Biology subjects

Nair, M. G.

Publications and source records attributed to Nair, M. G..

3 recordsLinked to original sources

bioRxiv2021

The edible seaweed Laminaria japonica contains cholesterol analogues that inhibit Lipid Peroxidation and Cyclooxygenase Enzymes

In this study, 5 sterols were isolated and purified from Laminaria japonica, commonly known as edible brown seaweed, and their structures were identified based on detailed chemical methods and spectroscopic analyses. Spectroscopic analyses characterized 5 sterols as 29-Hydroperoxy-stigmasta-5,24(28)-dien-3{beta}-ol, saringosterol (24-vinyl-cholest-5-ene-3{beta},24-diol), 24-methylenecholesterol, fucosterol (stigmasta-5,24-diene-3{beta}-ol), and 24-Hydroperoxy-24-vinyl-cholesterol. The bioactivities of these sterols were tested using lipid peroxidation (LPO) and cyclooxygenase (COX-1 and -2) enzyme inhibitory assays. Fucosterol exhibited the highest COX-1 and -2 enzyme inhibitory activities at 59 and 47%, respectively. Saringosterol, 24-methylenecholesterol and fucosterol showed higher LPO inhibitory activity at >50% than the other compounds. In addition, the results of molecular docking revealed that the 5 sterols were located in different pocket of COX-1 and -2 and fucosterol with tetracyclic skeletons and olefin methine achieved the highest binding energy (-7.85 and -9.02 kcal/mol) through hydrophobic interactions and hydrogen bond. Our results confirm the presence of 5 sterols in L. japonica and its significant anti-inflammatory and antioxidant activity. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=89 SRC="FIGDIR/small/463984v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@16c3f43org.highwire.dtl.DTLVardef@1ad7385org.highwire.dtl.DTLVardef@7b3c4borg.highwire.dtl.DTLVardef@b3675a_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LISterols 29-hydroperoxy-stigmasta-5,24(28)-dien-3{beta}-ol and 24-hydroperoxy-24-vinyl-cholesterol are identified for the first time in L. japonica. C_LIO_LISaringosterol, 24-methylenecholesterol and fucosterol showed strong LPO inhibitory activity. C_LIO_LIFucosterol showed highest binding affinity for COX-1 and -2 enzymes through hydrophobic interactions. C_LI

biochemistry↗

bioRxiv2021

Diet High in Soybean Oil Increases Susceptibility to Colitis in Mice

The current American diet is high in soybean oil (SO), which consists of unsaturated fatty acids, most notably linoleic acid (LA, C18:2 omega-6). While LA is an essential fatty acid that must be obtained from the diet, high LA consumption has been linked to the development of inflammatory bowel disease (IBD) in humans. Here, we show that a high fat diet (HFD) based on soybean oil increases susceptibility to colitis in wild-type and IL10 knockout mice. It causes immune dysfunction, decreases colon and crypt length and increases intestinal epithelial barrier permeability; these effects were not observed in low LA HFDs. The SO diet also disrupts the balance of isoforms encoded by the IBD susceptibility gene Hepatocyte Nuclear Factor 4 (HNF4). Both the SO diet and an LA gavage cause gut dysbiosis: the SO diet increases the abundance of an adherent, invasive Escherichia coli (AIEC), which can use LA as a carbon source, and the LA gavage decreases the beneficial bacteria Lactobacillus murinus. Metabolomic analysis of both host-associated and cultured bacteria shows that SO increases levels of LA and oxylipins while decreasing eicosapentaenoic acid (EPA, C20:5 omega-3) and endocannabinoids. Our results suggest that excess LA, obtained from a diet high in soybean oil, increases susceptibility to colitis by alterations in intestinal HNF4, gut microbiota and bioactive metabolites.

physiology↗

bioRxiv2020

Host protection to intestinal worm infections: the importance of activated and armed innate effector cells at the host parasite interface.

The intestinal roundworm Heligmosomoides bakeri causes chronic infection in susceptible (C57Bl/6) mice; however, repeat (trickle) infection confers immunity and facilitates worm clearance. We previously showed that this acquired immunity is associated with a strong Th2 response, notably the enhanced production of intestinal granulomas. Here we demonstrate that elevated proportions of IgG1-bound eosinophils and macrophages are observed around the developing tissue worms of trickle-infected female C57Bl/6 mice compared to bolus infected animals. Levels of IgG2c, IgA or IgE were not detected in the granulomas. Increased proportions of SiglecF+ and CD206+ cells, but not Ly6G+ and/or NK1.1+ cells, were also found in the granulomas of trickle-infected mice. However, in the natural world rather than the laboratory setting, immune environments are more nuanced. We examined the impact of a mixed immune environment on trickle infection-induced immunity, using a pre-infection with Toxoplasma gondii. The mixed immune environment resulted in fewer and smaller granulomas with a lack of IgG -bound cells as well as reduced proportions of SiglecF+ and CD206+ cells, measured by immunofluorescence and flow cytometry. This was associated with a higher worm burden in the co-infected animals. Our data confirm the importance of intestinal granulomas and parasite-specific antibody for parasite clearance. They highlight why it may be more difficult to clear worms in the field than in the laboratory. AUTHORS SUMMARYDespite decades of research on intestinal parasitic worms, we are still unable to clearly point to why so many people (approximately 1.8 billion) and most livestock/wild animals are infected with these parasites. We have made progress in understanding how the immune system responds to parasitic worms, and how these parasites manipulate our immune system. However, identifying effective clearance mechanisms is complex and context dependent. We have used models of trickle infection (multiple low doses of parasites) and co-infection (two intestinal parasites) to simulate how people/animals get infected in the real world. Using these models, we have confirmed the host/parasite interface (the granuloma) within the intestinal tissue to be key in determining the hosts ability to clear worms. The lack of specific immune cells and antibodies within the granuloma was associated with chronic infection. Our results help explain why intestinal parasitic worms are so prevalent and why it may be difficult to clear worms in natural settings.

immunology↗