Lactic Acid Bacteria (LAB) and Neuroprotection, What Is New? An Up-To-Date Systematic Review.

BACKGROUND: In recent years, the potential role of probiotics has become prominent in the discoveries of neurotherapy against neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Lactic acid bacteria (LAB) exhibit neuroprotective properties and exert their effects via various mechanisms of actions. This review aimed to evaluate the effects of LAB on neuroprotection reported in the literature. METHODS: A database search on Google Scholar, PubMed, and Science Direct revealed a total of 467 references, of which 25 were included in this review based on inclusion criteria which comprises 7 in vitro, 16 in vivo, and 2 clinical studies. RESULTS: From the studies, LAB treatment alone or in probiotics formulations demonstrated significant neuroprotective activities. In animals and humans, LAB probiotics supplementation has improved memory and cognitive performance mainly via antioxidant and anti-inflammatory pathways. CONCLUSIONS: Despite promising findings, due to limited studies available in the literature, further studies still need to be explored regarding synergistic effects, efficacy, and optimum dosage of LAB oral bacteriotherapy as treatment or prevention against neurodegenerative diseases.

Investigating the Antibacterial Effects of Synthetic Gamma-Lactam Heterocycles on Methicillin-Resistant Staphylococcus aureus Strains and Assessing the Safety and Effectiveness of Lead Compound MFM514.

Methicillin-resistant Staphylococcus aureus (MRSA) continues to be one of the main causes of hospital-acquired infections in all regions of the world, while linezolid is one of the only commercially available oral antibiotics available against this dangerous gram-positive pathogen. In this study, the antibacterial activity from 32 analogues of synthetic gamma-lactam heterocycles against MRSA was determined. Amongst screened analogues for the minimum inhibitory concentration (MIC) assay, compound MFM514 displayed good inhibitory activity with MIC values of 7.8-15.6 µg/mL against 30 MRSA and 12 methicillin-sensitive S. aureus (MSSA) clinical isolates, while cytotoxicity evaluations displayed a mean inhibitory concentration (IC50) value of > 625 µg/mL, displaying a potential to becoming as a lead compound. In subsequent animal studies for MFM514, a single-dose oral acute toxicity test revealed an estimated mean lethal dose (LD50) value of <5000 mg/kg, while in the mice infection test, a mean effective dose (ED50) value of 29.39 mg/kg was obtained via oral administration. These results suggest that gamma-lactam carbon skeleton, particularly MFM514, is highly recommended to be evaluated further as a new safe and efficacious orally delivered antibacterial agent against MRSA.

In Vitro Evaluations and In Vivo Toxicity and Efficacy Studies of MFM501 against MRSA.

Previously we have discovered a synthetically derived pyrrolidone alkaloid, MFM501, exhibiting good inhibitory activity against 53 MRSA and MSSA isolates with low cytotoxicity against three normal cell-lines with IC50 values at >625 µg/ml. Time-kill assay, scanning electron microscopy (SEM) analysis, in vivo oral acute toxicity test, and mice peritonitis model were carried out in this study. In the time-kill study, MFM501 showed a less than 3 log10 decrease in bacterial colony concentration value (CFU/ml) which represented a bacteriostatic action while displaying a time-dependent inhibitory mechanism. Following that, SEM analysis suggested that MFM501 may exert its inhibitory activity via cytoplasmic membrane disruption. Moreover, MFM501 showed no toxicity effect on treated mice at an estimated median acute lethal dose (LD50) value of more than 300 mg/kg and less than 2000 mg/kg. For the efficacy test, a mean effective dose (ED50) of 87.16 mg/kg was obtained via a single dose oral administration. Our data demonstrated that MFM501 has the potential to be developed further as a new, safe, and effective oral-delivered antibacterial agent against MRSA isolates.