Phytochemicals: A Promising Weapon in the Arsenal against Antibiotic-Resistant Bacteria.

The extensive usage of antibiotics and the rapid emergence of antimicrobial-resistant microbes (AMR) are becoming important global public health issues. Many solutions to these problems have been proposed, including developing alternative compounds with antimicrobial activities, managing existing antimicrobials, and rapidly detecting AMR pathogens. Among all of them, employing alternative compounds such as phytochemicals alone or in combination with other antibacterial agents appears to be both an effective and safe strategy for battling against these pathogens. The present review summarizes the scientific evidence on the biochemical, pharmacological, and clinical aspects of phytochemicals used to treat microbial pathogenesis. A wide range of commercial products are currently available on the market. Their well-documented clinical efficacy suggests that phytomedicines are valuable sources of new types of antimicrobial agents for future use. Innovative approaches and methodologies for identifying plant-derived products effective against AMR are also proposed in this review.

New Insight into Vitamins E and K1 as Anti-Quorum-Sensing Agents against Pseudomonas aeruginosa.

Today, antivirulence compounds that attenuate bacterial pathogenicity and have no interference with bacterial viability or growth are introduced as the next generation of antibacterial agents. However, the development of such compounds that can be used by humans is restricted by various factors, including the need for extensive economic investments, the inability of many molecules to penetrate the membrane of Gram-negative bacteria, and unfavorable pharmacological properties and cytotoxicity. Here, we take a new and different look into two frequent supplements, vitamin E and K1, as anti-quorum-sensing agents against Pseudomonas aeruginosa, a pathogen that is hazardous to human life and responsible for several diseases. Both vitamins showed significant anti-biofilm activity (62% and 40.3% reduction by vitamin E and K1, respectively), and the expression of virulence factors, including pyocyanin, pyoverdine, and protease, was significantly inhibited, especially in the presence of vitamin E. Cotreatment of constructed biofilms with these vitamins plus tobramycin significantly reduced the number of bacterial cells sheltered inside the impermeable matrix (71.6% and 69% by a combination of tobramycin and vitamin E or K1, respectively). The in silico studies, besides the similarities of chemical structures, reinforce the possibility that both vitamins act through inhibition of the PqsR protein. This is the first report of the antivirulence and antipathogenic activity of vitamin E and K1 against P. aeruginosa and confirms their potential for further research against other multidrug-resistant bacteria.

Saccharomyces cerevisiae as a delivery system of Zataria multiflora Boiss. essential oil as a natural preservative for food applications: Encapsulation of Iranian Zataria multiflora Boiss. essential oil.

BACKGROUND: The following study is an evaluation of the encapsulation, stability and release profile of Iranian Zateria multiflora boiss essential oil (ZEO) in Saccharomyces cerevisiae yeast cells. Encapsulation was performed with different essential oil / yeast weight ratios at different temperatures. The encapsulation efficiency and stability of the loaded yeasts and the release profiles of carvacrol and thymol (as the main active ingredients of ZEO) were also investigated. RESULT: The encapsulation efficiencies of carvacrol and thymol at a ZEO / yeast weight ratio of 1.25 were 30.9% ± 0.01% and 44.5% ± 0.02%, respectively. Loaded yeast cells were stable during the 4-week storage period. Both carvacrol and thymol showed substantial releases of around 60% during the first hour and around 70% during the second hour at two different water temperatures, followed by steady release. CONCLUSION: Zateria multiflora boiss essential oil can be encapsulated effectively in S. cerevisiae yeast cells, refrigerated without degradation, and released efficiently. Zateria multiflora boiss essential oil encapsulated into S. cerevisiae yeast may be used as a potential preservative for the food and drug industry. © 2020 Society of Chemical Industry.

Non-antibiotic adjunctive therapy: A promising approach to fight tuberculosis.

