Oral delivery of fish oil in oil-in-water nanoemulsion: development, colloidal stability and modulatory effect on in vivo inflammatory induction in mice.

To improve the oral absorption of fish oil and test its anti-inflammatory effect, a fish oil nanoemulsion was developed using cis-4,7,10,13,16,19-docosahexaenoic fatty acid as a biomarker for oral administration. The colloidal stability tests of the fish oil nanoemulsion showed an average size of 155.44 nm ±â€¯6.46 (4 °C); 163.04 nm ±â€¯9.97 (25 °C) and polydispersity index 0.22 ±â€¯0.02 (4 °C), 0.21 ±â€¯0.02 (25 °C), indicating systems with low polydispersity and stable droplets. The fish oil nanoemulsion did not alter the cell viability of the RAW 264.7 macrophages and, at a concentration of 0.024 mg/mL, was kinetically incorporated into the cells after 18 h of contact. The nanoemulsion was maintained in the gastrointestinal region for a significantly shorter period of time (p ≤ 0.05) compared to the intake of fish oil in free form. Inflammatory tests demonstrated that nanoemulsion and fish oil showed less (p ≤ 0.05) neutrophil infiltration after 24h of sepsis induction and there was a significant reduction (p ≤ 0.05) in the volume of paw edema in female adult Balb/c mice who received the nanoemulsion diet compared to the other experimental groups (control, formalin, fish oil and sunflower oil). These results indicate that the fish oil nanoemulsion was significantly effective in the dietary conditions tested here, presenting satisfactory responses in the modulation of inflammatory disorders, demonstrating interesting and beneficial nutraceutical effects.

Effects of 2-Hydroxypropil-Β-Cyclodextrin-Lidocaine on Tumor Growth and Inflammatory Response.

BACKGROUND: Antiproliferative and cytotoxic effects of lidocaine have been reported in tumor cells. However, the use of these drugs is restricted due to their short action with rapid dispersion from the injected site. The complexation of local anesthetics in 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) is able to improve pharmacological features. OBJECTIVE: This study evaluated the antitumor effects of lidocaine and the complex HP-ß-CD-lidocaine (HP-ß-CD-lido). METHODS: In vitro;, human adenocarcinoma (HeLa) and keratinocytes (HaCaT) were exposed to lidocaine formulations and cell viability, proliferation and apoptosis induction were measured. In vivo;, Walker 256 carcinoma cells were subcutaneously injected into the plantar region of the rat right hind paw. The animals were treated with a local application of 5% lidocaine or 5% HP-ß-CD-lido. Doxorubicin (3 mg/Kg/day, intraperitoneal) was used as a positive control. Edema sizes were measured daily and the release of cytokines (TNF-α, IL-1α and CXCL-1) and prostaglandin E2 was evaluated. Histological analysis was also performed. RESULTS: HaCaT IG50 values were 846 µM and 2253 µM for lido and HP-ß-CD-lido, respectively. In HeLa cells, the IG50 was 1765 µM for lido and 2044 µM for HP-ß-CD-lido. Lidocaine formulations significantly reduced the paw edema on day 6 after Walker 256 cells inoculation. However, there were no differences in the release of inflammatory mediators in comparison to the control group. CONCLUSION: Lidocaine formulations were able to reduce the edema in vivo;, without affecting the tumor- induced inflammatory response. The antiproliferative effects of lidocaine formulations may have contributed to tumor reduction.

Inflammatory Reaction Induced by Two Metalloproteinases Isolated from Bothrops atrox Venom and by Fragments Generated from the Hydrolysis of Basement Membrane Components.

