Chemical Profile and Biological Activities Of Piper mikanianum (Kunth) Steud Essential Oil for Development and Improvement of Oral Rinse.

INTRODUCTION: Studies prove that the use of medicinal plants is a custom carried out by man since ancient times, the evolution of the pharmaceutical industry makes more people consume more natural products. Currently, we can observe that mouthwashes containing natural compounds have shown a growth in demand in the markets and in the professional community. OBJECTIVE: The present study aims to carry out the chemical characterization and microbiological potential of Piper mikanianum (Kunth) Steud essential oil (EOPm), providing data that allows the development of a low-cost mouthwash formulation aimed at vulnerable communities. METHODS: The evaluation of the antibacterial activity and modulator of bacterial resistance was performed by the microdilution method to determine the minimum inhibitory concentration (MIC). The chemical components were characterized by gas chromatography coupled to mass spectrometry, identified 28 constituents, in which Safrole Phenylpropanoid is the major compound, representing 72.6 % of the total composition, followed by α-pinene (10.7 %), Limonene (2 %), ß-caryophyllene (2 %), E-nerolidol (1.9 %), spathulenol (1.3 %) and camphene (1.1 %). RESULTS: The EOPm showed a MIC minimum inhibitory concentration≥1024 µg/mL for all bacterial strains used in the tests. When the EOPm modulating activity combined with chlorhexidine, mouthwash, ampicillin, gentamicin and penicillin G was evaluated against bacterial resistance, the oil showed significant synergistic activity, reducing the MIC of the products tested in combination, in percentage between 20.6 % to 98 .4 %. CONCLUSIONS: We recommend the expansion of tests with greater variation of EOPm concentration combinations and the products used in this study, as well as toxicity evaluation and in vivo tests, seeking the development of a possible low-cost mouthwash formulation accessible to the most vulnerable population.

Anti-diarrheal effect of piperine possibly through the interaction with inflammation inducing enzymes: In vivo and in silico studies.

Piperine is a natural alkaloid that possesses a variety of therapeutic properties, including anti-inflammatory, antioxidant, antibacterial, and anticarcinogenic activities. The present study aims to assess the medicinal benefits of piperine as an anti-diarrheal agent in a chick model by utilizing in vivo and in silico techniques. For this, castor oil was administered orally to 2-day-old chicks to cause diarrhea. Bismuth subsalicylate (10 mg/kg), loperamide (3 mg/kg), and nifedipine (2.5 mg/kg) were used as positive controls, while the vehicle was utilized as a negative control. Two different doses (25 and 50 mg/kg b.w.) of the test sample (piperine) were administered orally, and the highest dose was tested with standards to investigate the synergistic activity of the test sample. In our findings, piperine prolonged the latent period while reducing the number of diarrheal feces in the experimental chicks during the monitoring period (4 h). At higher doses, piperine appears to reduce diarrheal secretion while increasing latency in chicks. Throughout the combined pharmacotherapy, piperine outperformed bismuth subsalicylate and nifedipine in terms of anti-diarrheal effects with loperamide. In molecular docking, piperine exhibited higher binding affinities towards different inflammatory enzymes such as cyclooxygenase 1 (-7.9 kcal/mol), cyclooxygenase 2 (-8.4 kcal/mol), nitric oxide synthases (-8.9 kcal/mol), and L-type calcium channel (-8.8 kcal/mol), indicating better interaction of PP with these proteins. In conclusion, piperine showed a potent anti-diarrheal effect in castor oil-induced diarrheal chicks by suppressing the inflammation and calcium ion influx induced by castor oil.

Evaluation of the antibacterial activity of hecogenin acetate and its inhibitory potential of NorA and MepA efflux pumps from Staphylococcus aureus.

Antimicrobial drugs are of great importance in the control of bacterial infections. Its indiscriminate use contributes to the consolidation of bacterial resistance. Its applicability is due to its secondary metabolites, such as saponins, which are compounds with relevant antibacterial action. Hecogenin acetate is a saponin present in plants of the agave genus with analgesic, antioxidant, antinociceptive, cardioactive, anticancer, antifungal and antimicrobial activity. The present work aimed to identify the antibacterial activity of hecogenin acetate against strains of E. coli, P. aeruginosa and S. aureus and to investigate the NorA and MepA efflux pump inhibitory activity of S. aureus strains. The Minimum Inhibitory Concentration was evaluated by broth microdilution. The Antibiotic Activity Modifier effect and the assessment of efflux pump inhibition were evaluated by microdilution with sub-inhibitory concentrations. Hecogenin acetate showed minimal inhibitory concentration without significant relevance. In the evaluation of the potentiating activity of the antibiotic action, a greater antagonistic behavior is noticed. In the analyzes performed with the efflux pump, it was noticed that the hecogenin acetate does not interfere in the efflux pump mechanism of the analyzed bacteria.

Herb and Spices in Colorectal Cancer Prevention and Treatment: A Narrative Review.