Tuberculosis (TB) is currently a clinical and public health problem. There is a concern about the emergence and development of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) species. Additionally, the lack of effective vaccines is another limitation to control the related infections. To overcome these problems various approaches have been pursued such as finding novel drug candidates with a new mechanism of action or repurposing conventional antibiotics. However, these strategies are still far from clinical application. Hence, the use of adjunctive therapy has been suggested for TB. In this paper, we review non-antibiotic adjunctive treatment options for TB. Natural products, vitamins, micronutrients, and trace elementals, as well as non-antibiotic drugs, are examples of agents which have been used as adjunctive therapies. The use of these adjunctive therapies has been shown to improve disease outcomes and reduce the adverse effects of antibiotic drugs. Employing these agents, either alone or in combination with antibiotics, might be considered as a promising approach to control TB infections and achieve better clinical outcomes. However, supportive evidence from randomized controlled trials is still scant and merits further investigations.

Cardiogenic effects of characterized Geum urbanum extracts on adipose-derived human mesenchymal stem cells.

Stem cell therapy is considered as a promising treatment for cardiovascular diseases. Adipose-derived mesenchymal stem cells (ADMSCs) have the ability to undergo cardiomyogenesis. Medicinal plants are effective and safe candidates for cell differentiation. Therefore, the aim of our study was to investigate cardiogenic effects of characterized (HPLC-UV) extracts of Geum urbanum on ADMSCs of adipose tissue. The methanolic extracts of the root and aerial parts of G. urbanum were obtained and MTT assay was used for studying their cytotoxic effects. Then, cells were treated with 50 or 100 µg/mL of the extracts from root and aerial parts of G. urbanum. MTT assay showed that the extracts of G. urbanum did not have any toxic effects on ADMSCs. Immunostaining results showed increase in the expression of α-actinin and cardiac troponin I (cTnI), and quantitative real-time reverse-transcription PCR data confirmed the upregulation of ACTN, ACTC1, and TNNI3 genes in ADMSCs after treatment. According to HPLC fingerprinting, some cardiogenic effects of G. urbanum extracts are probably due to ellagic and gallic acid derivatives. Our findings indicated that G. urbanum extracts effectively upregulated some essential cardiogenic markers, which confirmed the therapeutic role of this plant as a traditional cardiac medicine.

Standardized Sophora pachycarpa Root Extract Enhances Osteogenic Differentiation in Adipose-derived Human Mesenchymal Stem Cells.

Bone defect is an important topic in public health. Novel therapies are based on osteogenic induction by natural antiosteoporotic compounds including plant-derived estrogens. In the current study, the osteogenic potential of Sophora pachycarpa root extract (SPRE) was explored on human adipose-derived mesenchymal stem cells. Herein, adipose-derived mesenchymal stem cells were osteoinducted in the presence of increased concentrations of the extract for 21 days. Then, cell viability was evaluated by MTT assay, and the differentiated cells were stained by Alizarin Red S for calcium deposition and subjected to alkaline phosphatase (ALP) assay for enzymatic activity. To assess the expression of bone-related genes, treated cells were evaluated by real-time polymerase chain reaction. The MTT test demonstrated that SPRE had no toxic effects on the cell viability. Treating the cells with SPRE noticeably promoted ALP activity, mineralization, and mRNA expression of runt-related transcription factor 2 (RUNX2), bone gamma-carboxyglutamate protein (BGLAP), secreted phosphoprotein 1 (SPP1), and collagen type I alpha 1 (COL1A1). Additionally, cells subjected to 0.1 µg/mL SPRE showed the highest osteogenic effects. According to high-performance liquid chromatography fingerprinting of SPRE, the osteoprotective effects of SPRE is probably due to presence of phytochemicals with estrogen-like activity in the extract. Thus, SPRE might be a suitable therapeutic agent for bone defects therapy in the future research. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of Catechins, Green tea Extract and Methylxanthines in Combination with Gentamicin Against Staphylococcus aureus and Pseudomonas aeruginosa: - Combination therapy against resistant bacteria.

