Alternatives Therapeutic Approaches to Conventional Antibiotics: Advantages, Limitations and Potential Application in Medicine.

Resistance to antimicrobials and particularly multidrug resistance is one of the greatest challenges in the health system nowadays. The continual increase in the rates of antimicrobial resistance worldwide boosted by the ongoing COVID-19 pandemic poses a major public health threat. Different approaches have been employed to minimize the effect of resistance and control this threat, but the question still lingers as to their safety and efficiency. In this context, new anti-infectious approaches against multidrug resistance are being examined. Use of new antibiotics and their combination with new ß-lactamase inhibitors, phage therapy, antimicrobial peptides, nanoparticles, and antisense antimicrobial therapeutics are considered as one such promising approach for overcoming bacterial resistance. In this review, we provide insights into these emerging alternative therapies that are currently being evaluated and which may be developed in the future to break the progression of antimicrobial resistance. We focus on their advantages and limitations and potential application in medicine. We further highlight the importance of the combination therapy approach, wherein two or more therapies are used in combination in order to more effectively combat infectious disease and increasing access to quality healthcare. These advances could give an alternate solution to overcome antimicrobial drug resistance. We eventually hope to provide useful information for clinicians who are seeking solutions to the problems caused by antimicrobial resistance.

Syzygium aromaticum bud (clove) essential oil is a novel and safe aldose reductase inhibitor: in silico, in vitro, and in vivo evidence.

PURPOSE: This study aimed to evaluate the antioxidant and antidiabetic properties of clove essential oil (CEO) and to elucidate its mode of action, using selected biochemical targets, relevant to diabetes, and, specifically, its inhibitory effect on the polyol pathway. METHODS: In the current study, CEO was examined for its inhibitory effects on aldose reductase in silico, in vitro, and in vivo, as well as its antioxidative activity. RESULTS: In silico docking studies showed that all the selected major compounds of CEO have an energy change ranging between - 5.5 and - 8.8 kcal/mol and an inhibition constant ranging between 357.08 nM and 93.12 µM. CEO significantly inhibits aldose reductase with an IC50 value of 58.55 ± 5.84 µg/mL in a noncompetitive manner. The supplementation of CEO at 20 mg/kg BW decreases retinal sorbitol dehydrogenase activity via decreased aldose reductase activity in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. Moreover, diabetic rats injected with CEO have exhibited improved levels of glycemia. The IC50 values for ABTS, hydroxyl, and hydrogen peroxide scavenging activities of CEO were found to be 34.42, 277.4, and 39.99 µg/mL, respectively. Reducing power assay and phosphomolybdate assay exhibited a reduction force with the A0.5 values of 50.25 and 140.16 µg/mL, respectively. CONCLUSION: CEO potentially exerts a beneficial effect on diabetes-related complications due to its antioxidant and inhibitory effect on aldose reductase activity.

Bioactive Compounds from Ephedra fragilis: Extraction Optimization, Chemical Characterization, Antioxidant and AntiGlycation Activities.

Response surface methodology (RSM) with a Box-Behnken design (BBD) was used to optimize the extraction of bioactive compounds from Ephedra fragilis. The results suggested that extraction with 61.93% ethanol at 44.43 °C for 15.84 h was the best solution for this combination of variables. The crude ethanol extract (CEE) obtained under optimum extraction conditions was sequentially fractionated with solvents of increasing polarity. The content of total phenolic (TP) and total flavonoid (TF) as well as the antioxidant and antiglycation activities were measured. The phytochemical fingerprint profile of the fraction with the highest activity was characterized by using RP-HPLC. The ethyl acetate fraction (EAF) had the highest TP and TF contents and exhibited the most potent antioxidant and antiglycation activities. The Pearson correlation analysis results showed that TP and TF contents were highly significantly correlated with the antioxidant and antiglycation activities. Totally, six compounds were identified in the EAF of E. fragilis, including four phenolic acids and two flavonoids. Additionally, molecular docking analysis also showed the possible connection between identified bioactive compounds and their mechanisms of action. Our results suggest new evidence on the antioxidant and antiglycation activities of E. fragilis bioactive compounds that may be applied in the treatment and prevention of aging and glycation-associated complications.

Antibiotic Resistance Pattern of Extended Spectrum Beta Lactamase Producing Escherichia coli Isolated From Patients With Urinary Tract Infection in Morocco.