Colorectal cancer (CRC) is the second most deadly cancer worldwide. CRC management is challenging due to late detection, high recurrence rate, and multi-drug resistance. Herbs and spices used in cooking, practised for generations, have been shown to contain CRC protective effect or even be useful as an anti-CRC adjuvant therapy when used in high doses. Herbs and spices contain many bioactive compounds and possess many beneficial health effects. The chemopreventive properties of these herbs and spices are mainly mediated by the BCL-2, K-ras, and MMP pathways, caspase activation, the extrinsic apoptotic pathway, and the regulation of ER-stress-induced apoptosis. As a safer natural alternative, these herbs and spices could be good candidates for chemopreventive or chemotherapeutic agents for CRC management because of their antiproliferative action on colorectal carcinoma cells and inhibitory activity on angiogenesis. Therefore, in this narrative review, six different spices and herbs: ginger (Zingiber officinale Roscoe), turmeric (Curcuma longa L.), garlic (Allium sativum L.), fenugreek (Trigonella foenum-graecum L.), sesame (Sesamum indicum L.), and flaxseed (Linum usitatissimum L.) used in daily cuisine were selected for this study and analyzed for their chemoprotective or chemotherapeutic roles in CRC management with underlying molecular mechanisms of actions. Initially, this study comprehensively discussed the molecular basis of CRC development, followed by culinary and traditional uses, current scientific research, and publications of selected herbs and spices on cancers. Lead compounds have been discussed comprehensively for each herb and spice, including anti-CRC phytoconstituents, antioxidant activities, anti-inflammatory properties, and finally, anti-CRC effects with treatment mechanisms. Future possible works have been suggested where applicable.

Bioactive Compounds as Potential Agents for Sexually Transmitted Diseases Management: A Review to Explore Molecular Mechanisms of Action.

Sexually transmitted diseases (STDs) are produced by pathogens like bacteria, fungi, parasites, and viruses, and may generate severe health problems such as cancer, ulcers, and even problems in the newborn. This narrative review aims to present updated information about the use of natural bioactive compounds for the prevention and treatment of sexually transmitted infections. A search of the literature was performed using databases and search engines such as PubMed, Scopus, Google Scholar and Science Direct. From the pharmacotherapeutic management point of view, any strategies for prevention should contain medical approaches. The bioactive compounds obtained from natural products have shown biological effects against different microorganisms for the treatment of these diseases. The main results showed antimicrobial, antiprotozoal, antifungal and antiviral effects such as HIV. Also, the molecular mechanisms, signalling pathways and action targets of natural compounds were highlighted, thus justifying bacterial and antifungal inhibition, apoptosis or reduction of viral replication. From the data of our study, we can conclude that natural compounds may be a significant source for adjuvant drugs / complementary therapies in the treatment of STDs. With all these benefits, the future must conduct extensive clinical trials and the development of pharmaceutical nanotechnologies for a greater therapeutic effect.

Characterization of ß-cyclodextrin/myrtenol complex and its protective effect against nociceptive behavior and cognitive impairment in a chronic musculoskeletal pain model.

Myrtenol has gained wide interest because of its pharmacological profiles, mainly for treatment of chronic diseases. To improve the solubility of myrtenol, the formation of inclusion complexes with ß-cyclodextrin was performed by physical mixture, kneading process or slurry complexation (SC) methods and characterized using thermal analysis, XRD, SEM and NMR. From these results, myrtenol complexed by SC was successfully complexed into ß-cyclodextrin cavity. The interaction between myrtenol and ß-cyclodextrin was confirmed by molecular docking. Hence, the SC ß-cyclodextrin-myrtenol complex was evaluate for its anti-hyperalgesic, anxiolytic and antioxidant activity in a fibromyalgia model. Results show that myrtenol and ß-cyclodextrin form a stable complex and have anti-hyperalgesic effect, improve the cognitive impairment caused and have an anxiolytic-like effect. Furthermore, the ß-cyclodextrin/myrtenol complex decrease lipoperoxidation, increased catalase activity and a reduce SOD/CAT ratio. Therefore, ß-cyclodextrin/myrtenol complex reduce painful behavior, improves motor skills and emotional behavior and decreases oxidative stress in a fibromyalgia model.

Antiedematogenic and Anti-Inflammatory Activity of the Monoterpene Isopulegol and Its ß-Cyclodextrin (ß-CD) Inclusion Complex in Animal Inflammation Models.

Isopulegol (ISO) is an alcoholic monoterpene widely found in different plant species, such as Melissa officinalis, and has already been reported to have a number of pharmacological properties. Like other terpenes, ISO is a highly volatile compound that is slightly soluble in water, so its inclusion into cyclodextrins (CDs) is an interesting approach to increase its solubility and bioavailability. Thus, our aim was to evaluate the antiedematogenic and anti-inflammatory activity of isopulegol and a ß-cyclodextrin-isopulegol inclusion complex (ISO/ß-CD) in rodent models. For the anti-inflammatory activity evaluation, antiedematogenic plethysmometry and acute (peritonitis and pleurisy), as well as chronic (cotton pellet-induced granuloma) anti-inflammatory models, were used. The docking procedure is used to evaluate, analyze, and predict their binding mode of interaction with H1 and Cox-2 receptors. The animals (n = 6) were divided into groups: ISO and ISO/ß-CD, negative control (saline), and positive control (indomethacin and promethazine). ISO and ISO/ß-CD were able to reduce acute inflammatory activity by decreasing albumin extravasation, leukocyte migration, and MPO concentration, and reducing exudate levels of IL-1ß and TNF-α. ISO and ISO/ß-CD significantly inhibited edematogenic activity in carrageenan- and dextran-induced paw edema. Moreover, both significantly reduced chronic inflammatory processes, given the lower weight and protein concentration of granulomas in the foreign body granulomatous inflammation model. The results suggest that the inclusion of ISO in ß-cyclodextrins improves its pharmacological properties, with the histamine and prostaglandin pathways as probable mechanisms of inhibition, and also reinforces the anti-inflammatory profile of this terpene.

