Antibacterial activity of Lagerstreomia speciosa and its active compound, corosolic acid, enhances cefotaxime inhibitory activity against Staphylococcus aureus.

AIMS: Various epidemiology studies have reported the emergence of Staphylococcus aureus and its methicillin resistance strain causing global health concerns, especially during and post-COVID-19 pandemic. This pathogen presents as a co-infection in patients with COVID-19. In addition, certain virulence factors and resistance to ß-lactam antibiotics, including cefotaxime, have been identified. We aimed to investigate the antibacterial activity of Lagerstreomia speciosa, a medicinal plant with antidiabetic activity, against S. aureus, including the strain resistant to methicillin. Furthermore, we examined whether the extract and one of its bioactive compounds, corosolic acid, can enhance the therapeutic effect of cefotaxime on antibiotic-resistant S. aureus. METHODS AND RESULTS: The minimum inhibitory concentration of each substance was determined using the standard broth microdilution test following the checkerboard dilution. The type of interactions, synergistic, additivity, indifference, or antagonism, were determined using isobolograms analysis and the dose reduction index (DRI). The evaluation of synergy and bactericidal activity of the natural products in combination with cefotaxime was performed using the time-kill kinetic assay. Corosolic acid, L. speciosa leaves extract, and bark extract alone showed antibacterial activity against all tested S. aureus ATCC 33591, S. aureus ATCC 29213, S. aureus ATCC 25923, and clinical isolated S. aureus. Corosolic acid enhanced the antibacterial activity of cefotaxime, showing a synergistic effect and greater DRI of cefotaxime against all tested S. aureus strains. Time-kill kinetic assay showed that corosolic acid has a more profound effect than L. speciosa extracts to potentiate the bactericidal activity of cefotaxime. Whereas L. speciosa leaves and bark extract showed some inhibitory effect on the growth of S. aureus after a single administration. CONCLUSIONS: Lagerstreomia speciosa leaves and bark extract and its active compound, corosolic acid, could be used as a potential anti-Staphylococcus aureus treatment to enhance the therapeutic use of cefotaxime.

Fucoxanthin Potentiates the Bactericidal Activity of Cefotaxime Against Staphylococcus aureus.

The increasing prevalence of antimicrobial resistance (AMR) in Staphylococcus aureus against commonly used antibiotics is a major global health issue. To prevent the emergence of AMR and maintain the desired therapeutic effect, the use of drug combinations in the therapeutic management of infections can be contemplated. This approach allows for the administration of lower antibiotic dosages without compromising the desired therapeutic outcome. Despite the documented antimicrobial activity of fucoxanthin, a widely recognized marine carotenoid, there are a lack of previous reports exploring its potential to enhance the therapeutic effect of antibiotics. The current study aimed to investigate whether fucoxanthin can inhibit S. aureus including the strains resistant to methicillin and to investigate whether fucoxanthin can enhance the therapeutic effect of cefotaxime, a widely prescribed 3rd-generation cephalosporin ß-lactam antibiotic known to exhibit resistance in certain cases. Synergism or additive interactions were determined using checkerboard dilution and isobologram analysis, while bactericidal activity was carried out using the time-kill kinetic assay. It is important to highlight that a synergistic bactericidal effect was observed in all strains of S. aureus when fucoxanthin was combined with cefotaxime at a specific concentration ratio. These findings suggest that fucoxanthin holds promise in enhancing the therapeutic efficacy of cefotaxime.

Synergistic Effect and Time-Kill Evaluation of Eugenol Combined with Cefotaxime Against Staphylococcus aureus.

Eugenol, a clove-derived aromatic compound has shown antibacterial activity against many species, including Staphylococcus aureus. Epidemiology studies from the past two decades reported an increased number of healthcare-associated and skin tissue infections due to S. aureus antimicrobial resistance (AMR) including several cases of resistance to ß-lactam antibiotics, such as cefotaxime. We aimed to investigate whether eugenol can cause lethality of S. aureus including the strain resistant to methicillin and the wild strain isolated from a hospital patient. Moreover, we asked whether eugenol could enhance the therapeutic effect of cefotaxime, one of the most prescribed 3rd generation cephalosporin ß-lactam antibiotics, of which S. aureus resistance to this antibiotic has emerged. The minimum inhibitory concentration (MIC) of each substance was determined using the standard broth microdilution test following the combination experiment performed using checkerboard dilution. The type of interactions, including synergistic and additivity, was determined using isobologram analysis, and the dose reduction index (DRI) was calculated. The time-kill kinetic assay was performed to evaluate the dynamic bactericidal activity of eugenol alone and in combination with cefotaxime. We showed that eugenol alone is bactericidal against S. aureus ATCC 33591 and the clinical isolate. Eugenol combined with cefotaxime resulted synergistic effect against S. aureus ATCC 33591, ATCC 29213, and ATCC 25923. Eugenol may be capable to improve the therapeutic effect of cefotaxime against methicillin-resistant S. aureus (MRSA).

Function of selected natural antidiabetic compounds with potential against cancer via modulation of the PI3K/AKT/mTOR cascade.

Diabetes mellitus (DM) is a metabolic disorder with growing global incidence, as 387 million people were diagnosed in 2014 with an expected projection of 642 million in 2040. Several complications are associated with DM including heart attack, stroke, kidney failure, blindness, and cancer. The latter is the second leading cause of death worldwide accounting for one in every six deaths, with liver, pancreas, and endometrium cancers are the most abundant among patients with diabetes. Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway plays a vital role in developing a wide array of pathological disorders, among them diabetes and cancer. Natural secondary metabolites that counteract the deleterious effects of reactive oxygen species (ROS) and modulate PI3K/Akt/mTOR pathway could be a promising approach in cancer therapy. Here, 717 medicinal plants with antidiabetic activities were highlighted along with 357 bioactive compounds responsible for the antidiabetic activity. Also, 43 individual plant compounds with potential antidiabetic activities against cancer via the modulation of PI3K/Akt/mTOR cascade were identified. Taken together, the available data give an insight of the potential of repurposing medicinal plants and/or the individual secondary metabolites with antidiabetic activities for cancer therapy.