Extended-spectrum ß-lactamases producing Escherichia coli (ESBL-EC) lend resistance to most ß-lactam antibiotics. Because of limited treatment options, ESBL-EC infections are generally more difficult to treat, leading to higher hospital costs, reduced rates of microbiological and clinical responses, and a threat to the patient's life. This study aimed to determine the antibiotic resistance pattern of ESBL-EC isolated from patients with urinary tract infection in Morocco. This retrospective laboratory-based study was conducted at Cheikh Khalifa International University Hospital, Casablanca, from January 2016 to June 2019. A total of 670 urine samples were collected from urinary tract infection patients and processed by standard microbiological methods. In vitro susceptibility testing to different antibiotics of all identified isolates of Escherichia coli (E. coli) was performed following Kirby-Bauer's disc diffusion method on Mueller-Hinton Agar according to the EUCAST standards. The reviewing of ESBL-EC was confirmed by the appearance of a characteristically shaped zone referred to as a "champagne cork" using the Combined Disk Test. Among a total of 438 E. coli isolated from nonrepetitive urine samples, two hundred fifty-nine (59%) were ESBL-EC, of which 200 (77%) were isolated from adult patients (over the age of 50) and the majority were female. All ESBL-EC isolates were resistant to third-generation cephalosporin and quinolones and sensitive to carbapenem and fosfomycin. Knowledge of antimicrobial resistance patterns in ESBL-EC, the major pathogen associated with urinary tract infection, is indispensable as a guide in choosing empirical antimicrobial treatment.

Purification and characterization of aldose reductase from jerboa (Jaculus orientalis) and evaluation of its inhibitory activity by Euphorbia regis-jubae (Webb & Berth) extracts.

This study aimed, for the first time, to assess the purification of aldose reductase (AR) in Jaculus orientalis (Dipodidae family) kidney and to evaluate the in vitro aldose reductase inhibitory (ARI) effects of Euphorbia regis-jubae (Euphorbiaceae family) aqueous and hydroethanolic extracts. Initial screening assay of the enzymatic AR activity in different jerboa states (euthermic, prehibernating and hibernating) and tissues (brain, brown adipose tissue, liver and kidneys) was assessed. Then, AR has been purified to homogeneity from the kidneys of prehibernating jerboas by a series of chromatographic technics. Furthermore, the in vitro and in silico ARI effects of E. regis-jubae (Webb & Berth) extracts, characterized by hight performance liquid chromatography (HPLC) on the purified enzyme were evaluated. Our results showed that the highest enzyme activity was detected in the kidneys, followed by white adipose tissue and the lungs of pre-hibernating jerboa. The enzyme was purified to homogeneity from jerboa kidneys during prehibernating state with a purification factor of 53.4-fold and a yield of about 6%. AR is monomeric, active in D(+)-glyceraldehyde substrate and in disodium phosphate buffer. The pH and temperature for AR were determined to be 6.5-7.5 and 35 °C, respectively. Results of the in vitro ARI activity was strongest with both the hydroethanolic extract (IC50 = 96.45 µg/mL) and aqueous extract (IC50 = 140 µg/mL). Molecular docking study indicated that catechin might be the main component in both aqueous and hydroethanolic extracts to inhibited AR. This study provides new evidence on the ARI effect of E. regis-jubae (Webb & Berth), which may be related to its phenolic constituents.

Cytoprotective effect of ethyl acetate fraction from Ephedra fragilis on H2O2-induced oxidative damage in Tetrahymena pyriformis.

The main purpose of the present study was to investigate the ability of ethyl acetate fraction (EAF) from Ephedra fragilis to function as a protective agent against hydrogen peroxide induced oxidative damage in Tetrahymena pyriformis. The cells were preincubated with EAF (50-200 µg/mL) or ascorbic acid (50 µg/mL) for 24 h, followed by incubation with 50% H2O2 inhibitory concentration for 48 h. Cell viability was assessed using trypan exclusion method. Cell morphology and mobility, antioxidant enzymes activities (catalase (CAT), superoxide dismutase (SOD) and glutathione reductase (GR)), malondialdehyde (MDA) and protein carbonyl (PCO) levels, DNA fragmentation and metabolic enzymes activities (succinate dehydrogenase (SDH) and NADPH-cytochrome c reductase (NCCR)) were investigated. Our results indicate that, pretreatment of T. pyriformis cells with EAF improved the cell viability, restored normal cell mobility and morphology, decreased the levels of both MDA and PCO level, prevent DNA fragmentation and enhanced the activity of antioxidant (CAT, SOD and GR) and metabolic (SDH and NCCR) enzymes in H2O2 damaged cells. In conclusion, these results suggest for the first time that E. fragilis is a promising source of natural antioxidants, that could offer protection against oxidative stress and should be further exploited for its use in clinical medicine.