The essential oil of Melaleuca alternifolia incorporated into hydrogel induces antimicrobial and anti-inflammatory effects on infected wounds by Staphylococcus aureus.

Staphylococcus aureus is one of the most common bacterial isolates found in wounds. Thus, innovative dressings, such as hydrogels, are interesting vehicles for incorporating bioactive compounds like those from Melaleuca alternifolia essential oil (MaEO). In this study, we evaluated the antimicrobial and anti-inflammatory potential of MaEO incorporated into an alginate and chitosan hydrogel for treating wounds infected by S. aureus. The hydrogel incorporated with MaEO 1% (HMa 1%) was homogeneous with a bright pale-yellow color and the characteristic smell of Melaleuca. The incorporation of MaEO 1% does not affect the stability of the hydrogel, which was stable up to 90 days of storage. The Scanning electron microscopy analysis revealed that hydrogels showed irregular surfaces and interconnected porous structures with accumulations of oil crystals distributed throughout the formulation. HMa 1% has a high moisture content (95.1%) and can absorb simulated wound fluid. Regarding the antimicrobial effects, HMa 1% reduced the growth of S. aureus ATCC 6538 in both in vitro conditions and in an ex vivo model of wounds using porcine skin. In addition, the dairy topical treatment of murine skin lesions with HMa 1% induced a significant reduction of the wound area, inflammation score, and bacterial load, as well as tissue re-epithelialization and modulation of inflammatory mediators. Therefore, hydrogel incorporated with MaEO 1% has excellent potential to be used in the pharmacotherapy of infected wounds.

Cinnamaldehyde for the Treatment of Microbial Infections: Evidence Obtained from Experimental Models.

Cinnamaldehyde (CNM) is a cyclic terpene alcohol found as the major compound of essential oils from some plants of the genus Cinnamomum (Lauraceae). CNM has several reported pharmacological activities, including antimicrobial, antivirulence, antioxidant, and immunomodulatory effects. These properties make CNM an attractive lead molecule for the development of anti-infective agents. In this descriptive review, we discuss the application of CNM in experimental models of microbial infection using invertebrate and vertebrate organisms. CNM (pure or in formulations) has been successfully applied in the treatment of infections caused by a range of bacterial (such as Cronobacter sakazakii, Escherichia coli, Listeria monocytogenes, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Salmonella enterica, Staphylococcus aureus, Streptococcus agalactiae, Vibrio cholerae) and fungal (such as Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans) pathogens. All these experimental evidence-based findings have promoted the use of cinnamaldehyde as the leading molecule for developing new anti- infective drugs.

Asteraceae Plants as Sources of Compounds Against Leishmaniasis and Chagas Disease.

Leishmaniasis and Chagas disease cause great impact on social and economic aspects of people living in developing countries. The treatments for these diseases are based on the same regimen for over 40 years, thus, there is an urgent need for the development of new drugs. In this scenario, Asteraceae plants (a family widely used in folk medicine worldwide) are emerging as an interesting source for new trypanocidal and leishmanicidal compounds. Herein, we provide a non-exhaustive review about the activity of plant-derived products from Asteraceae with inhibitory action toward Leishmania spp. and T. cruzi. Special attention was given to those studies aiming the isolation (or identification) of the bioactive compounds. Ferulic acid, rosmarinic acid, and ursolic acid (Baccharis uncinella DC.) were efficient to treat experimental leishmaniasis; while deoxymikanolide (Mikania micrantha) and (+)-15-hydroxy-labd-7-en-17-al (Aristeguietia glutinosa Lam.) showed in vivo anti-T. cruzi action. It is also important to highlight that several plant-derived products (compounds, essential oils) from Artemisia plants have shown high inhibitory potential against Leishmania spp., such as artemisinin and its derivatives. In summary, these compounds may help the development of new effective agents against these neglected diseases.

Hydroalcoholic Extract and Ethyl Acetate Fraction of Bixa orellana Leaves Decrease the Inflammatory Response to Mycobacterium abscessus Subsp. massiliense.

The incidence of infections caused by rapidly growing mycobacteria (RGM), especially Mycobacterium abscessus subsp. massiliense (Mabs), is increasing worldwide. Severe infections are associated with abscess formation and strong inflammatory response. This study evaluated the antimicrobial and anti-inflammatory activities of a hydroalcoholic extract (BoHE) and ethyl acetate fraction (BoEA) of Bixa orellana leaves. Antimicrobial activity was evaluated by broth microdilution to determine the minimum inhibitory (MIC) and the minimum bactericidal (MBC) concentrations. Cytotoxicity was evaluated using erythrocytes and RAW 264.7 cells. Nitric oxide (NO) was assayed in stimulated RAW 264.7 cells, and inflammatory cell migration and acute toxicity were evaluated in a Mabs-induced peritonitis mouse model. The compounds present in BoEA were identified by high performance liquid chromatography and mass spectrometry (HPLC-MS). The MIC and MBC values were 2.34 mg/mL and 37.5 mg/mL for BoHE and 0.39 mg/mL and 6.25 mg/mL for BoEA. The extracts did not induce significant toxicity in erythrocytes and RAW 264.7 cells. High levels of NO induced by Mabs were decreased by treatment with both extracts. The anti-inflammatory activity was confirmed in vivo by significant reduction of the cell migration to the peritoneum following BoHE and BoEA pretreatment. Animals treated with BoHE or BoEA did not show signs of acute toxicity in stomach, liver, and kidney. The chemical characterization of BoEA (the most active extract) revealed that kaempferol-3-O-coumaroyl glucose is its major component. The extract of B. orellana may be effective for treating infections caused by Mabs.