Snake venom metalloproteinases (SVMPs) play an important role in local tissue damage of snakebite patients, mostly by hydrolysis of basement membrane (BM) components. We evaluated the proinflammatory activity of SVMPs Atroxlysin-Ia (ATXL) and Batroxrhagin (BATXH) from Bothrops atrox venom and their hydrolysis products of Matrigel. BALB/c mice were injected with SVMPs (2 µg), for assessment of paw edema and peritoneal leukocyte accumulation. Both SVMPs induced edema, representing an increase of ~70% of the paw size. Leukocyte infiltrates reached levels of 6 × 106 with ATXL and 5 × 106 with BATXH. TNF-α was identified in the supernatant of BATXH-or venom-stimulated MPAC cells. Incubation of Matrigel with the SVMPs generated fragments, including peptides from Laminin, identified by LC-MS/MS. The Matrigel hydrolysis peptides caused edema that increased 30% the paw size and promoted leukocyte accumulation (4-5 × 106) to the peritoneal cavity, significantly higher than Matrigel control peptides 1 and 4 h after injection. Our findings suggest that ATXL and BATXH are involved in the inflammatory reaction observed in B. atrox envenomings by direct action on inflammatory cells or by releasing proinflammatory peptides from BM proteins that may amplify the direct action of SVMPs through activation of endogenous signaling pathways.

Corticoid-like anti-inflammatory effect of Vochysia bifalcata Warm.: Preclinical evidence of efficacy and safety.

ETHNOPHARMACOLOGICAL RELEVANCE: Vochysia bifalcata is a Brazilian native tree commonly used for economic purpose in the reforestation and in the manufacture of products. However, the potential usage of other parts of the plant is usually wasted. Besides, other species of Vochysia are well known for its anti-inflammatory action. AIM OF THE STUDY: In this study we evaluate the possible anti-inflammatory activity of the hydroethanolic extract from the leaves of V. bifalcata in models of mice skin inflammation. MATERIALS AND METHODS: Effects of V. bifalcata were evaluated in croton oil-induced acute and chronic skin inflammation. The role of glucocorticoid receptors in the extract effect was assessed by using a glucocorticoid receptor antagonist and by a specific binding assay. Possible adverse effects were evaluated after multiple treatments with the extract in a skin atrophy model. RESULTS: Topical application of V. bifalcata reduced ear edema formation, cell infiltration and interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels. In the chronic model, besides edema formation and cell infiltration, the extract inhibited epidermal hyperproliferation and Proliferating Cell Nuclear Antigen expression. V. bifalcata seems to act by biding to corticoid receptors, however it did not induce corticoid related undesirable effects. CONCLUSION: Hydroethanolic extract from leaves of V. bifalcata could be an interesting tool in the search for new anti-inflammatory and antiproliferative agents for the treatment of skin disorders.

Anti-Inflammatory Derivatives with Dual Mechanism of Action from the Metabolomic Screening of Poincianella pluviosa.

Metabolomics approaches have become fundamental strategies for the analysis of complex mixtures, guiding the isolation of target compounds by focusing on unpublished or promising pharmacological properties. The discovery of novel anti-inflammatory agents is important due to several limitations regarding their potency, efficacy, and adverse effects. Thus, novel anti-inflammatory candidates are essential, aiming to find agents with better mechanisms of action. In this context, extracts from Poincianella pluviosa var. peltophoroides demonstrated significant in vivo anti-inflammatory potential. Thus, metabolomics analysis based on UHPLC-UV-HRFTMS data was performed for the identification of biomarkers with anti-inflammatory properties. Metabolomics-guided chromatographic process led to the isolation of novel compounds 4‴-methoxycaesalpinioflavone and 7-methoxycaesalpinioflavone, as well as known derivatives rhuschalcone VI and caesalpinioflavone. Isolated compounds caused edema inhibition and neutrophil recruitment. Two of them showed better efficacy than reference drugs (indomethacin and dexamethasone). Results of in vivo experiments corroborated those obtained through metabolomics and statistical analyses guiding the isolation of substances of interest.