Myorelaxant action of the Dysphania ambrosioides (L.) Mosyakin & Clemants essential oil and its major constituent α-terpinene in isolated rat trachea.

This study aimed to investigate the myorelaxant action of the Dysphania ambrosioides essential oil (EODa) and its major constituent α-terpinene on tracheal smooth muscle isolated from rats. In tracheal smooth muscle ex vivo, in organ baths, isometric contractions recordings were done in order to evaluated the effect of EODa (1-1000 µg/mL) and α-terpinene (1-3000 µg/mL) on the following parameters: basal tone, contractions evoked by potassium (KCl 60 mM), acetylcholine (ACh 10 µM) or serotonin (5-HT 10 µM). The EODa and its major constituent α-terpinene, did not statistically alter basal tone; however, they induced myorelaxant effects on top of contractions induced by KCl, ACh and 5-HT. EODa and α-terpinene also inhibited the contractions induced by barium in presence of High [K+] (80 mM). The data suggest that the relaxation induced by these agents is caused by the inhibition of L-type VGCC, inhibiting the inward Ca2+ current through these channels, but does not exclude the possibility of participation of other mechanisms. Results from this study also suggest the EODa, due to their efficacy on relaxation of the respiratory tract, posses a therapeutic potential as a antispasmodic agent for respiratory tract.

GC/MS analysis and antimicrobial activity of the Piper mikanianum (Kunth) Steud. essential oil.

The Piper mikanianum species were investigated by the antimicrobial potential and chemical composition. Chemical analysis was performed by gas chromatography coupled to mass spectrometry (GC/MS). The Minimum Inhibitory Concentration (MIC) as well as the 50% Inhibitory Concentration against Candida strains were determined by microdilution. The effect of the drug-oil combination was also evaluated to verify possible synergism. The Minimum Fungicidal Concentration (MFC) was evaluated by subculturing the microdilution in Petri dishes and the anti-pleomorphism potential of the oil was tested in humid chambers. Chemical analysis revealed safrol as the major compound. The results from the intrinsic activity evaluation of the oil did not reveal a clinical importance, however, it presented a synergistic effect when associated with gentamicin against the multidrug resistant E. coli strain and when associated with fluconazole against fungal strains. Moreover, the oil possessed a fungistatic effect. Total inhibition of filamentous structures occurred in both Candida species in the anti-virulence test. The P. mikanianum essential oil showed a potentiating activity of drugs for which resistance exists and an inhibitory effect of one of the main virulence factors of the Candida genus, morphological transition, which has been previously shown to be responsible for causing invasive infections in human tissues.

GC-MS-FID characterization and antibacterial activity of the Mikania cordifolia essential oil and limonene against MDR strains.

The present study evaluated the effect of the essential oil of Mikania cordifolia (EOMc) and its major constituent limonene alone or associated with antibacterial drugs against Multidrug Resistant Bacteria (MDR). To evaluate the antibacterial activity, the minimum inhibitory concentrations (MIC) of the oil and limonene against Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus were determined. The antibiotic-modulating activity was assessed using subinhibitory concentrations (MIC/8) of these substances in combination with conventional antibacterial drugs. Although no relevant antibacterial activity of the natural products was detected, both substances modulated the action of antibiotics against resistant bacteria. The EOMc demonstrated the best modulating effect against P. aeruginosa, presenting synergistic effects when associated with gentamicin and norfloxacin. In addition, the oil reduced the MIC of norfloxacin against E. coli as well as reduced the MIC of gentamicin against S. aureus. On the other hand, the best effect of limonene was obtained against S. aureus. Thus, it is concluded that the essential oil Mikania cordifolia and the isolated compound limonene do not have clinically significant antibacterial effect, but modulate the action of antibiotics against MDR bacteria.

Chemical composition, antimicrobial, modulator and antioxidant activity of essential oil of Dysphania ambrosioides (L.) Mosyakin & Clemants.

The oil presented the α-Terpinene as the major compound with 54.09% presence. Antibacterial activity demonstrated significant MIC against Staphylococcus aureus (256 µg/mL) and moderate against Pseudomonas aeruginosa (512 µg/mL). The modulating effect of antibiotics was significant against P. aeruginosa potentiating the effect of all the antibiotics tested. The IC50 observed for CT LM 23 was clinically relevant (19.3 µg/mL), similar to that obtained for CA INCQS 40006 (25.2 µg/mL). The combined effect with fluconazole also showed significant results, 0.1 and 22.7 µg/mL, for CT LM 23 and CA INCQS 40006, respectively. For CA LM 77 the IC50 was 101.9 µg/mL and for CT INCQS 40042 a value of 53.3 µg/mL. Regarding the modulation, both were considered of clinical relevance, 3.3 and 6.4 µg/mL. OEDA has low antioxidant activity (>1024 µg/mL). Therefore, the popular use against infections was corroborated by this work.

