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1.
Microb Pathog ; 150: 104689, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33307121

ABSTRACT

Annexin A1 (AnxA1) is an anti-inflammatory protein expressed in various cell types, especially macrophages and neutrophils. Because neutrophils play important roles in infections and inflammatory processes and the relationship between AnxA1 and Candida spp. infections is not well-understood, our study examined whether AnxA1 can serve as a target protein for the regulation of the immune response during fungal infections. C57BL/6 wild-type (WT) and AnxA1 knockout (AnxA1-/-) peritoneal neutrophils were coinfected with Candida albicans or Candida auris for 4 h. AnxA1-/- neutrophils exhibited a marked increase in cyclooxygenase 2 (COX-2), phosphorylated extracellular signal-related kinase (ERK), p-38, and c-Jun N-terminal kinase (JNK) levels after coinfection with both Candida spp. A lipidomics approach showed that AnxA1 deficiency produced marked differences in the supernatant lipid profiles of both control neutrophils and neutrophils coinfected with Candida spp. compared with WT cells, especially the levels of glycerophospholipids and glycerolipids. Our results showed that endogenous AnxA1 regulates the neutrophil response under fungal infection conditions, altering lipid membrane organization and metabolism.


Subject(s)
Annexin A1 , Candidiasis , Animals , Annexin A1/genetics , Candida albicans , Candidiasis, Invasive , Mice , Neutrophils
2.
J Enzyme Inhib Med Chem ; 35(1): 42-49, 2020 Dec.
Article in English | MEDLINE | ID: mdl-31656110

ABSTRACT

Matricaria chamomilla L. contains antioxidant flavonoids that can have their bioactivity enhanced by enzymatic hydrolysis of specific glycosyl groups. This study implements an untargeted metabolomics approach based on ultra-performance liquid chromatography coupled with electrospray ionisation quadrupole time-of-flight mass spectrometry technique operating in MSE mode (UPLC-QTOF-MSE) and spectrophotometric analysis of chamomile aqueous infusions, before and after hydrolysis by hesperidinase and ß-galactosidase. Several phenolic compounds were altered in the enzymatically treated infusion, with the majority being flavonoid derivatives of apigenin, esculetin, and quercetin. Although enzymatically modifying the infusion only led to a small increase in antioxidant activity (DPPH• method), its inhibitory effect on pancreatic lipase was of particular interest. The enzymatically treated infusion exhibited a greater inhibitory effect (EC50 of 35.6 µM) than unmodified infusion and kinetic analysis suggested mixed inhibition of pancreatic lipase. These results are of great relevance due to the potential of enzymatically treated functional foods in human health.


Subject(s)
Antioxidants/pharmacology , Enzyme Inhibitors/pharmacology , Flavonoids/pharmacology , Lipase/antagonists & inhibitors , Matricaria/chemistry , Antioxidants/chemistry , Antioxidants/metabolism , Biphenyl Compounds/antagonists & inhibitors , Dose-Response Relationship, Drug , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/metabolism , Flavonoids/chemistry , Flavonoids/metabolism , Glycoside Hydrolases/metabolism , Humans , Hydrolysis , Lipase/metabolism , Matricaria/metabolism , Metabolomics , Molecular Structure , Picrates/antagonists & inhibitors , Structure-Activity Relationship , beta-Galactosidase/metabolism
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