Fatty acid profile, physicochemical composition and carcass traits of young Nellore bulls fed Acacia mearnsii extract.

Fatty acid profile, physicochemical composition, and carcass traits of 32 young Nellore bulls were assessed following the supplementation of Acacia mearnsii extract at levels of 0, 10, 30, and 50 g/kg of total dry matter (DM) in a completely randomized experiment with four treatments and eight replicates. Adding 50 g/kg DM of condensed tannins (CT) from Acacia mearnsii in the bulls' diet reduced DM intake, average daily gain, and meat lipid oxidation (P ≤ 0.05). The pH, centesimal composition, collagen, and meat color indexes of the longissimus muscle were not altered by the addition of Acacia mearnsii (P > 0.05). Cooling loss increased (P = 0.049) linearly. Including Acacia mearnsii in diet reduced the Warner-Bratzler shear force (WBSF, P = 0.018) of longissimus muscle of the bulls. The concentration of C16:0, C17:0, C24:0, t9,10,11,16-18:1, c9t11-18:2, C18:2n-6, C20:4n-6, 20:5n-3, 22:5n-3, and 22:6n-3 in the muscle increased due to the addition of Acacia in the diet (P ≤ 0.05), with the highest muscle concentrations caused by the addition of 10 to 30 g Acacia. c9-18:1 and t16-18:1 reduced linearly. Æ©SFA, Æ©BI, Æ©cis- and Æ©MUFA, Æ©n-3, Æ©n-6, and Æ©PUFA (P ≤ 0.05) quadratically increased at higher concentrations of addition of Acacia, above 30 g/kg DM. It is recommended to include Acacia mearnsii extract up to 30 g/kg total DM in diets for young bulls as it improves CLA, PUFA and TI and reduces lipid oxidation. Acacia mearnsii extract as source of CT at 50 g/kg DM negatively impacted the young bulls performance.

Production, characterization, and dietary supplementation effect of rumen-protected fat on ruminal function and blood parameters of sheep.

Rumen-protected fat (RPF) was produced in the 1st experimental stage through melt-emulsification technique using buriti oil (BO) as core, at concentrations of 10% (BO10), 20% (BO20), and 30% (BO30) (w/w), and carnauba wax (CW) as encapsulant material. After obtention and characterization, protected fat microspheres were tested in a 2nd experimental stage on the sheep' diet using six castrated 2-year-old male Santa Ines with initial weight 48.9 ± 5.23 kg, fistulated in rumen and distributed in a double Latin square design with 3 treatments × 3 periods, to evaluate rumen pH, temperature, protozoal count, and blood parameters. There was no difference (P > 0.05) among RPF microspheres for microencapsulation yield. However, microencapsulation efficiency increased (P < 0.05) with BO addition ranging from 36 to 61.3% for BO10 and BO30, respectively. The inclusion of BO10 in the sheep's diet did not affect the ruminal dry matter degradability (DMD) of BO over time (P > 0.05); however, BO20 and BO30 had higher (P < 0.05) DMD values than BO10. No significant differences were observed among RPF for rumen pH and temperature (P > 0.05). There was an increase (P < 0.05) in the protozoal population in the rumen environment due to the microencapsulated BO30 inclusion. There was also increase (P < 0.05) in serum albumin, cholesterol, aspartate aminotransferase (ALT), and gamma-glutamyltransferase (GGT), and a reduction (P < 0.05) in serum triglycerides of the sheep when RPF microspheres increased in the diet. Melt-emulsification proved to be a good technique for microencapsulation of buriti oil into the carnauba wax matrix. RPF from buriti oil protected into carnauba wax is recommended for sheep diet because it increases energy density, without adverse effects on the protozoal populations and blood serum metabolites from the bypass effect in the rumen.

Physicochemical Composition and Fatty Acid Profile of Goat Kids' Meat Fed Ground-Corn-Grain Silage Rehydrated with Different Additives.