Toxicological and pharmacologic effects of farnesol (C15H26O): A descriptive systematic review.

The objective of the present study was to perform a systematic review (SR) composed of preclinical and clinical studies which investigated the toxicological and pharmacologic effects of farnesol [Molecular formula: C15H26O; IUPAC: (3,7,11-Trimethyl-2,6,10-dodecatrien-1-ol]. This SR was performed according to PRISMA guidelines. Literature research was performed using PubMed, MEDLINE, Scopus and Web of Science databases using the descriptor combinations: "farnesol and pharmacological effect" and "farnesol and toxicology". The inclusion criteria used were original articles from preclinical and clinical studies investigating the pharmacological and toxicological effects of farnesol, published between January 1960 and December 2017 which were written in English, Portuguese and Spanish. Primary research identified 414 articles, from which 76 articles were selected for final analysis following the inclusion criteria. After grouping, 51.32 and 22.37% of the articles investigated the antimicrobial and antitumor effect, respectively. Methodological biases have been observed both in pre-clinical studies with non-human animals and in clinical trials, mainly in group allocation and blinding. This SR is the first study developed to compile the studies concerning the pharmacological and toxicological effects of farnesol. This study concludes that farnesol possesses different pharmacological and toxicological features, which permit its use as an active or a coadjuvant drug.

GC-MS analysis of the fixed oil from Sus scrofa domesticus Linneaus (1758) and antimicrobial activity against bacteria with veterinary interest.

The bioprospection of zootherapeutic products can be a source of new drugs and to the creation of new strategies of natural resources conservation and management of endangered species. This fact is supported by ethnobiological studies indicating that the usage of zootherapeutic products can be replaced by the use of natural products isolated from plants and domestic animals. The emergence of antibiotic-resistant bacteria has increased the need for research for new active principles. Ethnoveterinary studies in Brazil have shown that Sus scrofa domesticus fat is used for diseases associated with bacterial pathogens. The objective of this study was to identify the chemical composition and to evaluate the antibacterial activity of the fixed oil of Sus scrofa domesticus (OFSC) when used alone or associated with antibiotics. In the analysis of the oil composition, there were 4 constituents identified, with oleic acid being the major constituent. The OFSC did not present antibacterial activity when tested alone; however, it showed synergism in the modulating activity when associated with antibiotics Amikacin and Amoxicillin.

Antiparasitic Activity and Essential Oil Chemical Analysis of the Piper Tuberculatum Jacq Fruit.

With the increase of neglected diseases such as leishmaniasis and Chagas disease, there was a need for the search for new therapeutic alternatives that reduce the harm caused by medicine available for treatment. Thus, this study was performed to investigate the antiparasitic activity of the essential oil from the fruits of Piper tuberculatum Jacq, against lines of Leishmania braziliensis (MHOM/CO/88/UA301), Leishmania infantum (MHOM/ES/92/BCN83) and Trypanosoma cruzi (LC-B5 clone). Before running protocols, an analysis of the chemical composition of essential oil was conducted, which presented monoterpenes and sesquiterpenes. As major constituents, ß-pinene and α-pinene were identified. Regarding to antiparasitic activity, the essential oil had an EC50 values of 133.97 µg/mL and 143.59 µg/mL against variations promastigotes of L. infantum and L. braziliensis, respectively. As for trypanocidal activity, the oil showed EC50 value of 140.31 µg/mL against epimastigote form of T. cruzi. Moreover, it showed moderate cytotoxicity in fibroblasts with LC50 value of 204.71 µg/mL. The observed effect may be related to the presence of terpenes contained in the essential oil, since it has its antiparasitic activity proven in the literature.

Antitrypanosomal, antileishmanial and cytotoxic activities of Brazilian red propolis and plant resin of Dalbergia ecastaphyllum (L) Taub.

The treatment for leishmaniasis and Chagas disease can be hard and painful, such that many patients give up on the treatment. In order to find an alternative path for the treatment of these diseases, researchers are using natural products to fight these parasites. The aim of this study was to evaluate the antiprotozoan and cytotoxic activities of red propolis samples collected from different Brazilian states and seasons whilst searching for possible activity differences. We also compared the red propolis results with the ones obtained for the plant resin extract collected from Dalbergia ecastaphyllum trees. The hydroethanolic red propolis extracts from Pernambuco and Alagoas, and the D. ecastaphyllum resin were evaluated regarding their antileishmanial, antitrypanosomal and cytotoxic activity. All extracts showed antiprotozoan and cytotoxic activity. RP-PER showed to be more cytotoxic against protozoan parasites and fibroblast cells. All propolis extracts showed a higher cytotoxic activity when compared to resin extracts. The propolis sample collected in Pernambuco during the rainy season killed the parasites with lower concentrations than the sample collected in the dry season. The IC50 observed against the parasites could be used without high fibroblast cell damage.

