Chemical composition of Piper gaudichaudianum Kunth essential oil and evaluation of its antimicrobial and modulatory effects on antibiotic resistance, antibiofilm, and cell dimorphism inhibitory activities.

Essential oils extracted from many plant species have different biological activities, among which microbial activity stands out. Species of the genus Piper have antimicrobial potential against different species of bacteria and fungi. In this sense, the present study aimed to determine the chemical composition of the essential oil from the leaves of Piper gaudichaudianum (EOPG), as well as to investigate their antimicrobial activity and their modulatory effect on the Norfloxacin resistance in the Staphylococcus aureus SA1199B strain overproducer of the NorA efflux pump. Furthermore, their inhibitory activities on the biofilm formation as well as on the cellular differentiation of C. albicans were evaluated. Gas chromatography analysis identified 24 compounds, such as hydrocarbon sesquiterpenes (54.8%) and oxygenated sesquiterpenes (28.5%). To investigate the antimicrobial potential of EOPG against S. aureus, E. coli, and C. albicans, a microdilution assay was performed, and no intrinsic antimicrobial activity was observed. On the other hand, the oil potentiated the activity of Norfloxacin against the SA1199B strain, indicating that EOPG could be used in association with Norfloxacin against S. aureus strains resistant to this antibiotic. EOPG also inhibited S. aureus biofilm formation, as evidenced by the crystal violet assay. In the dimorphism assay, EOPG was able to inhibit the cell differentiation process in C. albicans. Results indicate that EOPG could be used in association with Norfloxacin in the treatment of infections caused by resistant S. aureus strains overproducing the NorA efflux pump. Furthermore, its ability to inhibit the formation of hyphae by C. albicans suggests that EOPG could also be applied in the prevention and/or treatment of fungal infections.

Chemical composition and potentiating action of Norfloxacin mediated by the essential oil of Piper caldense C.D.C. against Staphylococcus aureus strains overexpressing efflux pump genes.

Infectious diseases caused by multidrug-resistant microorganisms has increased in the last years. Piper species have been reported as a natural source of phytochemicals that can help in combating fungal and bacterial infections. This study had as objectives characterize the chemical composition of the essential oil from Piper caldense (EOPC), evaluate its potential antimicrobial activity, and investigate the synergistic effect with Norfloxacin against multidrug-resistant S. aureus overproducing efflux pumps, as well as, verify the EOPC ability to inhibit the Candida albicans filamentation. EOPC was extracted by hydrodistillation, and the chemical constituents were identified by gas chromatography, allowing the identification of 24 compounds (91.9%) classified as hydrocarbon sesquiterpenes (49.6%) and oxygenated sesquiterpenes (39.5%). Antimicrobial tests were performed using a 96-well plate microdilution method against C. albicans ATCC 10231, Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 standard strains, as well as against multidrug-resistant strains S. aureus SA1199B (overexpressing norA gene), S. aureus K2068 (overexpressing mepA gene) and S. aureus K4100 (overexpressing qacC gene). The oil showed activity against C. albicans ATCC 10231 (≥ 512 µg/mL) and was able to inhibit hyphae formation, an important mechanism of virulence of C. albicans. On the other hand, EOPC was inactive against all bacterial strains tested (≤ 1,024 µg mL). However, when combined with Norfloxacin at subinhibitory concentration EOPC reduced the Norfloxacin and Ethidium bromide MIC values against S. aureus strains SA1199B, K2068 and K4100. These results indicate that EOPC is a source of phytochemicals acting as NorA, MepA and QacC inhibitors.

Antifungal activity of farnesol incorporated in liposomes and associated with fluconazole.