The effects of the replacement of dry ground corn (GC) with corn-grain silage rehydrated with water (RCSwater), cactus pear mucilage (RCSmucilage), and whey (RCSwhey) on the growth, physicochemical composition, and fatty acid profile of goat kids' meat were investigated. Thirty-two crossbred goat kids (16.4 ± 2.50 kg initial weight) were assigned in a randomized block design with four treatments and eight repetitions. The NDF intake of goat kids fed with RCSmucilage was higher in comparison to RCSwater and RCSwhey (p = 0.0009). The dietary replacement of GC by RCSmucilage increased the final weight (p = 0.033) and meat-cooking losses (p = 0.0001) of kids. The concentrations of oleic (p = 0.046), 11,14-eicosadienoic (p = 0.033), and EPA (p = 0.010) were higher in the meat of kids fed with RCSmucilage and RCSwhey, and the α-linolenic concentration was higher (p = 0.019) for animals feeding with RCSmucilage. Meat from kids fed with RCSwhey presented the lowest ∑SFA and the highest ∑MUFA. In contrast, the ∑PUFA (p < 0.012) was higher for goats fed with RCSwater. The ∑ω3 (p < 0.0001) was higher in animals fed with RCSmucilage and RCSwhey. Desirable fatty acids were higher (p = 0.044) in animals fed with RCSmucilage and RCSwhey, and the atherogenicity (p = 0.044) and thrombogenicity (p < 0.0001) indexes were lower for goats fed the RCSwhey diet. The enzymatic activities of Δ9desaturase (C16) were higher (p = 0.027) in goat kids fed with GC and RCSmucilage, and Δ9desaturase (C18) was higher (p = 0.0497) when goats were fed with RCSmucilage and RCSwhey. Elongase activities were higher (p = 0.045) in goat kids fed with GC and RCSwater. The total replacement of GC by RCSmucilage is recommended in the diet of goat kids due to improvements in the weight gain and proportion of desirable fatty acids in the meat. In addition, RCSmucilage promoted better conservation of the silage at a lower cost when compared to commercial additives.

Modulation of Drug Resistance by Limonene: Inhibition of Efflux Pumps in Staphylococcus aureus Strains RN-4220 and IS-58.

AIMS: This study aimed to investigate the potential of limonene as an efflux pump (EP) inhibitor in Staphylococcus aureus strains, RN-4220 and IS-58, which carry EPs for erythromycin (MrsA) and tetracycline (TetK), respectively. BACKGROUND: The evolution of bacterial resistance mechanisms over time has impaired the action of most classes of antibiotics. Staphylococcus aureus is a notable bacterium, with high pathogenic potential and demonstrated resistance to conventional antibiotics. Considering the importance of discovering novel compounds to combat antibiotic resistance, our group previously demonstrated the antibacterial properties of limonene, a compound present in the essential oils of several plant species. OBJECTIVE: This study aimed to investigate the potential of limonene as an efflux pump (EP) inhibitor in Staphylococcus aureus strains RN-4220 and IS-58, which carry EPs for erythromycin (MrsA) and tetracycline (TetK), respectively. METHODS: The minimum inhibitory concentrations (MIC) of limonene and other efflux pump inhibitors were determined through the broth microdilution method. A reduction in the MIC of ethidium bromide was used as a parameter of EP inhibition. RESULT: While limonene was not shown to exhibit direct antibacterial effects against EP-carrying strains, in association with ethidium bromide and antibiotics, this compound demonstrated enhanced antibacterial activity, indicating the inhibition of the MrsA and TetK pumps. CONCLUSION: In conclusion, this pioneering study demonstrated the effectiveness of limonene as an EP inhibitor in S. aureus strains, RN-4220 and IS-58. Nevertheless, further studies are required to characterize the molecular mechanisms associated with limonene-mediated EP inhibition.

Inhibition of Efflux Pumps by Monoterpene (α-pinene) and Impact on Staphylococcus aureus Resistance to Tetracycline and Erythromycin.