Effects of Eugenia umbelliflora O. Berg (Myrtaceae)-leaf extract on inflammation and hypersensitivity.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Eugenia species are widely used in popular medicine to treat several diseases, such as arthritis, rheumatism and diabetes. Eugenia umbelliflora O. Berg is popularly known in Brazil as "baguaçu", name also conferred to Eugenia jambolana probably due to their apparent similarity. Although the popular use scientifically proved of E. jambolana as anti-diabetes and also as anti-inflammatory, there are only two scientific studies demonstrating anti-ulcer and bactericide activities of E. umbelliflora leaves extract, without reference to its possible anti-inflammatory activity. AIM OF THE STUDY: The aim of this study was to show the anti-oxidant and anti-inflammatory activity of the methanol extract obtained from E. umbelliflora leaves (EuL) using in vitro and in vivo protocols. MATERIALS AND METHODS: The total phenolic content was evaluated using the folin-Ciocalteu colorimetric method and phloroglucinols content by HPLC. The anti-oxidant activity was evaluated by ORAC, ABTS•+, DPPH, and metal chelation methods. The anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice orally pre-treated with the EuL (0.3, 1 or 3 mg/kg). The leukocyte influx (optical microscopy) and secretion of chemical mediators (TNF, IL-6, IL-1ß and CXCL1, by enzyme-linked immunosorbent assay) were quantified in the inflamed exudate. Histological analysis of the pouches was also performed. The anti-hypersensitive activity was investigated using carrageenan-induced mechanical hypersensitivity and mice were then evaluated using the von Frey filaments. The Open Field test was used to evaluate possible interference of adverse effect of EuL on locomotor activity that could lead to misinterpretation of the hypersensitivity evaluation. RESULTS: The EuL demonstrated important and moderate reducing capacity on ABTS•+ and DPPH assays, respectively, but with slight activity in ORAC test. It reflects low protection against cell damage. The EuL also presented 30% of phenolic compounds. The phloroglucinols content of EuL was 25.9 mg/g, 18.4 mg/g and 16.6 mg/g of eugenial C, eugenial D and eugenial E, respectively. The in vivo analysis of the inflammatory exudate of EuL-treated mice demonstrated reduction in the polymorphonuclear cells (PMN) migration to the inflamed tissue, as well as the reduction of the pro-inflammatory cytokine IL-1ß. Histologically, it was observed evident decrease in the oedema, formed essentially by non-haemorrhagic fibrin exudate, as well as PMN infiltrate, when compared with control mice injected with carrageenan. Furthermore, the extract also presented effective reduction of the mechanical hypersensitivity induced by carrageenan without any interference in animal's locomotor and exploratory activity. CONCLUSIONS: Together, the results herein obtained show that EuL presented anti-inflammatory activity by decreasing the influx of PMN to the inflamed tissue, as well as the cytokine IL-1ß level. This anti-inflammatory activity was also accompanied by significant anti-hypersensitive effect. The effects presented by EuL seem not to be correlated with an antioxidant activity. However other extract chemical compounds could be responsible for its important anti-inflammatory effects.

Evaluation of inflammatory skin infiltrate following Aedes aegypti bites in sensitized and non-sensitized mice reveals saliva-dependent and immune-dependent phenotypes.

During probing and blood feeding, haematophagous mosquitoes inoculate a mixture of salivary molecules into their vertebrate hosts' skin. In addition to the anti-haemostatic and immunomodulatory activities, mosquito saliva also triggers acute inflammatory reactions, especially in sensitized hosts. Here, we characterize the oedema and the cellular infiltrate following Aedes aegypti mosquito bites in the skin of sensitized and non-sensitized BALB/c mice by flow cytometry. Ae. aegypti bites induced an increased oedema in the ears of both non-sensitized and salivary gland extract- (SGE-)sensitized mice, peaking at 6 hr and 24 hr after exposure, respectively. The quantification of the total cell number in the ears revealed that the cellular recruitment was more robust in SGE-sensitized mice than in non-sensitized mice, and the histological evaluation confirmed these findings. The immunophenotyping performed by flow cytometry revealed that mosquito bites were able to produce complex changes in cell populations present in the ears of non-sensitized and SGE-sensitized mice. When compared with steady-state ears, the leucocyte populations significantly recruited to the skin after mosquito bites in non-sensitized and sensitized mice were eosinophils, neutrophils, monocytes, inflammatory monocytes, mast cells, B-cells and CD4+ T-cells, each one with its specific kinetics. The changes in the absolute number of cells suggested two cell recruitment profiles: (i) a saliva-dependent migration; and (ii) a migration dependent on the immune status of the host. These findings suggest that mosquito bites influence the skin microenvironment by inducing differential cell migration, which is dependent on the degree of host sensitization to salivary molecules.