Candida infections represent a threat to human health. Candida albicans is the main causative agent of invasive candidiasis, especially in immunosuppressed patients. The emergence of resistant strains has required the development of new therapeutic strategies. In this context, the use of liposomes as drug carrier systems is a promising alternative in drug development. Thus, considering the evidence demonstrating that sesquiterpene farnesol is a bioactive compound with antifungal properties, this study evaluated the activity farnesol-containing liposomes against different Candida strains. The IC50 of farnesol and its liposomal formulation was assessed in vitro using cultures of Candida albicans, Candida tropicalis, and Candida krusei. The Minimum Fungicidal Concentration (MFC) was established by subculture in solid medium. The occurrence of fungal dimorphism was analyzed using optical microscopy. The effects on antifungal resistance to fluconazole were assessed by evaluating the impact of combined therapy on the growth of Candida strains. The characterization of liposomes was carried out considering their vesicular size, polydispersion index, and zeta medium potential, in addition to electron microscopy analysis. Farnesol exerted an antifungal activity that might be associated with the inhibition of fungal dimorphism, especially in Candida albicans. The incorporation of farnesol into liposomes significantly increased its antifungal activity against C. albicans, C. tropicalis, and C. krusei. In addition, liposomal farnesol potentiated the action of fluconazole against C. albicans and C. tropicalis. On the other hand, the association of unconjugated farnesol with fluconazole resulted in antagonistic effects. In conclusion, farnesol-containing liposomes have the potential to be used in antifungal drug development. However, further research is required to investigate how the antifungal properties of farnesol are affected by the interaction with liposomes, contributing to the modulation of antifungal resistance to conventional drugs.

Antifungal Properties of Nerolidol-Containing Liposomes in Association with Fluconazole.

(1) Background: Infections by Candida species represent a serious threat to the health of immunocompromised individuals. Evidence has indicated that nerolidol has significant antifungal properties. Nonetheless, its use is restricted due to a low water solubility and high photosensitivity. The incorporation into liposomes may represent an efficient alternative to improve the physicochemical and biopharmaceutical properties of this compound. The present study aimed to characterize the antifungal properties of liposomal nerolidol, alone or in combination with fluconazole. Of note, this is the first study reporting the antifungal activity of liposomal nerolidol and its potentiating effect in association with fluconazole. (2) Methods: The Inhibitory Concentration 50%-IC50 and minimum fungicide concentrations (MFC) of the substances against Candida albicans (CA), Candida tropicalis (CT), and Candida krusei (CK) were established by subculture in a solid medium. To evaluate the antifungal-enhancing effect, the MFC of fluconazole was determined in the presence or absence of subinhibitory concentrations of nerolidol (free or liposomal). The analysis of fungal dimorphism was performed through optical microscopy and the characterization of liposomes was carried out considering the vesicular size, polydispersion index, and zeta medium potential, in addition to a scanning electron microscopy analysis. (3) Results: The physicochemical characterization revealed that liposomes were obtained as homogenous populations of spherical vesicles. The data obtained in the present study indicate that nerolidol acts as an antifungal agent against Candida albicans and Candida tropicalis, in addition to potentiating (only in the liposomal form) the effect of fluconazole. However, the compound had little inhibitory effect on fungal dimorphism. (4) Conclusions: The incorporation of nerolidol into liposomes improved its antifungal-modulating properties.

Chalcones Isolated from Arrabidaea brachypoda Flowers as Inhibitors of NorA and MepA Multidrug Efflux Pumps of Staphylococcus aureus.

Bacterial resistance to antibiotics has become a public health issue around the world. The present study aimed to evaluate the antibacterial activity of chalcones isolated from flowers of Arrabidaea brachypoda, and their potential as efflux pump inhibitors of Staphylococcus aureus efflux pumps. Microdilution assays were performed with natural products from A. brachypoda. Chalcones 1, 3, 4, and 5 did not show intrinsic antimicrobial activity against all S. aureus strains tested, but they were able to potentiate the Norfloxacin action against the SA1199-B (norA) strain, with a better modulating action for the 4 trimethoxylated chalcone. All chalcones were also able to potentiate the action of EtBr against SA1199-B strain, suggesting a potential NorA inhibition. Moreover, chalcone 4 was able to interfere in the activity of MepA, and interfered weakly in the QacA/B activity. Molecular docking analyzes showed that tested chalcones are capable of binding in the hydrophobic cavity of NorA and MepA, in the same Norfloxacin binding site, indicating that chalcone 4 compete with the antibiotic for the same NorA and MepA binding sites. Association of chalcone 4 with Norfloxacin could be an alternative against multidrug resistant S. aureus over-productive of NorA or MepA.