Avaliação da atividade moduladora e citotóxica do óleo essencial das folhas de Hyptis martiusii Benth / Evaluación de la actividad moduladora y citotóxica del aceite esencial de las hojas de Hyptis martiusii Benth / Assessment of Modulatory and Cytotoxic Activity of the Essential Oil in Hyptis Martiusii Benth Leaves

Resumo Introdução: a espécie Hyptis martiusii Benth, comumente chamada de "cidrera del campo", têm múltiplas propriedades biológicas, como ser inseticida, antifúngica e anti-inflamatória. O objetivo deste estudo foi investigar a atividade moduladora do óleo essencial das folhas frescas de Hyptis martiusii em associação com diferentes antibióticos contra as bactérias Staphylococcus aureus, Escherichia coli e Pseudomonas aeruginosa, e avaliar a atividade citotóxica da espécie. Materiais e métodos: o estudo utilizou a concentração inibitória mínima (CIM) como uma forma de avaliar a modulação com uma inoculação de 100 microlitros de cada estirpe bacteriana. As provas de citotoxicidade se realizaram mediante cultivo in vitro de células do tecido conectivo de camundongo (fibroblastos de mamíferos). Resultados: a pesquisa demonstrou que o óleo essencial das folhas de Hyptis martiusii Benth (OEHM) apresenta sinergismo só em associação com os antibióticos gentamicina e imipenem contra as bactérias Pseudomonas aeruginosa e Escherichia coli. No entanto, apresenta antagonismo em associação com amicacina, gentamicina e imipenem contra as três bactérias estudadas. Para além da ciprofloxacina não demonstrou resultados relevantes. Em relação com a atividade citotóxica, a concentração letal média (LC50) expôs um valor de 263,12 [ig/ml. Conclusão: finalmente, revelou-se que a H. martiusii apresenta atividade citotóxica sinérgica contra as bactérias avaliadas.

Resumen Introducción: la especie Hyptis martiusii Benth, comúnmente llamada "cidreira do campo", tiene múltiples propiedades biológicas, como ser insecticida, antifúngica y antiinflamatoria. El objetivo de este estudio fue investigar la actividad moduladora del aceite esencial de las hojas frescas de Hyptis martiusii en asociación con diferentes antibióticos contra las bacterias Staphylococcus aureus, Escherichia coli y Pseudomonas aeruginosa, y evaluar la actividad citotóxica de la especie. Materiales y métodos: el estudio utilizó la concentración mínima inhibitoria (CMI) como una forma de evaluar la modulación con una inoculación de 100 microlitros de cada cepa bacteriana. Las pruebas de citotoxicidad se realizaron mediante cultivo in vitro de células de tejido conectivo de ratón (fibroblastos de mamíferos). Resultados: la investigación demostró que el aceite esencial de las hojas de Hyptis martiusii Benth (OEHM) presenta sinergismo solo en asociación con los antibióticos gentamicina e imipenem contra las bacterias Pseudomonas aeruginosa y Escherichia coli. Sin embargo, presenta antagonismo en asociación con amikacina, gentamicina e imipenem contra las tres bacterias estudiadas. Además de la ciprofloxacina, no demostró resultados relevantes. En relación con la actividad citotóxica, la concentración letal media (CL50) exhibió un valor de 263,12 [ig/ml. Conclusión: finalmente, se reveló que la H. martiusii presenta actividad citotóxica sinérgica contra las bacterias evaluadas.

Abstract Introduction: The species Hyptis martiusii Benth. commonly called "cidreira do campo" has multiple biological properties, such as antifungal, anti-inflammatory, and insecticide. The aim of this study was to investigate the modulating activity of the essential oil of the fresh leaves of Hyptis martiusii in association with different antibiotics against the bacteria Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, as also the cytotoxic activity of this species. Materials and methods: The study used the MIC (minimum inhibitory concentration) as a way of assessing the modulation using an inoculation of 100 microliters of each bacterial strain. The cytotoxicity tests were conducted using in vitro culture of mouse connective tissue cells (fibroblasts of mammals). Results: The research demonstrated that the essential oil from leaves of Hyptis martiusii Benth (OEHM) presented synergism only when associated with the antibiotics gentamicin and imipenem against the bacteria Pseudomonas aeruginosa and Escherichia coli. However, it presented antagonism in association with amikacin, gentamicin and imipenem against the three studied bacteria. In addition to the ciprofloxacin showed no relevant results. In relation to the cytotoxic activity the lethal concentration (LC50) exhibited a value of 263.12 [ig/ml. Conclusion: Ultimately it was established, that H. Martiusii presents a synergistic cytotoxic activity against the evaluated bacteria.

Evaluation of the antioxidant and gastroprotective activity and HPLC analysis of the hydroalcoholic extract of Tocoyena formosa leaves (Cham. & Schlecht) K. Schum.