Natural chromones as potential anti-inflammatory agents: Pharmacological properties and related mechanisms.

Chromones are a group of natural substances with a diversity of biological activities. Herein we assessed the pharmacological potential of three chromones (1, 2 and 3) isolated from Dictyoloma vandellianum as anti-inflammatory agents using in vitro and in vivo approaches. During in vitro screening, the production of NO and cytokines by macrophages stimulated with LPS and IFN-γ was inhibited by all chromones at concentrations (5-20 µM) that did not induce cytotoxicity. Analysis of pharmacokinetic parameters (in vitro half-life and intrinsic clearance) using human liver microsomes revealed that 3 has a superior pharmacokinetic profile, compared to 1 and 2. Treatment with 3 (100 mg/kg, ip) did not affect the mice motor performance, while 1 and 2 induced motor deficit. Taking into account the pharmacokinetic profile and absence of motor impairment, 3 was selected for further pharmacological characterization. Corroborating the data from in vitro screening, treatment of cell cultures with 3 (5-20 µM) reduced TNF-α, IL-6 and IL-1ß production by stimulated macrophages. In the complete Freund's adjuvant-induced paw inflammation model in mice, 3 (25 and 50 mg/kg, ip) inhibited mechanical hyperalgesia, edema and cytokine production/release (IL-1ß, IL-6 and TNF-α). 3 (5-20 µM) also reduced the transcriptional activity of NF-κB in stimulated macrophages. Furthermore, treatment with RU486, a glucocorticoid receptor (GR) antagonist, partially prevented the inhibitory effect of 3 on macrophages, indicating that this chromone exerts its anti-inflammatory effects in part through the activation of GR. The results presented herein demonstrate the pharmacological potential of natural chromones, highlighting 3 as a possible candidate for the drug discovery process targeting new anti-inflammatory drugs.

Cerebrolysin improves peripheral inflammatory pain: Sex differences in two models of acute and chronic mechanical hypersensitivity.

Chronic inflammatory pain is a major health problem worldwide with high prevalence in women. Cerebrolysin is a multimodal neuropeptide preparation that crosses the blood brain barrier and displays neuroprotective properties in aging and disease. Previously, we showed that cerebrolysin reduced mechanical allodynia in a model of persistent inflammation and pain. We aim to build upon the findings of our previous study by investigating the response to acute administration of cerebrolysin in two models of peripheral inflammation and assessing sex differences. We utilized the complete Freund's adjuvant (CFA) that produces maximal oedema and mechanical allodynia within days and carrageenan that produces similar effects within hours. Cerebrolysin reversed the mechanical allodynia in both sexes in CFA-treated rats. On the other hand, in rats treated with carrageenan, cerebrolysin was only effective in reducing mechanical allodynia in female rats. In conclusion, the present study shows that cerebrolysin effects may be sex-specific depending on different mechanisms that are at play in these two models of peripheral inflammatory pain. Further investigations are required to determine the factors contributing to sex differences.

Chemical composition and evaluation of the anti-inflammatory and antinociceptive activities of Duguetia furfuracea essential oil: Effect on edema, leukocyte recruitment, tumor necrosis factor alpha production, iNOS expression, and adenosinergic and opioidergic systems.