Hexane extract from Spondias tuberosa (Anacardiaceae) leaves has antioxidant activity and is an anti-Candida agent by causing mitochondrial and lysosomal damages.

BACKGROUND: Spondias tuberosa is a plant that produces a fruit crop with high economic relevance at Brazilian Caatinga. Its roots and leaves are used in folk medicine. METHODS: Chemical composition of a hexane extract from S. tuberosa leaves was evaluated by thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and 1H nuclear magnetic resonance (NMR). Antioxidant potential was investigated by DPPH and ABTS assays. Antifungal action on Candida species was evaluated determining the minimal inhibitory concentration (MIC50) and putative mechanisms were determined by flow cytometry analysis. In addition, hemolytic activity on human erythrocytes was assessed and the concentration required to promote 50% hemolysis (EC50) was determined. RESULTS: Phytochemical analysis by TLC showed the presence of flavonoids, hydrolysable tannins, saponins and terpenes. The HPLC profile of the extract suggested the presence of gallic acid (0.28 ± 0.01 g%) and hyperoside (1.27 ± 0.01 g%). The representative 1H NMR spectrum showed saturated and unsaturated fatty acids among the main components. The extract showed weak and moderate antioxidant activity in DPPH (IC50: 234.00 µg/mL) and ABTS (IC50: 123.33 µg/mL) assays, respectively. It was able to inhibit the growth of C. albicans and C. glabrata with MIC50 of 2.0 and 0.078 mg/mL, respectively. The treatment of C. glabrata cells with the extract increased levels of mitochondrial superoxide anion, caused hyperpolarization of mitochondrial membrane, and compromised the lysosomal membrane. Weak hemolytic activity (EC50: 740.8 µg/mL) was detected. CONCLUSION: The results demonstrate the pharmacological potential of the extract as antioxidant and antifungal agent, aggregating biotechnological value to this plant and stimulating its conservation.

Antibacterial activity of endophytic fungi from leaves of Indigofera suffruticosa Miller (Fabaceae).

Endophytic fungi were isolated from healthy leaves of Indigofera suffruticosa Miller, a medicinal plant found in Brazil which is used in folk medicine to treat various diseases. Among 65 endophytic fungi isolated, 18 fungi showed activity against at least one tested microorganism in preliminary screening, and the best results were obtained with Nigrospora sphaerica (URM-6060) and Pestalotiopsis maculans (URM-6061). After fermentation in liquid media and in semisolid media, only N. sphaerica demonstrated antibacterial activity (in Potato Dextrose Broth-PDB and in semisolid rice culture medium). In the next step, a methanolic extract from rice culture medium (NsME) and an ethyl acetate extract (NsEAE) from the supernatant of PDB were prepared and both exhibited antimicrobial activity against Gram-negative and Gram-positive bacteria. The best result was observed against Staphylococcus aureus, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of 1.56 mg/mL and 6.25 mg/mL, respectively, for NsME and MIC and MBC values of 0.39 mg/mL and 3.12 mg/mL, respectively, for NsEAE. This study is the first report about the antimicrobial activity of endophytic fungi residing in I. suffruticosa leaves, in which the fungus N. sphaerica demonstrated the ability to produce bioactive agents with pharmaceutical potential, and may provide a new lead in the pursuit of new biological sources of drug candidates.

Anti-Staphylococcus aureus action of three Caatinga fruits evaluated by electron microscopy.

This study evaluated the antibacterial activity of Anadenanthera colubrina, Libidibia ferrea and Pityrocarpa moniliformis fruit extracts against clinical strains of Staphylococcus aureus. The samples were active for all S. aureus strains (minimum inhibitory concentration: 0.38-3.13 mg mL⁻¹), including the multiresistant strain. The morphological changes suggested the cell wall as the main action target. The treated-cells also lose their ability to form aggregates. The analysis suggests cell wall impairment, which causes the loss of viability and death. This study showed for the first time the morphologic alterations involved in the anti-S. aureus action of fruits of A. colubrina, L. ferrea and P. moniliformis. These findings indicated that these fruit extracts are sources of bioactive compounds that can be used as antibacterial agents.

Comparative analysis of the antioxidant and DNA protection capacities of Anadenanthera colubrina, Libidibia ferrea and Pityrocarpa moniliformis fruits.

This study aimed to explore the antioxidant and DNA protection abilities of hydroalcoholic extracts from fruits of Anadenanthera colubrina (ACHE), Libidibia ferrea (LFHE) and Pityrocarpa moniliformis (PMHE). These extracts were tested by five antioxidant methods (phosphomolibdenium and reducing power assays; superoxide, hydrogen peroxide and nitric oxide scavenging) and DNA protection capacity. Total phenolic content was measured by Folin-Ciocalteu method. ACHE exhibited the highest phenolic content (578 mg/g GAE), followed by LFHE (460 mg/g GAE) and PMHE (448 mg/g GAE). In phosphomolibdenium assay, ACHE showed 24.81% of activity in relation to ascorbic acid, whereas LFHE and PMHE had 21.08% and 18.05%, respectively. These plants showed high ability to inhibit reactive species tested with IC50 values ranged from 10.66 to 14.37 µg/mL for superoxide radical; 26.05 to 45.43 µg/mL for hydrogen peroxide; 178.42 to 182.98 µg/mL for reducing power; and 199.2 to 283 µg/mL for nitric oxide. Furthermore, these extracts had capacity to break the DNA damage induced by hydroxyl radicals. The antioxidant activity of these plants is related with their higher phenolic content and show that they may be used as source of bioactive compounds, relevant to the maintenance of oxidative stability of the food matrix, cosmetics and/or pharmaceutical preparations.