Chemically Defined Lactobacillus plantarum Cell-Free Metabolites Demonstrate Cytoprotection in HepG2 Cells through Nrf2-Dependent Mechanism

Abstract

Centering around the concept that metabolites from the gut commensals can exert metabolic health benefits along the gut–liver axis, we tested whether the cell-free global metabolome of probiotic bacteria can exert hepatoprotective benefits against H2O2-induced oxidative stress. Cell-free global metabolites of Lactobacillus plantarum (LPM) were isolated and untargeted metabolomics was performed. The free radical scavenging potentials of LPM were measured. The cytoprotective effects of LPM were tested on HepG2 cells. A total of 66 diverse metabolites were identified in LPM, among which saturated fatty acids, amino acids and dicarboxylic acids were highly enriched. LPM attenuated cell damage, lipid peroxidation and the levels of intracellular cytoprotective enzymes in H2O2-treated cells. LPM also attenuated H2O2-induced increased expressions of TNF-α and IL-6. However, the cytoprotective effects of LPM were diminished in cells that were pretreated with a pharmacological inhibitor of Nrf2. Our data collectively indicate that LPM can significantly attenuate oxidative damage to HepG2 cells. However, the cytoprotective effects of LPM likely depend on an Nrf2-dependent mechanism.

Improved antioxidant activities of spice require enrichment of distinct yet closely-related metabolic pathways

“…Since transition metals can accelerate intracellular free-radical formation cascade by potentiating the Fenton reaction, iron-chelation activity was measured, and to evaluate the potentials of the spices to limit free-radical mediated peroxidation of cellular lipid, lipid peroxidation assay was performed using chicken brain sample obtained from a local slaughterhouse. All assays were performed against appropriate standards as per previously standardized methods that were adapted to a reduced volume suitable for microplates [ [21] , [22] , [23] , [24] , [25] ]. The range of the highest dose of sample for each assay was based on the linear response range for respective standard compounds in the final volume of the reaction mixture.…”