INTRODUCTION: Infectious diseases have been responsible for an increasing number of deaths worldwide. Staphylococcus aureus has been recognized as one of the most notable causative agents of severe infections, while efflux pump (EP) expression is one of the main mechanisms associated with S. aureus resistance to antibiotics. OBJECTIVE: This study aimed to investigate the potential of &#945;-pinene as an efflux pump inhibitor in species of S. aureus carrying the TetK and MrsA proteins. METHODS: The minimum inhibitory concentrations (MIC) of &#945;-pinene and other efflux pump inhibitors were assessed using serial dilutions of each compound at an initial concentration above 1024 µg/mL. Solutions containing culture medium and bacterial inoculums were prepared in test tubes and subsequently transferred to 96-well microdilution plates. The modulation of ethidium bromide (EtBr) and antibiotics (tetracycline and erythromycin) was investigated through analysis of the modification in their MICs in the presence of a subinhibitory concentration of &#945;-pinene (MIC/8). Wells containing only culture medium and bacterial inoculums were used as negative control. Carbonyl cyanide m-chlorophenylhydrazone (CCCP) was used as a positive control. RESULTS: The MIC of ethidium bromide against S. aureus strains RN-4220 and IS-58 was reduced by association with α-pinene. This monoterpene potentiated the effect of tetracycline against the IS-58 strain but failed in modulating the antibacterial effect of erythromycin against RN-4220, suggesting a selective inhibitory effect on the TetK EP by &#945;- pinene. CONCLUSION: In conclusion, α-pinene has promising effects against S.aureus strains, which should be useful in the combat of antibacterial resistance associated with EP expression. Nevertheless, further research is required to fully characterize its molecular mechanism of action as an EP inhibitor.

Biological and physical approaches on the role of piplartine (piperlongumine) in cancer.

Chronic inflammation provides a favorable microenvironment for tumorigenesis, which opens opportunities for targeting cancer development and progression. Piplartine (PL) is a biologically active alkaloid from long peppers that exhibits anti-inflammatory and antitumor activity. In the present study, we investigated the physical and chemical interactions of PL with anti-inflammatory compounds and their effects on cell proliferation and migration and on the gene expression of inflammatory mediators. Molecular docking data and physicochemical analysis suggested that PL shows potential interactions with a peptide of annexin A1 (ANXA1), an endogenous anti-inflammatory mediator with therapeutic potential in cancer. Treatment of neoplastic cells with PL alone or with annexin A1 mimic peptide reduced cell proliferation and viability and modulated the expression of MCP-1 chemokine, IL-8 cytokine and genes involved in inflammatory processes. The results also suggested an inhibitory effect of PL on tubulin expression. In addition, PL apparently had no influence on cell migration and invasion at the concentration tested. Considering the role of inflammation in the context of promoting tumor initiation, the present study shows the potential of piplartine as a therapeutic immunomodulator for cancer prevention and progression.

Betulinic Acid Exerts Cytoprotective Activity on Zika Virus-Infected Neural Progenitor Cells.

Zika virus (ZIKV), a member of the Flaviviridae family, was brought into the spotlight due to its widespread and increased pathogenicity, including Guillain-Barré syndrome and microcephaly. Neural progenitor cells (NPCs), which are multipotent cells capable of differentiating into the major neural phenotypes, are very susceptible to ZIKV infection. Given the complications of ZIKV infection and potential harm to public health, effective treatment options are urgently needed. Betulinic acid (BA), an abundant terpenoid of the lupane group, displays several biological activities, including neuroprotective effects. Here we demonstrate that Sox2+ NPCs, which are highly susceptible to ZIKV when compared to their neuronal counterparts, are protected against ZIKV-induced cell death when treated with BA. Similarly, the population of Sox2+ and Casp3+ NPCs found in ZIKV-infected cerebral organoids was significantly higher in the presence of BA than in untreated controls. Moreover, well-preserved structures were found in BA-treated organoids in contrast to ZIKV-infected controls. Bioinformatics analysis indicated Akt pathway activation by BA treatment. This was confirmed by phosphorylated Akt analysis, both in BA-treated NPCs and brain organoids, as shown by immunoblotting and immunofluorescence analyses, respectively. Taken together, these data suggest a neuroprotective role of BA in ZIKV-infected NPCs.

Phytochemical analysis in Alternanthera brasiliana by LC-MS/MS and GC-MS.