Antimicrobial activity and inhibition of the NorA efflux pump of Staphylococcus aureus by extract and isolated compounds from Arrabidaea brachypoda.

Arrabidaea brachypoda is a native shrub of the Brazilian Cerrado widely used in the folk medicine for treatment of renal diseases and articular pains. This study aimed to, first, evaluate the antimicrobial activity of both extracts and isolated molecules Brachydins BR-A and BR-B obtained from the flowers of A. brachypoda against Staphylococcus aureus, Escherchia coli and Candida albicans species. A second objective was to investigate if these natural products were able to potentiate the Norfloxacin activity against the strain Staphylococcus aureus SA1199-B that overexpress the norA gene encoding the NorA efflux pump. Extracts and isolated compounds were analyzed by HPLC-PDA and LC-ESI-MS respectively. Minimal inhibitory concentrations of Norfloxacin or Ethidium Bromide (EtBr) were determined in the presence or absence of ethanolic extract, dichloromethane fraction, as well as BR-A or BR-B by microdilution method. Only BR-B showed activity against Candida albicans. Addition of ethanolic extract, dichloromethane fraction or BR-B to the growth media at sub-inhibitory concentrations enhanced the activity of both Norfloxacin and EtBr against S. aureus SA1199-B, indicating that these natural products and its isolated compound BR-B were able to modulate the fluoroquinolone-resistance possibly by inhibition of NorA. Moreover, BR-B inhibited the EtBr efflux in the SA1199-B strain confirming that it is a NorA inhibitor. Isolated BR-B was able to inhibit an important mechanism of multidrug-resistance very prevalent in S. aureus strains, thus its use in combination with Norfloxacin could be considered as an alternative for the treatment of infections caused by S. aureus strains overexpressing norA.

Tagetes spp. Essential Oils and Other Extracts: Chemical Characterization and Biological Activity.

Tagetes (marigold) is native to America, and its cultivation currently extends to other countries in Africa, Asia, and Europe. Many species of this genus, such as T. minuta, T. erecta, T. patula, and T. tenuifolia, are cultivated as ornamental plants and studied for their medicinal properties on the basis of their use in folk medicine. Different parts of the Tagetes species are used as remedies to treat various health problems, including dental, stomach, intestinal, emotional, and nervous disorders, as well as muscular pain, across the world. Furthermore, these plants are studied in the field of agriculture for their fungicidal, bactericidal, and insecticidal activities. The phytochemical composition of the extracts of different Tagetes species parts are reported in this work. These compounds exhibit antioxidant, antiinflammatory, and enzyme inhibitory properties. Cultivation and the factors affecting the chemical composition of Tagetes species are also covered. In the current work, available literature on Tagetes species in traditional medicine, their application as a food preservative, and their antimicrobial activities are reviewed.

Use of Flavonoids and Cinnamates, the Main Photoprotectors with Natural Origin.

Many pathological problems are initiated by ultraviolet radiation (UVR), such as skin cancer, the most commonly diagnosed cancer worldwide. The UVA (320-400 nm) and UVB (290-320 nm) wavelengths may cause effects such as photoaging, DNA damage, and a series of cellular alterations. The UVA radiation can damage the DNA, oxidize the lipids, and produce dangerous free radicals, which can cause inflammation, modify the gene expression in response to stress, and weaken the skin immune response. With a minor penetration, the UVB radiation is more harmful, being responsible for immediate damage. Ultraviolet radiation light emitted by the sun is considered necessary for the existence of life but cause radiation problems, especially in the skin. The photoprotective activities of plant extracts and isolated composts were evaluated by many reports, as well as the correlation of these compounds with the antioxidant activity. This review presents plant compounds with interest to the cosmetic industry to be used in sunscreens such as flavonoids and cinnamates.