Quercetin prophylaxis protects the kidneys by modulating the renin-angiotensin-aldosterone axis under acute hypobaric hypoxic stress.

The study presented here aims at assessing the effects of hypobaric hypoxia on RAAS pathway and its components along with mitigation of anomalies with quercetin prophylaxis. One hour prior to hypobaric hypoxia exposure, male SD rats were orally supplemented with quercetin (50 mg/kg BW) and acetazolamide (50 mg/kg BW) and exposed them to 25,000 ft. (7,620 m) in a simulated environmental chamber for 12 h at 25 ± 2 °C. Different biochemical parameters like renin activity, aldosterone, angiotensin I, ACE 2 were determined in plasma. As a conventional response to low oxygen conditions, oxidative stress parameters (ROS and MDA) were elevated along with suppressed antioxidant system (GPx and catalase) in plasma of rats. Quercetin prophylaxis significantly down regulated the hypoxia induced oxidative stress by reducing plasma ROS & MDA levels with efficient enhancement of antioxidants (GPx and Catalase). Further, hypoxia mediated regulation of renin and ACE 2 proves the outstanding efficacy of quercetin in repudiating altercations in RAAS cascade due to hypobaric hypoxia. Furthermore, differential protein expression of HIF-1α, NFκB, IL-18 and endothelin-1 analyzed by western blotting approves the biochemical outcomes and showed that quercetin significantly aids in the reduction of inflammation under hypoxia. Studies conducted with Surface Plasmon Resonance demonstrated a binding among quercetin and ACE 2 that indicates that this flavonoid might regulate RAAS pathway via ACE 2. Henceforth, the study promotes the prophylaxis of quercetin for the better adaptability under hypobaric hypoxic conditions via modulating the RAAS pathway.

Big data, integrative omics and network biology.

A cell integrates various signals through a network of biomolecules that crosstalk to synergistically regulate the replication, transcription, translation and other metabolic activities of a cell. These networks regulate signal perception and processing that drives biological functions. The biological complexity cannot be fully captured by a single -omics discipline. The holistic study of an organism-in health, perturbation, exposure to environment and disease, is studied under systems biology. The bottom-up molecular approaches (genes, mRNA, protein, metabolite, etc.) have laid the foundation of current biological knowledge covering the horizon from viruses, bacteria, fungi, plants and animals. Yet, these techniques provide a rather myopic view of biology at the molecular level. To understand how the interconnected molecular components are formed and rewired in disease or exposure to environmental stimuli is the holy grail of modern biology. The omics era was heralded by the genomics revolution but advanced sequencing techniques are now also ubiquitous in transcriptomics, proteomics, metabolomics and lipidomics. Multi-omics data analysis and integration techniques are driving the quest for deeper insights into how the different layers of biomolecules talk to each other in diverse contexts.