Alternanthera brasiliana is popularly known as 'penicillin' and used as an anti-inflammatory and for wound healing. The objective of this work was the phytochemical study of the species by analytical techniques such as LC-MS/MS and GC-MS. Twenty-seven compounds were identified, five by LC-MS and 22 by GC-MS analysis. All compounds identified by LC-MS are flavonoids. However, several classes were found in GC-MS analysis, such as hydrocarbons, diterpenes, monoterpenes, vitamin and carotenoid derivatives, phytosterols and triterpenes. In the analysis, it is suggested the presence of 27 substances, of which 23 are unpublished for the species, that reaffirms the importance of this study and the contribution to chemical knowledge.

Inactivation of Spoilage Yeasts by Mentha spicata L. and M. × villosa Huds. Essential Oils in Cashew, Guava, Mango, and Pineapple Juices.

This study evaluated the efficacy of the essential oil from Mentha spicata L. (MSEO) and M. × villosa Huds. (MVEO) to inactivate Candida albicans, C. tropicalis, Pichia anomala and Saccharomyces cerevisiae in Sabouraud dextrose broth and cashew, guava, mango, and pineapple juices during 72 h of refrigerated storage. The effects of the incorporation of an anti-yeast effective dose of MSEO on some physicochemical and sensory characteristics of juices were evaluated. The incorporation of 3.75 µL/mL MSEO or 15 µL/mL MVEO caused a ≥5-log reductions in counts of C. albicans, P. anomala, and S. cerevisiae in Sabouraud dextrose broth. In cashew and guava juices, 1.875 µL/mL MSEO or 15 µL/mL MVEO caused ≥5-log reductions in counts of P. anomala and S. cerevisiae. In pineapple juice, 3.75 µL/mL MSEO caused ≥5-log reductions in counts of P. anomala and S. cerevisiae; 15 µL/mL MVEO caused ≥5-log reductions in counts of S. cerevisiae in mango juice. The incorporation of 1.875 µL/mL MSEO did not affect the physicochemical parameters of juices and did not induce negative impacts to cause their possible sensory rejection. These results show the potential of MSEO and MVEO, primarily MSEO, to comprise strategies to control spoilage yeasts in fruit juices.

A new coumarin derivative, 4-acetatecoumarin, with antifungal activity and association study against Aspergillus spp

Abstract Fungal infections have become a concern for health professionals, and the emergence of resistant strains has been reported for all known classes of antifungal drugs. Among the fungi causing disease, we highlight those that belong to the genus Aspergillus. For these reasons, the search for new antifungals is important. This study examines the effects of a coumarin derivative, 4-acetatecoumarin (Cou-UMB16) both alone and together with antifungal drugs, and its mode of action against Aspergillus spp. Cou-UMB16 was tested to evaluate its effects on mycelia growth, and germination of Aspergillus spp. fungal conidia. We investigated its possible action on cell walls, on the cell membrane, and also the capacity of this coumarin derivative to enhance the activity of antifungal drugs. Our results suggest that Cou-UMB16 inhibits Aspergillus spp. virulence factors (mycelia growth and germination of conidia) and affects the structure of the fungal cell wall. When applying Cou-UMB16 in combination with azoles, both synergistic and additive effects were observed. This study concludes that Cou-UMB16 inhibits mycelial growth and spore germination, and that the activity is due to its action on the fungal cell wall, and that Cou-UMB16 could act as an antifungal modifier.

Artificial intelligence on the identification of risk groups for osteoporosis, a general review.