The peptic ulcer is a gastric disorder that affects millions of people and yet they cause many side effects. In this sense, natural products represent an important alternative to the discovery of compounds with gastroprotective activity. The present work has as its objective to evaluate the antioxidant and gastroprotective activity of the Hydroalcoholic Extract of Leaves from Tocoyena formosa (Cham. & Schlecht.) K. Schum (HELTF), this being much emphasized in traditional medicine for inflammatory morbidities and gastric symptoms. For the evaluation of the antioxidant activity, FRAP and DPPH tests were carried out, and for the evaluation of the gastroprotective activity, gastric lesion induction by ethanol, acidified ethanol, indomethacin and physical barrier tests were used. Antioxidant assay of HELTF revealed an EC50 of 558.66 µM FeSO4/g and IC50 of 189.78 µg/ml for FRAP and DPPH respectively. In gastroprotective, in ethanol model, all the doses presented significant activity in comparison to controls, however, in the gastric lesion induction test by acidified ethanol and indomethacin, only the dose of 200 mg/kg presented with significance. In the physical barrier test presented evidence that protection by the formation of a protective layer associated with mucus. Concluded, therefore, that HELTF possesses antioxidant and significate gastroprotective activity.

Modulação in vitro da atividade antibiótica pelo óleo essencial dos frutos de Piper tuberculatum Jacq / Modulación in vitro de la actividad antibiótica por el aceite esencial de frutos de Piper tuberculatum Jacq / In vitro modulation of the antibiotic activity of essential oil from fruits of Piper tuberculatum Jacq

Introdução: Piper tuberculatum Jacq., popularmente conhecida como pimenta-longaou pimenta-d'Arda, é utilizada empiricamente no tratamento de doenças respiratórias (asma, bronquite e tosse) e digestivas (dores abdominais e diarreias). Na literatura é descrita com importantes atividades anti-inflamatória, antimicrobiana, antileucêmico e anti-helmíntica. Objetivos: avaliar a atividade moduladora do óleo essencial dos frutos de P. tuberculatum (OEPT) em associação com diferentes antibióticos frente à Staphylococcus aureus, Escherichia coli e Pseudomona aeruginosa. Metodos: Os frutos (frescos) de P. tuberculatum foram coletados em Barbalha/CE e submetidos à hidrodestilação em aparelho tipo Clevenger para ser extraído o óleo essencial, após a extração o óleo essencial foi tratado com sulfato de sódio anidro para eliminação da umidade residual. A avaliação da atividade antibacteriana e modulação (em resistência bacteriana) frente às cepas de S. aureus (SA358), E. coli (EC27) e P. aeruginosa (PA03) foram determinadas pelo método de microdiluição para identificar a concentração inibitória mínima (CIM), realizada em triplicata. CIM de ≤ 256 µg/mL foi considerado clinicamente relevante. Resultados: a atividade antibacteriana do OEPT exibiu um CIM de ≥ 1024 µg/mL contra as cepas de bactérias de padrão resistente a múltiplas drogas. Na avaliação da atividade moduladora, o OEPT antagonizou o efeito da amicacina contra E. coli e S. aureus, mas teve efeito sinérgico contra P. aeruginosa. Combinado com a getamicina o óleo exibiu antagonismo frente a E. coli, no entanto não apresentou resultado relevante contra S. aureas e P. aeruginosa. A associação do OEPT com o antibiótico imipenem resultou efeito mais relevante, apresentando sinergismo para todas as bactérias avaliadas, por outro lado, em associação com ciprofloxacino não apresentou efeito significante em relação ao controle. Conclusão: O OEPT apresentou uma melhor atividade quando associado ao imipenem frente todas as bactérias avaliadas, mostrando ser uma possível alternativa no desenvolvimento de novos fármacos com atividade antibacteriana advindos de produtos fitoterápicos(AU)

Introducción: Piper tuberculatum Jacq. popularmente conocida como pimenta-longa o pimenta-d'Arda, se utiliza empíricamente en el tratamiento de enfermedades respiratorias (asma, bronquitis y tos) y digestivas (dolor abdominal y diarrea). En la literatura es describe con importantes actividades antiinflamatorias, antimicrobianas, antileucémicas y antihelmínticas. Objetivo: evaluar la actividad moduladora de los aceites esenciales de frutos de P. tuberculatum (AEPT) en asociación con diferentes antibióticos contra Staphylococcus aureus, Escherichia coli y Pseudomona aeruginosa. Metodología: los frutos (frescos) de P. tuberculatum fueron recolectados en Barbalha/CE y sometidos a hidrodestilación en un equipo Clevenger, para extraer el aceite essencial (AEPT), el cual, una vez extraído, fue tratado con sulfato de sodio anhidro para eliminar la humedad residual. Se evaluó su actividad antibacteriana contra las cepas de S. aureus (SA358), E. coli (EC27) y P. aeruginosas (PA03). Empleando el método de microdilución se determinó la concentración inhibitoria mínima (CIM), con tres réplicas por cada tratamiento. Un valor de CIM ≤ 256 µg/mL se considera clínicamente relevante. Resultados: la actividad antibacteriana del AEPT exhibió una CIM ≥ 1024 µg/mL contra las cepas estándar de bacterias resistentes a múltiples fármacos. En efecto, la actividad AEPT antagoniza el efecto de amikacina contra E. coli y S. aureus, pero tenía un efecto sinérgico contra P. aeruginosa. Combinado con la getamicina el aceite exhibió antagonismo contra E. coli, sin embargo no presentó resultado relevante ante S. aureus y P. aeruginosa. La asociación de AEPT con el antibiótico imipenem resultó el efecto más relevante, mostrando sinergismo frente a todas las bacterias evaluadas. Por el contrario, en asociación con ciprofloxacina no mostró ningún efecto significativo con respecto al control. Conclusión: el AEPT presentó una mejor actividad cuando se asoció a imipenem, frente todas las bacterias evaluadas, demostrando ser una posible alternativa en el desarrollo de nuevos fármacos con actividad antimicrobiana, a partir de productos herbarios(AU)