ETHNOPHARMACOLOGICAL RELEVANCE: Duguetia furfuracea (A. St. -Hil.) Saff. (Annonaceae) is commonly known in Brazil as "araticum-seco," and its root is used in folk medicine to treat inflammatory and painful disorders. However, no studies have been performed to evaluate these therapeutic activities. AIM OF THE STUDY: Investigate the chemical composition, anti-inflammatory and antinociceptive effects, and elucidate the possible antinociceptive mechanisms of action from the essential oil of D. furfuracea (EODf) underground stem bark. MATERIALS AND METHODS: Chemical composition was determined by gas chromatography and mass spectrometry (GC/MS). The paw edema induced by LPS, formalin-induced nociception, LPS-induced thermal hyperalgesia and rota-rod tests in vivo were used to evaluate the anti-inflammatory and antinociceptive effects in addition to the alteration on motor coordination. Histological analyses and an immunohistochemistry assay for iNOS were performed on mouse footpads of naive, control, 10 mg/kg EODf, and 10 mg/kg indomethacin (Ind) groups. The samples were removed at 1, 3, and 6 h after subplantar injection of LPS. In addition, the involvement of the adenosinergic, opioidergic, serotonergic, and cholinergic systems were investigated, in order to elucidate possible antinociceptive mechanisms. RESULTS: Twenty-four volatile constituents were detected and identified. (E)-asarone (21.9%), bicyclogermacrene (16.7%), 2,4,5-trimethoxystyrene (16.1%), α-gurjunene (15%), cyperene (7.8%), and (E)-caryophyllene (4.6%) were major compounds found in EODf. Oral treatment (p.o.) with EODf (1, 3, and 10 mg/kg) significantly inhibited the paw edema induced by LPS. At 10 mg/kg EODf promoted inhibition of tumor necrosis factor alpha (TNF-α) production, recruitment of polymorphonuclear (PMN) leukocytes and inducible nitric oxide synthase (iNOS) expression in paw tissue. EODf (10 and 30 mg/kg, p.o.) also reduced licking time in both phases of the formalin test and it had a significant effect on the LPS-induced thermal hyperalgesia model. The administration of caffeine (Caf) and naloxone (Nal) reversed the antinociceptive activity of EODf, in the first phase of the formalin test and in the LPS-induced thermal hyperalgesia model. Moreover, Nal was also able to abolish the antinociception caused by EODf, in the second phase of formalin test. In the rota-rod test, EODf-treated animals did not show any alteration of motor coordination. CONCLUSIONS: Our findings indicate that EODf underground stem bark produces anti-inflammatory and both central and peripheral antinociceptive effects. Furthermore, the antinociceptive activity of EODf underground stem bark is possibly mediated by adenosinergic and opioidergic pathways, and its properties do not induce effects on motor coordination. These results support the use of the folk medicine, D. furfuracea root, to treat inflammation and painful conditions.

Tabernaemontana catharinensis leaves exhibit topical anti-inflammatory activity without causing toxicity.

BACKGROUND: Tabernaemontana catharinensis, popularly known as snake skin, has been empirically used as an anti-inflammatory to treat cutaneous skin disorders. However, no study proves its effectiveness as a topical anti-inflammatory. STUDY DESIGN: We investigated the topical anti-inflammatory effect of T.catharinensis leaves crude extract (TcE) in irritant contact dermatitis models in mice and its preliminary toxicity profile. METHODS: The topical anti-inflammatory effect was evaluated by ear thickness measurement, inflammatory cell infiltration (MPO activity measurement and histological procedure) and cytokines levels. TcE qualitative phytochemical analysis was performed by UHPLC-ESI-HRMS and the TcE effect (therapeutic dose; 10 µg/ear) on preliminary toxicological parameters was also evaluated (on the 14°â€¯day of experiment). RESULTS: TcE (10 µg/ear) prevented the development of ear edema induced by cinnamaldehyde, capsaicin, arachidonic acid, phenol, and croton oil with maximum inhibition of 100% to cinnamaldehyde, arachidonic acid, phenol, and croton oil and 75 ±â€¯6% to capsaicin. Besides, the TcE (10 µg/ear) also prevented the increase of MPO activity by 96 ±â€¯2%, 48 ±â€¯7%, 100%, 87 ±â€¯8%, and 93 ±â€¯4%, respectively, to the same irritant agents. The positive controls also prevented both ear edema and the increased of MPO activity by 100% and 42 ±â€¯8% (HC-030031), 54 ±â€¯6% and 80 ±â€¯4% (SB-366791), 100% and 54 ±â€¯5% (indomethacin), 100% and 80 ±â€¯4% (dexamethasone in skin inflammation model induced by phenol) and 100% and 97 ±â€¯3% (dexamethasone in inflammation model induced by croton oil), respectively. TcE also prevented the inflammatory cells infiltration and the increase of MIP-2, IL-1ß and TNF-α levels irritant agents-induced. TcE topical anti-inflammatory effect may be attributed to the combined effect of indole alkaloids, terpenes, and phenolic compounds found in the extract and identified by dereplication method. The TcE' therapeutic dose proved to be safe in preliminary toxicological tests. CONCLUSION: Our results suggest that TcE could be an interesting strategy for the treatment of inflammatory diseases.