INTRODUCTION: The goal of this paper is to present a critical review on the main systems that use artificial intelligence to identify groups at risk for osteoporosis or fractures. The systems considered for this study were those that fulfilled the following requirements: range of coverage in diagnosis, low cost and capability to identify more significant somatic factors. METHODS: A bibliographic research was done in the databases, PubMed, IEEExplorer Latin American and Caribbean Center on Health Sciences Information (LILACS), Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, Web of Science, and Science Direct searching the terms "Neural Network", "Osteoporosis Machine Learning" and "Osteoporosis Neural Network". Studies with titles not directly related to the research topic and older data that reported repeated strategies were excluded. The search was carried out with the descriptors in German, Spanish, French, Italian, Mandarin, Portuguese and English; but only studies written in English were found to meet the established criteria. Articles covering the period 2000-2017 were selected; however, articles prior to this period with great relevance were included in this study. DISCUSSION: Based on the collected research, it was identified that there are several methods in the use of artificial intelligence to help the screening of risk groups of osteoporosis or fractures. However, such systems were limited to a specific ethnic group, gender or age. For future research, new challenges are presented. CONCLUSIONS: It is necessary to develop research with the unification of different databases and grouping of the various attributes and clinical factors, in order to reach a greater comprehensiveness in the identification of risk groups of osteoporosis. For this purpose, the use of any predictive tool should be performed in different populations with greater participation of male patients and inclusion of a larger age range for the ones involved. The biggest challenge is to deal with all the data complexity generated by this unification, developing evidence-based standards for the evaluation of the most significant risk factors.

Warifteine, an alkaloid of Cissampelos sympodialis, modulates allergic profile in a chronic allergic rhinitis model

ABSTRACT Cissampelos sympodialis Eichler, Menispermaceae, a Brazilian medicinal plant and its alkaloid warifteine present immunomodulatory activity on asthma experimental model by reducing antigen-specific IgE levels, eosinophil infiltration and lung hyperactivity. Allergic rhinitis is a chronic inflammatory disorder of the nasal tissue that affect the quality of life and it is a risk factor for asthma exacerbation. This study evaluated the effect of inhaled warifteine in an allergic ovalbumin rhinitis model. Inhaled warifteine (2 mg/ml) treatment of ovalbumin-sensitized BALB/c mice significant decreased total and differential number of cells on the nasal cavity and decreased ovalbumin-specific IgE serum levels. Hematoxylin & eosin staining of histological preparations of ovalbumin nasal tissues showed changes such as congestion and a massive cell infiltration in the perivascular and subepithelial regions characterizing the nasal inflammatory process. However, inhaled warifteine or dexamethasone treatment decreased cell infiltration into the perivascular regions and it was observed an intact nasal tissue. Periodic acidic staining of nasal epithelium of ovalbumin animals demonstrated high amount of mucus production by goblet cells and inhaled warifteine or dexamethasone treatment modulated the mucus production. In addition, toluidine blue staining of the nasal epithelium of ovalbumin animals demonstrated an increase of mast cells on the tissue and inhaled warifteine or dexamethasone treatment decreased in average of 1.4 times the number of these cells on the nasal epithelium. Taken these data together we postulate that warifteine, an immunomodulatory alkaloid, can be a medicinal molecule prototype to ameliorate the allergic rhinitis conditions.

A new coumarin derivative, 4-acetatecoumarin, with antifungal activity and association study against Aspergillus spp.

Fungal infections have become a concern for health professionals, and the emergence of resistant strains has been reported for all known classes of antifungal drugs. Among the fungi causing disease, we highlight those that belong to the genus Aspergillus. For these reasons, the search for new antifungals is important. This study examines the effects of a coumarin derivative, 4-acetatecoumarin (Cou-UMB16) both alone and together with antifungal drugs, and its mode of action against Aspergillus spp. Cou-UMB16 was tested to evaluate its effects on mycelia growth, and germination of Aspergillus spp. fungal conidia. We investigated its possible action on cell walls, on the cell membrane, and also the capacity of this coumarin derivative to enhance the activity of antifungal drugs. Our results suggest that Cou-UMB16 inhibits Aspergillus spp. virulence factors (mycelia growth and germination of conidia) and affects the structure of the fungal cell wall. When applying Cou-UMB16 in combination with azoles, both synergistic and additive effects were observed. This study concludes that Cou-UMB16 inhibits mycelial growth and spore germination, and that the activity is due to its action on the fungal cell wall, and that Cou-UMB16 could act as an antifungal modifier.