Introduction: Piper tuberculatum Jacq., commonly known as pimenta-longa or pimenta-d'Arda, is empirically used to treat respiratory conditions (asthma, bronchitis and coughing) and digestive disorders (abdominal pain and diarrhea). Reference may be found in the literature to outstanding antiinflammatory, antimicrobial, antileukemic and antihelmintic activity. Objective: Evaluate the modulatory activity of essential oils from fruits of P. tuberculatum (AEPT) combined with various antibiotics againstStaphylococcus aureus, Escherichia coli and Pseudomona aeruginosa. Methods: Fresh fruits of P. tuberculatum were collected in Barbalha, CE, and subjected to hydrodistillation in a Clevenger set to extract the essential oil (AEPT). The oil extracted was then treated with anhydrous sodium sulfate to eliminate residual humidity. Antibacterial activity was evaluated against strains of S. aureus (SA358), E. coli (EC27) and P. aeruginosas (PA03). Minimum inhibitory concentration (MIC) was determined by the microdilution method, with three replications for each treatment. A MIC ≤ 256 µg/mL was considered to be clinically relevant. Results: Antibacterial activity of AEPT displayed a MIC of ≥1024 µg/mL against standard strains of multi-drug resistant bacteria. In fact, activity of AEPT antagonized the effect of amikacin against E. coli and S. aureus, but had a synergic effect against P. aeruginosa. Combined with gentamicin, the oil exhibited antagonism against E. coli, but no relevant result was obtained against S. aureus and P. aeruginosa. Combination of AEPT with the antibiotic imipenem had the most relevant effect, displaying synergism against all the bacteria evaluated. However, in combination with ciprofloxacin it did not show any significant effect with respect to the control. Conclusion: AEPT displayed better activity against all the bacteria evaluated when combined with imipenem, proving to be a possible alternative for the development of new herbal drugs with antimicrobial activity(AU)

Avaliação da atividade anti-Leishmania e anti-Trypanosoma do extrato etanólico das folhas de Annona squamosa L / Evaluation of the anti-leishmania and anti-trypanosoma activity of ethanolic extract from the leaves of Annona squamosa L

As doenças parasitárias, também chamadas de “doenças negligenciadas”, continuam sendo uma grande dificuldade para o desenvolvimento social e econômico dos países mais pobres. Podemos citar como exemplo dessas doenças, a leishmaniose e a doença de Chagas. A leishmaniose é causada por parasitas do gênero Leishmania e afeta cerca de 12 milhões de pessoas. A doença de Chagas, causada pelo protozoário Trypanosoma cruzi, causa aproximadamente 50.000 mortes por ano. Os fármacos disponíveis para o tratamento dessas doenças são altamente tóxicos, sendo este um dos motivos que leva à busca por drogas eficazes e seguras para seus tratamentos. As folhas da Annona squamosa, espécie da família Annonaceae, já foram descritas na literatura por suas atividades hepatoprotetora, antiparasitária, pesticida e antimicrobiana. Nesse estudo avaliamos a atividade anti-leishmania e tripanocida do extrato etanólico das folhas de Annona squamosa L. (EEAS) em formas promastigota do parasita Leishmania braziliensis e Leishmania infantum e epimastigota de Trypanosoma cruzi, além de avaliar a atividade citotóxica em fibroblasto. Os resultados demonstram que o extrato apresentou uma melhor atividade contra Leishmania infantum e Leishmania brasiliensis quando comparados com Trypanosoma cruzi; e que apresentou uma maior toxicidade nas concentrações de 500 e 1000 μg/ml, com mortalidade dos fibroblastos de aproximadamente 85% e 100%, respectivamente. Esse estudo aponta para uma perspectiva terapêutica alternativa que se mostrou eficaz frente aos parasitas aqui estudados, exceto a forma epimastigota de Trypanosoma cruzi. Com relação aos testes de citotoxicidade fazem-se necessários novos testes, uma vez que apresentou um alto nível de toxicidade, viabilizando assim futuros ensaios in vivo.

The parasitic diseases, also calls by “neglected diseases”, continue being a major difficulty for the social and economic development of the poorest countries. We can cite as an example of these diseases, the leishmaniasis and the Chagas disease. Leishmaniasis is caused by parasites of the genus Leishmania and affects about 12 million people. The Chagas disease, caused by the protozoan Trypanosoma cruzi, causes approximately 50,000 deaths per year. The drugs available for the treatment of these diseases are highly toxic, being this one of the reasons that leads to the search for effective and safe drugs for their treatments. The leaves of the Annona squamosa, species of the family Annonaceae, have already been described in the literature by their hepatoprotective activities, antiparasitic, pesticide and antimicrobial. In this study we assessed the activity tripanocidal and antileishmania of ethanolic extract from the leaves of Annona squamosa L. (EEAS) in promastigota forms of the parasite Leishmania braziliensis and Leishmania infantum and epimastigota of Trypanosoma cruzi, in addition to evaluating the cytotoxic activity in fibroblasts. The results demonstrate that the extract presented a better activity against Leishmania infantum and Leishmania brasiliensis when compared with Trypanosoma cruzi; and which presented a greater toxicity at concentrations of 500 and 1000 μg/ml, with mortality of fibroblasts of approximately 85% and 100%, respectively. This study points to an alternative therapeutic perspective that showed effective against the parasites here studied, except the epimastigota form of Trypanosoma cruzi. With relation to cytotoxicity tests are required new tests, once presented a high level of toxicity, thus enabling future in vivo assays.