Systemic treatment with resveratrol reduces the progression of experimental periodontitis and arthritis in rats.

Rheumatoid arthritis and periodontitis are chronic inflammatory diseases which has been closely associated due to the nature of immune-inflammatory imbalance response. Resveratrol is a naturall product with biological proprieties that may promote immunomodulatory effects on host response. This study investigated resveratrol continuous administration effect on experimental periodontitis and arthritis progression in rats. Thirty-five rats were assigned to the following groups: 1-experimental arthritis + experimental periodontitis + placebo (RA+EP +PL) (n = 12); 2 -RA+EP+ ibuprofen (RA+PE+IB) (n = 11); 3-RA+EP+ resveratrol (RA+PE+RSV) (n = 11). After euthanasia, the specimens were processed for morphometric analysis of bone loss, and the gingival tissue surrounding the first molar was collected for quantification of inflammatory markers using a Luminex/MAGpix assay and anti-citrullinated protein antibody (ACCPA) levels were measured by ELISA assay. Serum level of rheumatoid factor (RF) was measured by ELISA assay. Paw edema was analyzed using a plethysmometer. Higher bone loss was observed in PL group, when compared to IB and RSV groups. RSV group presented higher IL-4 concentration than PL and IB groups. Resveratrol reduced RF serum levels and both IB and RSV decreased ACCPA gingival levels. Besides, paw swelling level was significantly lower in IB and RSV groups in the 21th day and only in RSV group in the 28th day. Histological analyzes showed smooth articular surface and higher width of the subchondral cortical in RSV group. Resveratrol showed modulatory effect and seems to reduce the inflammatory signs of arthritis and articular damage throughout the time.

Collagen V oral administration decreases inflammation and remodeling of synovial membrane in experimental arthritis.

Because collagen type V (Col V) can be exposed in tissue injury, we hypothesized that oral administration of this collagen species modulates the inflammation and remodeling of experimental synovitis, avoiding joint destruction, and that the modulation may differ according to the temporal administration. Arthritis (IA, n = 20) was induced in Lewis rats by intraarticular (ia) injection of 500 µg of methylated bovine serum albumin (mBSA) emulsified in complete Freund's adjuvant (CFA) (10 µl) followed by an intraarticular booster of mBSA (50 µg) in saline (50 µl) administered at 7 and 14 days. The control group received saline (50 µl, ia). After the first intraarticular injection, ten IA animals were supplemented via gavage with Col V (500 µg/300 µl) daily for 30 days (IA/Suppl). The control group received saline (50 µL) and Col V supplement in the same way (Suppl). Col V oral administration in IA/Suppl led to 1) inhibited edema and severe inflammatory cell infiltration, 2) decreased collagen fiber content, 3) decreased collagen type I, 4) inhibited lymphocyte subpopulations and macrophages, 5) inhibited IL-1ß, IL-10, IL-17 and TNF-α production and 6) increased expression of caspase-9 in the synovial tissue. In conclusion, Col V supplementation decreased synovial inflammation and the fibrotic response, possibly by increased the apoptosis of inflammatory cells.

Establishment and Phytochemical Analysis of a Callus Culture from Ageratina pichinchensis (Asteraceae) and Its Anti-Inflammatory Activity.

A protocol was established to produce bioactive compounds in a callus culture of Ageratina pichinchensis by using 1 mg L-1 NAA with 0.1 mg L-1 KIN. The phytochemical study of the EtOAc extract obtained from the callus biomass, allowed the isolation and characterization of eleven secondary metabolites, of which dihydrobenzofuran (5) and 3-epilupeol (7), showed important anti-inflammatory activity. Compound 5 inhibits in vitro the secretion of NO (IC50 = 36.96 ± 1.06 µM), IL-6 (IC50 = 73.71 ± 3.21 µM), and TNF-α (IC50 = 73.20 ± 5.99 µM) in RAW (Murine macrophage cells) 264.7 macrophages, as well as the activation of NF-κB (40% at 150 µM) in RAW-blue macrophages, while compound 7 has been described that inhibit the in vivo TPA-induced ear edema, and the in vitro production of NO, and the PLA2 enzyme activity. In addition, quantitative GC-MS analysis showed that the anti-inflammatory metabolites 5 and 7 were not detected in the wild plant. Overall, our results indicated that A. pichinchensis can be used as an alternative biotechnological resource for obtaining anti-inflammatory compounds. This is the first report of the anti-inflammatory activity of compound 5 and its production in a callus culture of A. pichinchensis.

