scholarly journals Hookworm-derived small molecule extracts suppress pathology in a mouse model of colitis and inhibit secretion of key inflammatory cytokines in primary human leukocytes

2018 ◽  
Author(s):  
Phurpa Wangchuk ◽  
Constantin Constantinoiu ◽  
Konstantinos A. Kouremenos ◽  
Luke Becker ◽  
Linda Jones ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Inflammatory Cytokines ◽  
Small Molecule ◽  
Mononuclear Cells ◽  
Somatic Tissue ◽  
Gas Chromatography Mass Spectrometry ◽  
Human Leukocytes ◽  
Tissue Extracts ◽  
Chromatography Mass Spectrometry ◽  
Anti Inflammatory

ABSTRACTIatrogenic hookworm therapy shows promise for treating disorders that result from a dysregulated immune system, including inflammatory bowel disease (IBD). Here we use a metabolomics approach to characterize the non-protein small molecule complement of hookworms. Gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry analyses of somatic tissue extracts revealed the presence of 52 polar metabolites and 22 non-polar components including short chain fatty acids (SCFA). Several of these small metabolites, notably the SCFA, have been shown to have anti-inflammatory properties in various diseases, including IBD. Using a murine model of colitis and human peripheral blood mononuclear cells, we demonstrate that somatic tissue extracts of the hookworm Ancylostoma caninum contain small molecules with anti-inflammatory activities. Of the five extracts tested, two of them significantly protected mice against T cell-mediated immunopathology and weight loss in a chemically-induced colitis model. Moreover, one of the anti-colitic extracts suppressed ex vivo production of inflammatory cytokines from primary human leukocytes. While the origin of the SCFA (parasite or host microbiota-derived) present in the hookworm somatic tissue extracts cannot be ascertained from this study, it is possible that A. caninum may be actively promoting an anti-inflammatory host microbiome by facilitating immune crosstalk through SCFA production.

scholarly journals Hookworm-Derived Metabolites Suppress Pathology in a Mouse Model of Colitis and Inhibit Secretion of Key Inflammatory Cytokines in Primary Human Leukocytes

2019 ◽  
Vol 87 (4) ◽  
Author(s):  
Phurpa Wangchuk ◽  
Catherine Shepherd ◽  
Constantin Constantinoiu ◽  
Rachael Y. M. Ryan ◽  
Konstantinos A. Kouremenos ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Inflammatory Cytokines ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Clinical Signs ◽  
Gas Chromatography Mass Spectrometry ◽  
Trinitrobenzenesulfonic Acid ◽  
Human Leukocytes ◽  
Polar Metabolites ◽  
Anti Inflammatory

ABSTRACT Iatrogenic hookworm therapy shows promise for treating disorders that result from a dysregulated immune system, including inflammatory bowel disease (IBD). Using a murine model of trinitrobenzenesulfonic acid-induced colitis and human peripheral blood mononuclear cells, we demonstrated that low-molecular-weight metabolites derived from both somatic extracts (LMWM-SE) and excretory-secretory products (LMWM-ESP) of the hookworm, Ancylostoma caninum, display anti-inflammatory properties. Administration to mice of LMWM-ESP as well as sequentially extracted fractions of LMWM-SE using both methanol (SE-MeOH) and hexane-dichloromethane-acetonitrile (SE-HDA) resulted in significant protection against T cell-mediated immunopathology, clinical signs of colitis, and impaired histological colon architecture. To assess bioactivity in human cells, we stimulated primary human leukocytes with lipopolysaccharide in the presence of hookworm extracts and showed that SE-HDA suppressed ex vivo production of inflammatory cytokines. Gas chromatography-mass spectrometry (MS) and liquid chromatography-MS analyses revealed the presence of 46 polar metabolites, 22 fatty acids, and five short-chain fatty acids (SCFAs) in the LMWM-SE fraction and 29 polar metabolites, 13 fatty acids, and six SCFAs in the LMWM-ESP fraction. Several of these small metabolites, notably the SCFAs, have been previously reported to have anti-inflammatory properties in various disease settings, including IBD. This is the first report showing that hookworms secrete small molecules with both ex vivo and in vivo anti-inflammatory bioactivity, and this warrants further exploration as a novel approach to the development of anti-inflammatory drugs inspired by coevolution of gut-dwelling hookworms with their vertebrate hosts.

scholarly journals Comparative Protective Effect of Nigella sativa Oil and Vitis vinifera Seed Oil in an Experimental Model of Isoproterenol-Induced Acute Myocardial Ischemia in Rats

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3221
Author(s):  
Ioana Corina Bocsan ◽  
Raluca Maria Pop ◽  
Octavia Sabin ◽  
Elias Sarkandy ◽  
Paul-Mihai Boarescu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Nigella Sativa ◽  
Ventricular Myocardium ◽  
Grape Seed ◽  
Biological Evaluation ◽  
Gas Chromatography Mass Spectrometry ◽  
Thymol Derivatives ◽  
Chromatography Mass Spectrometry ◽  
Anti Inflammatory

The study’s aim was to characterize the composition of Nigella sativa seed (NSO) and grape seed (GSO) oils, and to evaluate their cardioprotective and anti-inflammatory effect on isoproterenol (ISO)-induced ischemia in rats. Materials and Methods: NSO and GSO supplements were physicochemically characterized. Liquid chromatography–mass spectrometry (HPLC-MS), Fourier-transform infrared spectroscopy (FTIR), and gas chromatography–mass spectrometry (GC-MS) analyses were used to determine the phytochemical composition in the oils. Total polyphenol content (TPC) and in vitro antioxidant activity were also determined. Pretreatment with 4 mL/kg/day NSO or GSO was administered to rats for 14 days. The experimental ischemia was induced by a single administration of ISO 45 mg/kg after 14 days. An electrocardiogram (ECG) was performed initially and 24 h after ISO. Biological evaluation was done at the end of experiment. Results: The HPLC-MS, GC-MS, and FTIR analyses showed that both NSO and GSO are important sources of bioactive compounds, especially catechin and phenolic acids in GSO, while NSO was enriched in flavonoids and thymol derivatives. Pretreatment with GSO and NSO significantly reduced ventricular conduction, prevented the cardiotoxic effect of ISO in ventricular myocardium, and reduced the level of proinflammatory cytokines and CK-Mb. Conclusion: Both NSO and GSO were shown to have an anti-inflammatory and cardioprotective effect in ISO-induced ischemia.

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