out for the nociception test, and carrageenan-induced cell migration test. Spontaneous locomotor activity was assessed in the open field test to rule out any nonspecific sedative or muscle relaxant effects of EuEO. RESULTS: The EuEO displayed a yield of 2.6 ± 0.7%. The major compounds classes were oxygenated sesquiterpenoids (57.3 ± 0.2%), followed by sesquiterpene hydrocarbons (16.4 ± 2.6). The chemical constituents with the highest concentrations were curzerene (33.4 ± 8.5%), caryophyllene oxide (7.6 ± 2.8%), ß-elemene (6.5 ± 1.8%), and E-caryophyllene (4.1 ± 0.3%). Oral treatment with EuEO, at doses of 50, 300, and 2000 mg/kg, did not change the behavior patterns or mortality of the animals. EuEO (300 mg/kg) did not cause a reduction in the number of crossings in the open field compared to the vehicle group. The aspartate aminotransferase (AST) level was higher in EuEO-treated groups (50 and 2000 mg/kg) when compared to the control group (p < 0.05). EuEO, at doses of 50, 100, and 200 mg/kg, reduced the number of abdominal writhings by 61.66%, 38.33%, and 33.33%. EuEO did not show increased hot plate test time latency in any of the intervals analyzed. At 200 mg/kg, EuEO decreased paw licking time, with inhibition of 63.43%. In formalin-induced acute pain, EuEO decreased paw licking time at doses of 50, 100, and 200 mg/kg in the first phase, with inhibition of 30.54%, 55.02%, and 80.87%. The groups treated with EuEO at doses of 50, 100, and 200 mg/kg showed ear edema reduction of 50.26%, 55.17%, and 51.31%, respectively. Moreover, EuEO inhibited leukocyte recruitment only at a dose of 200 mg/kg. The inhibitory values of leukocyte recruitment after 4 h of carrageenan application were 4.86%, 4.93%, and 47.25% for 50, 100, and 200 mg/kg of essential oil, respectively. CONCLUSION: The EuEO, curzerene chemotype, has significant antinociceptive and anti-inflammatory activities and low acute oral toxicity. This work confirms the antinociceptive and anti-inflammatory of this species as the traditional use.

Assuntos

Eugenia , Óleos Voláteis , Sesquiterpenos , Camundongos , Animais , Óleos Voláteis/farmacologia , Óleos Voláteis/uso terapêutico , Óleos Voláteis/química , Carragenina , Eugenia/química , Brasil , Dor/induzido quimicamente , Dor/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios/química , Analgésicos/farmacologia , Analgésicos/uso terapêutico , Analgésicos/química , Sesquiterpenos/uso terapêutico , Extratos Vegetais/efeitos adversos , Edema/induzido quimicamente , Edema/tratamento farmacológico

RESUMO

This study evaluated the effects of different drying methods (freeze drying, vacuum drying, infrared drying, convective drying, and sun drying) on the biological properties of berries from the Chilean murta (Ugni molinae Turcz) shrub. Physical-chemical properties (proximal composition, dietary fiber, sugars) were determined. Total phenolic content through the method of Folin-Ciocalteau, the profile of phenol compounds was determined by HPLC, and antioxidant potential by DPPH and ORAC assays were also evaluated. The topic anti-inflammatory effect was evaluated by mice´s ear edema, and in vitro anti-tumoral activity was tested by MTT assay. The chemical properties of dried berries differed significantly based on the drying method: freeze-dried murta berries showed increased total phenolic content extracted over fresh and dried samples. In addition, this lyophilized extract stood out in its antioxidant potential, in both assays evaluated (DPPH and ORAC), compared to the other drying methods. Notwithstanding, vacuum- and infrared-dried murta also showed a higher ORAC value. Antioxidant potential was significantly associated with phenolic compounds catechin and pyrogallol, which were the most abundant phenolic compounds present in all samples. The anti-inflammatory activity was most effective under freeze-drying and vacuumdrying conditions. Moreover, vacuum drying and infrared drying best preserved the anti-tumoral effect on cancer cells.

RESUMO

The health-related compounds present in kale are vulnerable to the digestive process or storage conditions. Encapsulation has become an alternative for their protection and takes advantage of their biological activity. In this study, 7-day-old Red Russian kale sprouts grown in the presence of selenium (Se) and sulfur (S) were spray-dried with maltodextrin to assess their capacity to protect kale sprout phytochemicals from degradation during the digestion process. Analyses were conducted on the encapsulation efficiency, particle morphology, and storage stability. Mouse macrophages (Raw 264.7) and human intestinal cells (Caco-2) were used to assess the effect of the intestinal-digested fraction of the encapsulated kale sprout extracts on the cellular antioxidant capacity, the production of nitric oxide (NOx), and the concentrations of different cytokines as indicators of the immunological response. The highest encapsulation efficiency was observed in capsules with a 50:50 proportion of the hydroalcoholic extract of kale and maltodextrin. Gastrointestinal digestion affected compounds' content in encapsulated and non-encapsulated kale sprouts. Spray-dried encapsulation reduced the phytochemicals' degradation during storage, and the kale sprouts germinated with S and Se showed less degradation of lutein (35.6%, 28.2%), glucosinolates (15.4%, 18.9%), and phenolic compounds (20.3%, 25.7%), compared to non-encapsulated ones, respectively. S-encapsulates exerted the highest cellular antioxidant activity (94.2%) and immunomodulatory activity by stimulating IL-10 production (88.9%) and COX-2 (84.1%) and NOx (92.2%) inhibition. Thus, encapsulation is an effective method to improve kale sprout phytochemicals' stability and bioactivity during storage and metabolism.