Atividade moduladora sobre antibióticos pelo extrato aquoso das folhas de Bauhinia ungulata L / Actividad modulador acerca de antibióticos por el extracto acuoso de las hojas de Bauhinia ungulata l / Modulatory activity about antibiotics by aqueous extract of the leaves of Bauhinia ungulata l

Introdução: cepas de Staphylococcus aureus, Escherichia coli e Pseudomonas aeruginosa são caracterizadas como importantes causadores de infeções bacterianas e destacam-se como um preocupante problema de saúde pública. A atividade antibacteriana de várias plantas tem sido estudada com a finalidade de diminuir a resistência microbiana existente com relação aos fármacos já industrializados. O gênero Bauhinia compreende cerca de 300 espécies que são conhecidas no Brasil como pata-de-vaca. A espécie Bauhinia ungulata Lin é bastante utilizada no controle glicêmico, mas, também, apresenta outras atividades, dentre elas é relatado uma ação antibacteriana. Objetivo: verificar o potencial modulador da espécie B. ungulata em associação a outros medicamentos já testados contra cepas de S. aureus, E. coli e P. aeruginosa. Métodos: as folhas da B. ungulata Lin foram coletadas no distrito de Arajara, Chapada do Araripe, estado do Ceará, Brasil. Foi utilizado o extrato aquoso das folhas de Bauhinia ungulata em associação aos antibióticos Amicacina, Gentamicina, Imipenem e Ciprofloxacino, esperando que o extrato agisse com antagonismo ou sinergismo frente ao efeito dos antibióticos. Resultados: o extrato das folhas de B. ungulata Lin apresentou relevante atividade sinérgica sobre os antibióticos utilizados (amicacina, gentamicina, imipenem e ciprofloxacino). Conclusão: portanto, o extrato em associação com os fármacos potencializou o efeito destes, revelando uma atividade antibacteriana significante(AU)

Introducción: las cepas de Staphylococcus aureus, Escherichia coli e Pseudomonas aeruginosa son causa importante de infecciones bacterianas y se destacan como un problema de salud pública. La actividad antibacteriana de varias plantas se ha estudiado con el fin de reducir la resistencia microbiana existente con respecto a los medicamentos ya industrializados. El género Bauhinia comprende alrededor de 300 especies que se les conoce en Brasil como pata-de-vaca. La especie Bauhinia ungulata Lin es ampliamente utilizada en control de la glucemia, pero también ofrece otras actividades, entre ellas es divulgado una acción antibacteriana. Objetivo: verificar el potencial modulador de las especies B. ungulata en asociación con otros fármacos probados contra cepas de S. aureus, E. coli y P. aeruginosa. Métodos: las hojas de B. ungulata Lin fueron recolectados en el distrito de Arajara, Chapada do Araripe, estado de Ceará, Brasil. Se utilizó el extracto acuoso de hojas de B. ungulata en asociación con antibióticos amikacina, gentamicina imipinem y ciprofloxacina, con la esperanza de que el extracto actúa con antagonismo o sinergismo, delantero de los efectos de los antibióticos. Resultados: el extracto de las hojas de B. ungulata Lin presenta relevante actividad sinérgica de los antibióticos utilizados (amikacina, gentamicina, ciprofloxacina y imipinem). Conclusión: el extracto en asociación con las drogas aumentó el efecto de estos, revelando una significativa actividad antibacteriana(AU)

Introduction: strains of Staphylococcus aureus, Escherichia coli e Pseudomonas aeruginosa are characterized as important causes of bacterial infections and stand out as a worrying public health problem. The antibacterial activity of several plants has been studied for the purpose of reducing the existing microbial resistance with respect to drugs already industrialized. The genus Bauhinia it comprises about 300 species they are known in Brazil as pata-de-vaca. The specie Bauhinia ungulata Lin is widely used in glycemic control, but also features other activities, among them is reported an antibacterial action. Objective: to verify the potential modulator of the species B. ungulata in association with other drugs tested against strains of S. aureus, E. coli and P. aeruginosa. Methods: The leaves of B. ungulata Lin were collected in the District of Arajara, Chapada do Araripe, Ceará state, Brazil. We used the water extract of leaves of B. ungulata in association with antibiotics amikacin, gentamicin, imipinem and ciprofloxacin, hoping that the extract acted with antagonism or synergism, front of the effects of antibiotics. Results: the extract of the leaves of B. ungulata Lin presented relevant synergistic activity about the antibiotics used (amikacin, gentamicin, ciprofloxacin and imipinem). Conclusion: therefore, the extract in association with the drugs increased the effect of these, revealing a significant antibacterial activity(AU)