To determine the effect of flavonoids in conjunction with antibiotics in methicillin resistant Staphylococcus aureus (MRSA) a study was designed. The flavonoids included Rutin, Morin, Qurecetin while antibiotics included ampicillin, amoxicillin, cefixime, ceftriaxone, vancomycin, methicillin, cephradine, erythromycin, imipenem, sulphamethoxazole/trimethoprim, ciprofloxacin and levolfloxacin. Test antibiotics were mostly found resistant with only Imipenem and Erythromycin found to be sensitive against 100 MRSA clinical isolates and S. aureus (ATCC 43300). The flavonoids were tested alone and also in different combinations with selected antibiotics. Antibiotics and flavonoids sensitivity assays were carried using disk diffusion method. The combinations found to be effective were sifted through MIC assays by broth macro dilution method. Exact MICs were determined using an incremental increase approach. Fractional inhibitory concentration indices (FICI) were determined to evaluate relationship between antibiotics and flavonoids is synergistic or additive. Potassium release was measured to determine the effect of antibiotic-flavonoids combinations on the cytoplasmic membrane of test bacteria. Antibiotic and flavonoids screening assays indicated activity of flavanoids against test bacteria. The inhibitory zones increased when test flavonoids were combined with antibiotics facing resistance. MICs of test antibiotics and flavonoids reduced when they were combined. Quercetin was the most effective flavonoid (MIC 260 μg/ml) while morin + rutin + quercetin combination proved most efficient with MIC of 280 + 280 + 140 μg/ml. Quercetin + morin + rutin with amoxicillin, ampicillin, cephradine, ceftriaxone, imipenem, and methicillin showed synergism, while additive relationship was indicated between morin + rutin and amoxicillin, cephradine, ceftriaxone, imipenem, and methicillin. Quercetin alone had an additive effect with ampicillin, cephradine, ceftriaxone, imipenem, and methicillin. Potassium leakage was highest for morin + rutin + quercetin that improved further in combination with imipenem. Morin and rutin alone had no activity but in combination showed activity against test bacteria. The flavonoids when used in combination with antibiotics were found to increase each other activity against test bacteria. The relationship between the flavonoids and antibiotics in most of the cases was additive. However in a few cases synergism was also observed. Flavonoids alone or in combinations also damaged bacterial cell membrane.

Background: Berberine is an isoquinoline alkaloid widely used in Ayurveda and traditional Chinese medicine to treat illnesses such as hypertension and inflammatory conditions, and as an anticancer and hepato-protective agent. Berberine has low oral bioavailability due to poor aqueous solubility and insufficient dissolution rate, which can reduce the efficacy of drugs taken orally. In this study, evaporative precipitation of nanosuspension (EPN) and anti-solvent precipitation with a syringe pump (APSP) were used to address the problems of solubility, dissolution rate and bioavailability of berberine. Methods: Semi-crystalline nanoparticles (NPs) of 90–110 nm diameter for APSP and 65–75 nm diameter for EPN were prepared and then characterized using differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). Thereafter, drug content solubility and dissolution studies were undertaken. Berberine and its NPs were evaluated for their antibacterial activity. Results: The results indicate that the NPs have significantly increased solubility and dissolution rate due to conversion of the crystalline structure to a semi-crystalline form. Conclusion: Berberine NPs produced by both APSP and EPN methods have shown promising activities against Gram-positive and Gram-negative bacteria, and yeasts, with NPs prepared through the EPN method showing superior results compared to those made with the APSP method and the unprocessed drug.

Antibiotic resistance (AR) is the result of microbes’ natural evolution to withstand the action of antibiotics used against them. AR is rising to a high level across the globe, and novel resistant strains are emerging and spreading very fast. Acinetobacter baumannii is a multidrug resistant Gram-negative bacteria, responsible for causing severe nosocomial infections that are treated with several broad spectrum antibiotics: carbapenems, β-lactam, aminoglycosides, tetracycline, gentamicin, impanel, piperacillin, and amikacin. The A. baumannii genome is superplastic to acquire new resistant mechanisms and, as there is no vaccine in the development process for this pathogen, the situation is more worrisome. This study was conducted to identify protective antigens from the core genome of the pathogen. Genomic data of fully sequenced strains of A. baumannii were retrieved from the national center for biotechnological information (NCBI) database and subjected to various genomics, immunoinformatics, proteomics, and biophysical analyses to identify potential vaccine antigens against A. baumannii. By doing so, four outer membrane proteins were prioritized: TonB-dependent siderphore receptor, OmpA family protein, type IV pilus biogenesis stability protein, and OprD family outer membrane porin. Immuoinformatics predicted B-cell and T-cell epitopes from all four proteins. The antigenic epitopes were linked to design a multi-epitopes vaccine construct using GPGPG linkers and adjuvant cholera toxin B subunit to boost the immune responses. A 3D model of the vaccine construct was built, loop refined, and considered for extensive error examination. Disulfide engineering was performed for the stability of the vaccine construct. Blind docking of the vaccine was conducted with host MHC-I, MHC-II, and toll-like receptors 4 (TLR-4) molecules. Molecular dynamic simulation was carried out to understand the vaccine-receptors dynamics and binding stability, as well as to evaluate the presentation of epitopes to the host immune system. Binding energies estimation was achieved to understand intermolecular interaction energies and validate docking and simulation studies. The results suggested that the designed vaccine construct has high potential to induce protective host immune responses and can be a good vaccine candidate for experimental in vivo and in vitro studies.

The present study was designed to evaluate the effects of flavonoids luteolin (L) and quercetin + luteolin (Q + L) in combination with commonly used antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates and S. aureus (ATCC 43300). Minimum inhibitory concentrations (MICs) of L and Q + L, as well as the MICs of flavonoids in combination with antibiotics were determined and results showed an increased activity of flavonoids with antibiotics. The synergistic, additive, or antagonistic relationships between flavonoids (L and Q + L) and antibiotics were also evaluated, and additive and synergistic effects were observed for some antibiotic + flavonoid combinations. In addition, some combinations were also found to damage the bacterial cytoplasmic membrane, as assessed through potassium leakage assay. The effects of flavonoids and flavonoids + antibiotics on mecA gene mutations were also tested, and no functional variation was detected in the coding region.

Background: Silibinin has gained in importance in the past few decades as a hepatoprotector and is used widely as oral therapy for toxic liver damage, liver cirrhosis, and chronic inflammatory liver diseases, as well as for the treatment of different types of cancers. Unfortunately, it has low aqueous solubility and inadequate dissolution, which results in low oral bioavailability. Materials and methods: In this study, nanoparticles (NPs) of silibinin, which is a hydrophobic drug, were manufactured using two cost-effective methods. Antisolvent precipitation with a syringe pump (APSP) and evaporative precipitation of nanosuspension (EPN) were used. The prepared NPs were characterized using different analytical techniques such as scanning electron microscopy (SEM), fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and X-ray powder diffractometry (XRD) and were sifted for their bioavailability through in vitro dissolution and solubility studies. Moreover, the prepared NPs were evaluated for antimicrobial activity against a battery of bacteria and yeast. Results: DSC and XRD studies indicated that the prepared NPs were amorphous in nature, with more solubility and dissolution compared to the crystalline form of this drug. NPs prepared through the EPN method had better results than those prepared using the APSP method. Antimicrobial activities of the NPs were improved compared to the unprocessed drugs, while having comparable activities to standard antimicrobial drugs. Conclusion: Results indicate that the NPs have significantly increased solubility, dissolution rate, and antimicrobial activities due to the conversion of crystalline structure into amorphous form.