Evaluation of the in vivo acute antiinflammatory response of curcumin-loaded nanoparticles.

Curcumin is the main curcuminoid found in turmeric rhizomes and is a strong candidate to formulate foodstuff with specific properties. Among various bioactive properties of curcumin, its antiinflammatory activity is remarkable; on the other hand, its low water solubility leads to low absorption. Thus, new formulations need to be developed to improve its efficacy, and encapsulation is a promising alternative strategy in this regard. The objective of the present study was to obtain curcumin-loaded polyvinylpyrrolidone (PVP) nanoparticles and evaluate their acute in vivo antiinflammatory activity. Nanoparticles were obtained by complexation using the solid dispersion technique, and the characterization of nanoparticles showed that curcumin and PVP formed an amorphous solid solution. Encapsulated curcumin was colloidally stable in distilled water; this was attributed to the formation of hydrogen bonds between curcumin hydroxyl and PVP carbonyl groups. Rats were treated orally with single doses of curcumin and curcumin-loaded PVP nanoparticles, and antiinflammatory activity was evaluated by an experimental model of carrageenan-induced paw edema, myeloperoxidase (MPO) activity, and microcirculation in situ. Treatment with nanoparticles at 12.5 mg kg-1 significantly reduced the intensity of edema and MPO activity, whereas pure curcumin only presented a significant effect at 400 mg kg-1. Curcumin inhibited cell migration since rolling and adherent leukocytes were significantly reduced using nanoparticles at 50 mg kg-1 and curcumin at 400 mg kg-1. Compared to free curcumin, encapsulated curcumin was effective at lower doses; this might be due to the improved water affinity and colloidal stability of curcumin nanoparticles.

Lycopene rich extract from red guava (Psidium guajava L.) displays anti-inflammatory and antioxidant profile by reducing suggestive hallmarks of acute inflammatory response in mice.

This study investigated the anti-inflammatory activity of the extract (LEG) and purified (LPG) lycopene from guava (Psidium guajava L.), as well as some mechanisms possibly involved in this effect. The anti-inflammatory activity was initially assessed using paw edema induced by Carrageenan, Dextran, Compound 48/80, Histamine and Prostaglandin E2 in Swiss mice. A peritonitis model was used to evaluate neutrophil migration, the activity of myeloperoxidase (MPO) and reduced glutathione (GSH) concentration; while the effect on the expression of iNOS, COX-2 and NF-κB, was assessed by immunohistochemistry analysis. Results showed that oral and intraperitoneal administration of LEG and LPG inhibited inflammation caused by carrageenan. LPG (12.5mg/kg p.o.) significantly inhibited the edema formation induced by different phlogistic agents and immunostaining for iNOS, COX-2 and NF-κB. Leukocytes migration in paw tissue and peritoneal cavity was reduced, as well as MPO concentration, whereas GSH levels increased. Thus, lycopene-rich extract from red guava has beneficial effect on acute inflammation, offering protection against the consequences of oxidative stress by downregulating inflammatory mediators and inhibiting gene expression involved in inflammation.

Probucol attenuates overt pain-like behavior and carrageenan-induced inflammatory hyperalgesia and leukocyte recruitment by inhibiting NF-кB activation and cytokine production without antioxidant effects.