OBJECTIVES: Bacterial resistant infections have become a global health challenge and threaten the society's health. Thus, an urgent need exists to find ways to combat resistant pathogens. One promising approach to overcoming bacterial resistance is the use of herbal products. Green tea catechins, the major green tea polyphenols, show antimicrobial activity against resistant pathogens. The present study aimed to investigate the effect of catechins, green tea extract, and methylxanthines in combination with gentamicin against standard and clinical isolates of Staphylococcus aureus (S. aureus) and the standard strain of Pseudomonas aeruginosa (P. aeruginosa). METHODS: The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) values of different agents against bacterial strains were determined. The interactions of green tea extract, epigallate catechin, epigallocatechin gallate, two types of methylxanthine, caffeine, and theophylline with gentamicin were studied in vitro by using a checkerboard method and calculating the fraction inhibitory concentration index (FICI). RESULTS: The MICs of gentamicin against bacterial strains were in the range of 0.312 - 320 µg/mL. The MIC values of both types of catechins were 62.5 - 250 µg/ mL. Green tea extract showed insufficient antibacterial activity when used alone. Methylxanthines had no intrinsic inhibitory activity against any of the bacterial strains tested. When green tea extract and catechins were combined with gentamicin, the MIC values of gentamicin against the standard strains and a clinical isolate were reduced, and synergistic activities were observed (FICI < 1). A combination of caffeine with gentamicin did not alter the MIC values of gentamicin. CONCLUSION: The results of the present study revealed that green tea extract and catechins potentiated the antimicrobial action of gentamicin against some clinical isolates of S. aureus and standard P. aeruginosa strains. Therefore, combinations of gentamicin with these natural compounds might be a promising approach to combat microbial resistance.

Investigation of optimal extraction, antioxidant, and antimicrobial activities of Achillea biebersteinii and A. wilhelmsii.

OBJECTIVE: Achillea species are endowed with multiple biological activities including antioxidant properties. However, no study has yet investigated the impact of extraction method and pH on the biological activities of these plants. The present study aimed to investigate the antioxidant and antimicrobial effects of methanol extracts from the aerial parts of the species Achillea biebersteinii Afan and Achillea wilhelmsii C. Koch (Asteraceae). In addition, the impact of extraction method and pH on these biological activities was evaluated. MATERIALS AND METHODS: Methanol extracts of A. biebersteinii and A. wilhelmsii were prepared using classical maceration and high-intensity ultrasound methods. Ultrasound-assisted extraction was performed at three different pH values: 5.7, 6.3 and 6.9. RESULTS: Total phenolic compounds (range: 20.16-108.54 vs. 17.18-59.61 mg gallic acid equivalent/g sample in A. biebersteinii and A. wilhelmsii, respectively), total flavonoids (range: 8.33-12.97 vs. 7.79-9.41 mg catechin equivalent/g sample), 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity (IC50: 40.63-346.34 vs. 84.02-462.41) and reducing power (IC50: 504.44-4406.67 vs. 1710.00-5501.67) were significantly higher in A. biebersteinii vs. A. wilhelmsii and ultrasound-assisted vs. classical maceration extracts of both species. The aforementioned items were higher at pH = 6.3, followed by pHs of 6.9 and 5.7, respectively. Overall, A. biebersteinii extracts were more active against all of the tested microorganisms than A. wilhelmsii. Sensitivities of Gram-positive bacteria were higher for both Achillea extracts than the Gram-negative bacteria. No observable inhibitory activity was found from different extracts against Aspergillus niger. CONCLUSION: The findings of the present study suggest that methanol extracts of A. biebersteinii and A. wilhelmsii possess antioxidant and antimicrobial activity, being higher in the former. Ultrasound-assisted extraction and pH of 6.3 have significant augmenting impact on the total phenolic and flavonoid content as well as antioxidant activities of both species.