Chemical composition and antibacterial activity of essential oil from leaves of Croton heliotropiifolius in different seasons of the year

ABSTRACT This paper reports the first study of the variation of the chemical composition and abundance of the essential oil of Croton heliotropiifolius, in four seasons, and the evaluation of its antibacterial activity. Essential oil obtained from leaves of C. heliotropiifolius were analyzed by GC/MS and evaluated against eight bacteria strains by broth microdilution method. The chemical constituents identified were the same in all samples, but with different proportions. The total percentages identified were 96.58% in summer, 92.08% in autumn, 98.44% in winter and 90.78% in spring. The majors constituents are β-caryophyllene, bicyclogermacrene, germacrene-D, limonene and 1,8-cineole. β-Caryophyllene was the major compound in all samples. The results of the antibacterial evaluations showed weak to moderate activity against the analyzed strains. In all analyzes was observed that essential oil sample collected in summer stands out from the others, displaying stronger activity against Gram-positive as Gram-negative bacteria.

Antispasmodic activity from Serjania caracasana fractions and their safety

Abstract In a previous study, we reported the antispasmodic and gastroprotective effects of the Serjania caracasana (Jacq.) Willd., Sapindaceae, extract. In the present study, we evaluated the LD50, hemolytic and antispasmodic activities of its fractions and characterized its major constituents by isolation and GC-MS. The animals showed non-toxic symptoms with oral doses up to 2000 mg/kg, suggesting a safe oral administration. Furthermore, a low hemolytic activity was detected for the saponin fraction. Antispasmodic activity of the fractions was evaluated through carbachol-induced contractions in rat ileum. The hexane fraction was the most potent (IC50 68.4 ± 5.9 µg/ml) followed by the dichloromethane fraction (IC50 161.3.4 ± 40.7 µg/ml). Butanol fraction was the less effective (IC50 219.8 ± 60.3 µg/ml). The phytochemical study of the S. caracasana fractions afforded the isolation of friedelin, β-amyrin, allantoin and quercitrin. This is the first time that the presence of allantoin and quercitrin in the Serjania genus has been reported. Among the isolated compounds and those characterized by GC-MS, β-amyrin and β-sitosterol were present in the most active fractions, hexane and dichloromethane, and they may be related to its antispasmodic activity. In addition, spathulenol was only found in the hexane fraction and its presence might justify the highest antispasmodic activity observed for this fraction.

In silico and In vivo Toxicological Evaluation of Cissampelos Sympodialis Secondary Metabolites in Rattus Norvegicus.

Cissampelos sympodialis is a plant in northeastern Brazil used by the populace for treating respiratory diseases. Several studies have shown that ethanol leaf extracts have immunomodulatory and anti-inflammatory activities. Infusions are widely used, popular, and an ancient technique in traditional medicine, using hot water alone as the means of extraction. This study aimed to investigate acute toxicological potential of leaf infusions of Cissampelos sympodialis, when applied orally at a dose of 2000mg/kg to Rattus norvegicus, combined with an in silico study of 117 alkaloids present in the Cissampelos genus; five (5) of which were determined to have high toxicity (21, 8, 93, 32 and 88), and five (5) having both low toxicity (57, 77, 28, 25 and 67) and low liver metabolism. The in vivo toxicological evaluation showed that male water consumption decreased, and the feed intake decreased in both sexes. Yet, the figures as to change in weight gain of the animals were not statistically sufficient. As for the biochemical parameters, there was an increase in urea, and decreases in uric acid and AST in males. In females, there was a decrease in albumin and globulin which consequently leads to a total protein decrease. Despite biochemical changes suggestive of kidney damage, the histological sections revealed no kidney or liver changes. The results therefore indicate that despite presenting alkaloids which may be toxic, the genus Cissampelos, or leaf infusions of Cissampelos sympodialis, when applied orally at a dose of 2000mg/kg present low toxicity.

Docking Studies for Multi-Target Drugs.