OBJECTIVE AND DESIGN: This study aimed to evaluate the effect of probucol in inflammatory hyperalgesia and leukocyte recruitment in mice. TREATMENT: Probucol at 0.3-3 mg/kg was administrated per oral 1 h before inflammatory stimulus.Author: Kindly check and confirm the affiliation 1 have been correctly processed or not and amend if necessary.Thank you. We have corrected affiliation 1. We added the information to the appropriate boxes. However the state and the postal code are in a different order when compared to the other affiliations. METHODS: Overt pain-like behaviors were determined by the number of abdominal writhings induced by phenyl-p-benzoquinone and acetic acid. Mechanical and thermal hyperalgesia induced by carrageenan were determined using an electronic anesthesiometer and hot plate apparatus, respectively. Leukocyte recruitment was evaluated by direct count or by determination of myeloperoxidase and N-acetylglucosaminidase activities. Antioxidant ability was determined by measurement of GSH levels, ABTS and FRAP assays. Cytokine production and NF-кB activation were evaluated by ELISA. Data were analyzed by ANOVA followed by Tukey's post-hoc. p < 0.05 was considered significant. RESULTS: Probucol reduced overt pain-like behavior, and carrageenan-induced mechanical and thermal hyperalgesia. These effects were accompanied by reduced leukocyte influx in both paw skin and peritoneum exudate. Probucol did not alter carrageenan-induced tissue antioxidant capacity at anti-inflammatory/analgesic dose. On the other hand, probucol inhibited carrageenan-induced IL-1ß, TNF-α and CXCL1 production as well as NF-кB activation. CONCLUSION: Probucol presents analgesic and anti-inflammatory activities by employing mechanisms other than its antioxidant properties. These mechanisms involve targeting of pro-inflammatory cytokines and NF-кB activation.

Anti-inflammatory activity of the essential oil obtained from Ocimum basilicum complexed with ß-cyclodextrin (ß-CD) in mice.

Cyclodextrins (CDs) are cyclic oligosaccharides can enhance the bioavailability of drugs. Ocimum basilicum is an aromatic plant found in Brazil used in culinary. The essential oil of this plant presents anti-edematogenic and anti-inflammatory activities in acute and chronic inflammation. The aim of this study was to investigate the anti-inflammatory effects of the essential oil obtained from O. basilicum complexed with ß - cyclodextrin (OBEO/ß-CD) in mice. The complexation with ß-cyclodextrin (ß-CD) was performed by different methods and analyzed by differential scanning calorimetry (DSC), thermogravimetry (TG) and scanning electron microscopy (SEM). The anti-inflammatory activity was evaluated using mice models of paw edema induced by carrageenan, dextran, histamine and arachidonic acid (AA); vascular permeability and peritonitis induced by carrageenan and granuloma induced by cotton block introduction. The DSC, TG and SEM analysis indicated that the OBEO was successfully complexed with ß-CD. The oral administration of OEOB/ß-CD prevented paw edema formation by decreasing vascular permeability in vivo, inhibited leukocyte recruitment to the peritoneal cavity, and inhibited granuloma formation in mice. Our results indicate that conjugation with ß-CD improves the anti-inflammatory effects of OBEO in mice models of acute and chronic inflammation, indicating that this complex can be used in anti-inflammatory drug development.

Active immunization of cattle with a bothropic toxoid does not abrogate envenomation by Bothrops asper venom, but increases the likelihood of survival.

This study assessed the protective effect of active immunization of cattle to prevent the envenomation induced by B. asper venom. Two groups of oxen were immunized with a bothropic toxoid and challenged by an intramuscular injection of either 10 or 50 mg B. asper venom, to induce moderate or severe envenomations, respectively. Non-immunized oxen were used as controls. It was found that immunized oxen developed local edema similar to those observed in non-immunized animals. However, systemic effects were totally prevented in immunized oxen challenged with 10 mg venom, and therefore antivenom treatment was not required. When immunized oxen were challenged with 50 mg venom, coagulopathy was manifested 3-16 h later than in non-immunized oxen, demonstrating a delay in the onset of systemic envenomation. In these animals, active immunization did not eliminate the need for antivenom treatment, but increased the time lapse in which antivenom administration is still effective. All experimentally envenomed oxen completely recovered after a week following venom injection. Our results suggest that immunization of cattle with a bothropic toxoid prevents the development of systemic effects in moderate envenomations by B. asper, but does not abrogate these effects in severe envenomation.