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Strategies based on natural modulators

Natural approaches in patient treatment, as well as green synthesis routes of pharmacological compounds, have been continuously developed since it was understood that often natural therapies could bring undeniable advantages. To begin with, bioactive compounds could be easily extracted, and since they manifest less toxicity, the safety of the receiving patient is enhanced. Furthermore, the diversity of natural bioactive compounds allows the development of numerous strategies and combinations, resulting in the versatility and the undeniably wider applicability compared to the standard chemical treatments.

Essential oils

A 2016 article reported the promising activity of mandarin essential oils toward bacterial virulence inhibition. The study determined the adequate concentrations of various samples of cold pressing mandarin essential oils, with or without further purification, which could help inhibit Pseudomonas aeruginosa biofilms. The natural compounds were tested on two antibiotic-resistant strains of P. aeruginosa isolated from clinical samples. For both strains, the antibacterial behavior of the essential oils as a whole and of their main compound, limonene, were evaluated. The study concluded that mandarin essential oils exhibit a moderate antibacterial effect toward P. aeruginosa cultures when utilized in lower concentration, but can be used to inhibit the biofilm development. Moreover, it highlighted the fact that the essential oils subjected to distillation determine a higher mortality rate among the microbial strains, being more efficient than purified limonene (Luciardi et al., 2016).

The antibacterial effects of Eucalyptus globules and Eucalyptus radiata essential oils proved antimicrobial effects against several Gram-negative bacterial strains, such as Acinetobacter baumannii. Authors reveal a synergistic effect of the natural compounds and commonly used antibiotics (such as chloramphenicol, ciprofloxacin, tetracycline). In the same paper, the antioxidant properties of both essential oils were investigated and debated. The experiment aimed at determining the inhibitory and bactericidal activity of the naturally occurring polyphenols, and also tested their impact on biofilm development and virulence. Both oils manifested remarkable antibacterial activity and synergistic effects with the conventional antibiotics employed in the test, overall, showing promising behavior. The results lead to the idea that antimicrobial properties of tested oils are based on the capacity to inhibit lipid peroxidation and on their radical scavenging properties (Luis et al., 2016).

Knezevic et al. (2016) also reported the synergistic effects of eucalyptus essential oils, extracted from Eucalyptus camaldulensis leaves, and ciprofloxacin, gentamicin, and polymyxin B toward drug-resistant A. baumannii strains. The extracts exhibited remarkable bacteriostatic and bactericidal activity against all the A. baumannii strains employed in the study. This result was explained by the presence of various compounds with potential antimicrobial activity: 1,8-cineole, p-cymene, and y-terpinene that could consist up to 22% of the composition of these essential oils. The quantified synergistic effects varied with both the strains and the chemically synthesized drug (Knezevic et al., 2016). Both studies come in support of traditionally employed herbal treatments that have been used by various populations, thus also highlighting their ethnopharmacological relevance (Luis et al., 2016; Knezevic et al., 2016).

In a detailed study by Moussaoui and Alaoui (2016), the antibacterial effect of five essential oils extracted from Origanum compactum, Chrysanthemum coronarium, Thymus willdenowii Boiss, Melissa officinalis, and Origanum majorana was assessed.

The natural compounds were also tested in combination with standard antibiotics, for a comparative evaluation. Gentamicin, tobramycin, imipenem, and tircarcillin were chosen to determine the synergistic effects of the natural oils. For the evaluation of antibacterial activity, the authors employed the disk diffusion method. Essential oils and mixtures of essential oils and antibiotics (AB) were tested on a broad spectrum of both Gram-positive and Gram-negative bacteria such as Staphylococcus aureus (S. aureus) (Gram-positive), and Escherichia coli (E. coli), Klebsiella pneumoniae, Proteus mirabilis, P. aeruginosa, Pseudomonasputida, Salmonella enteritidis, and Enterobacter aerogenes (Gram-negative). According to the results, the essential oils act in synergy with some widely utilized antibiotics and, moreover, impair on their own the viability of most tested strains. Nonetheless, in some cases, an antagonistic effect was observed among tested essential oils (Moussaoui and Alaoui, 2016).

A team led by Khosravi focused on developing a new approach for treating infections caused by isolates of pathogenic fungal species. They tested a series of essential oils extracted from Zataria multiflora, Thymus kotschyanus, Menthaspicata, Artemisia sieberi, Rosmarinus officinalis, and Heracleum persicum. The antifungal properties were thoroughly investigated and discussed in this chapter. The most promising effects were shown by the Z. multifloram and T. kotschyanus essential oils, which consistently decreased the viability of pathogenic yeast from low concentration (Khosravi et al., 2015).

The advantageous combination of essential oils with conventional antibiotics was also investigated in a study employed by Valcourt et al. Major compounds extracted from oregano, clove, and cinnamon oils, carvacrol, eugenol, and cinnamaldehyde, respectively, were encapsulated in lipid nanocapsules whose drug loading was calculated at 20%. Time-kill assay and checkboard titration were the methods used to determine the effect the bioactive substance-loaded lipid nanocapsule and an antibiotic (doxycycline) manifest toward a series of five Gram-negative bacterial strains: A. baumannii SAN, A. baumannii RCH, K. pneumoniae, E. coli, and P aeruginosa. The synergistic interaction manifested only in terms of bactericidal effects against all strains; however, the interaction between the natural extracts and the antibiotic did not inhibit the growth (Valcourt et al., 2016).

In a 2016 study, Gelmini et al. developed a novel system based on dispersed essential oils meant to control environmental microbiota and sanitize hospital room to prevent nosocomial infections. Authors state that essential oils can be vaporized in combination with sanitization procedures commonly used in hospitals, according to the current standards. Pilot studies reported that the procedure is efficient for both bacterial and fungal contamination reduction (Gelmini et al., 2016).

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