The most basic principle of drug action is found in the lock and key model, where the highest possible affinity for a target that also avoids side effects is desired. For many years this was understood as being "one drug, for one target, for one disease", however researchers began to observe that certain diseases are best treated with multi-target drugs. In recent years, studies have sought out polypharmacological compounds acting on multiple targets against complex (multifactorial) diseases, such as cancer, neurodegenerative disease, and certain infections. One of the computational tools used in research for multifunctional drugs is Molecular Docking. Through this methodology of Computer-Aided Drug Design, we observe complexes formed between ligands and interesting targets (often many), for a particular disease. This review reports on docking studies as used in investigations of new multi-target compounds; it also shows the various ways that such studies are used in the search for multifunctional compounds.

Secondary Metabolites from Cissampelos, A Possible Source for New Leads with Anti-Inflammatory Activity.

The genus Cissampelos comprises of 21 species which have a wide global distribution and various pharmacological activities such as analgesic and antipyretic, antiinflammatory, anti-allergic, bronchodilation, and immunomodulation among others. Several compounds, mainly alkaloids with differing biological activities have been isolated from this genus. We will highlight antipyretic activities, anti-inflammatory, antiallergic, bronchodilatory, and immunomodulatory activities. In addition, we applied ligand-based-virtual screening associated with structure-based-virtual screening of a small dataset of 63 secondary metabolites from the Cissampelos genus of an in-house data bank, in order to select compounds with potential anti-inflammatory activity. Affinities were observed for hayatine (26), isochondrondendrine (30), pelosine (52), sepeerine (59), and warifteine (63) to the inhibiting enzymes MAPK p38 alpha, PKC beta, PKC theta and PKC zeta. The cissampeloflavone compound (8) alone showed no potential inhibitory activity for PKC zeta, or affinity for the PKC alpha. The compounds can be used as starting points for further studies on structures with potential anti-inflammatory activity.

Ortho-eugenol exhibits anti-nociceptive and anti-inflammatory activities.

Ortho-eugenol is a much used phenylpropanoid whose ability to reduce pain and inflammation has never been studied. Researching ortho-eugenol's antinociceptive and anti-inflammatory activity, and its possible mechanisms of action is therefore of interest. The administration of vehicle, ortho-eugenol (50, 75 and 100mg/kg i.p.), morphine (6mg/kg, i.p.) or dexamethasone (2mg/kg, s.c.) occurred 30min before the completion of pharmacological tests. Pretreatment with ortho-eugenol did not change motor coordination test results, but reduced the number of writhes and licking times in the writhing test and glutamate test, respectively. The reaction time from thermal stimulus was significantly increased in the hot plate test after administration of ortho-eugenol. Treatment with yohimbine reversed the antinociceptive effect of ortho-eugenol, suggesting involvement of the adrenergic system. In anti-inflammatory tests, ortho-eugenol inhibited acetic acid induced vascular permeability and leukocyte migration, reducing TNF-α and IL-1ß by virtue of its suppression of NF-κB and p38 phosphorylated forms in the peritonitis test. From these results, ortho-eugenol antinociceptive effects mediated by the adrenergic system and anti-inflammatory activity through regulation of proinflammatory cytokines and phosphorylation of NF-kB and p38 become evident for the first time.

Multi-Target Drugs for Neglected Diseases.

BACKGROUND: Diseases perceived as neglected tropical infections are generally caused by parasites which reach poor, underserved populations (primarily infrastructure), cause serious damage to health, and many deaths. AIDS and tuberculosis, (although not classified as neglected by WHO), are discriminated against infections which cause great social damage. The drugs currently used to treat these diseases do not have the desired effectiveness, enable the emergence of resistant strains, and in most cases are difficult to obtain. Few pharmaceutical companies are investing in new drug research for neglected diseases, for lack of financial return. This review reports the major neglected diseases, AIDS, tuberculosis, their targets, and research on multi-target drugs. METHODS: The studies for new drugs against these infections involve in silico methods, synthesis, structural determinations, analytical analysis and other experimental assays. RESULTS: A new single compound, forecasting possible pharmacodynamic and pharmacokinetic interactions becomes a simpler process; it is also believed that these drugs are safer and more efficient, since they act with synergism on different targets. It occurs but the emergence of new resistant strains and side effects. CONCLUSION: Multi-target drugs represent a new alternative to find new lead compounds. A ligand that targets two or more receivers may be seen as a potential drug, combating infection by different routes.