Elucidating the effect of levothyroxine and triiodothyronine on methylglyoxal derived stress.

PURPOSE: Methylglyoxal (MG) is the most potent precursor during the formation of the advanced glycation end products (AGEs). MG-dependent glycative stress contributes to pathogenesis of diabetes, age-related disorders, and cancer. There is a great need to study the reduction process of glycative stress for effective management of metabolic disorders. From natural compounds to synthetic drugs, each element contributes to the reduction of glycative stress. Previously, it was established that the lowering of uric acid, low-density lipoprotein cholesterol, and urine albumin excretion rate, as well as reducing total oxidative stress, were all achieved more effectively with a levothyroxine regimen. Still, there is no such study found that supports the MG-dependent glycative stress reduction with thyroid hormone compound. Our study aims to investigate the effects of T3 and T4 on MG-dependent glycative stress. METHODS: The antiglycation effect was assayed through NBT assay, DNPH assay, ELISA, and fluorescence spectrophotometer. The intracellular reduction in reactive oxygen species (ROS) has been estimated through confocal microscopy. RESULTS: The results revealed an effective reduction in the formation of AGEs adducts and intracellular ROS formation. CONCLUSION: The investigation concludes AGEs formation was suppressed using these compounds, although in vivo and rigorous clinical trials are required in order to verify these findings.

Efflux Pump Inhibition-Based Screening and Anti-Infective Evaluation of Punica granatum Against Bacterial Pathogens.

Drug efflux pumps contribute to bacterial multidrug resistance (MDR), reducing antibiotic effectiveness and causing treatment failures. Besides their role in MDR, efflux pumps also assist in the transportation of quorum sensing (QS) signal molecules and increased the tolerance of biofilms. Recently, the search for efflux pump inhibitors from natural sources, including anti-infective plants, has gained attention as a potential therapy against drug-resistant bacteria. In this study, 19 traditional Indian medicinal plants were screened for their efflux pump inhibitory activity against Escherichia coli TGI. The promising extract, i.e., Punica granatum was subsequently fractioned in the solvents of increasing polarity. Among them, at sub-MIC active EPI fraction was PGEF (P. granatum ethyl acetate fraction), further investigated for anti-infective potential against Chromobacterium violaceum 12,472, Pseudomonas aeruginosa PAO1, and Serratia marcescens MTCC 97. PGEF was also evaluated for in vivo efficacy in Caenorhabditis elegans model. Major phytocompounds were analyzed by mass spectroscopic techniques. At respective Sub-MIC, PGEF reduced violacein production by 71.14% in C. violaceum 12,472. Moreover, PGEF inhibited pyocyanin (64.72%), pyoverdine (48.17%), protease (51.35%), and swarming motility (44.82%) of P. aeruginosa PAO1. Furthermore, PGEF reduced the production of prodigiosin and exoprotease by 64.73% and 61.80%, respectively. Similarly, at sub-MIC, PGEF inhibited (≥ 50%) biofilm development in all test pathogens. The key phytocompounds detected in active fraction include 5-hydroxymethylfurfural, trans-p-coumaric acid 4- glucoside, (-)-Epicatechin 3'-O-glucuronide, and ellagic acid. Interestingly, PGEF also demonstrated anti-infective efficacy against the PAO1-infected C. elegans test model and highlighting its therapeutic potential as an anti-infective agent to combat drug-resistant problems.