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Bioactive Constituents of Lamium album L. as Inhibitors of Cytokine Secretion in Human Neutrophils.

ABSTRACT: The traditional role of Lamium album L. (white dead nettle, Lamiaceae) in providing relief from pain in rheumatism as well as vaginal and cervical inflammation was described. The aim of the study was to screen for the anti-inflammatory bioactivity of compounds isolated from aqueous-methanolic extract of Lamium album herb in human neutrophils (PMNs). The effect of the compounds on the inhibition of selected inflammatory markers released by neutrophils, such as cytokines (IL-8, TNF-?), was studied. The molecular masses and the purity of compounds were determined using high-performance liquid chromatography coupled with diode array detection and mass spectrometry (HPLC-DAD-MSⁿ). The level of cytokines production after incubation with the compounds (1?25 µM) was measured by ELISA. Two derivatives of quercetin, not previously described, were isolated in this study. Phenylpropanoids (verbascoside and phlinoside D), as well as iridoids (lamalbid, and shanzhiside methyl ester), and flavonoids revealed to be more significant inhibitors of IL-8 secretion than TNF-?. The compounds at a concentration of 25 µM, except for shanzhiside methyl ester (6), inhibited secretion of IL-8 in the range from 29.1 to 50.0%. In conclusion, L. album might be a valuable source of bioactive compounds and may provide constituents to limit noninfectious inflammation associated with the aforementioned diseases.

SUBMITTER: Czerwinska ME

PROVIDER: S-EPMC6278331 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Bioactive Constituents of Lamium album L. as Inhibitors of Cytokine Secretion in Human Neutrophils.

Czerwińska Monika E ME Świerczewska Anita A Granica Sebastian S

Molecules (Basel, Switzerland) 20181025 11

The traditional role of Lamium album L. (white dead nettle, Lamiaceae) in providing relief from pain in rheumatism as well as vaginal and cervical inflammation was described. The aim of the study was to screen for the anti-inflammatory bioactivity of compounds isolated from aqueous-methanolic extract of Lamium album herb in human neutrophils (PMNs). The effect of the compounds on the inhibition of selected inflammatory markers released by neutrophils, such as cytokines (IL-8, TNF-α ...[more]

PMID: 30366450

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Project description:Interleukin-1β (IL-1β), a major pro-inflammatory cytokine, is a leaderless cytosolic protein whose secretion does not follow the classical endoplasmic reticulum-to-Golgi pathway, and for which a canonical mechanism of secretion remains to be established. Neutrophils are essential players against bacterial and fungi infections. These cells are rapidly and massively recruited from the circulation into infected tissues and, beyond of displaying an impressive arsenal of toxic weapons effective to kill pathogens, are also an important source of IL-1β in infectious conditions. Here, we analyzed if an unconventional secretory autophagy mechanism is involved in the exportation of IL-1β by these cells. Our findings indicated that inhibition of autophagy with 3-methyladenine and Wortmannin markedly reduced IL-1β secretion induced by LPS + ATP, as did the disruption of the autophagic flux with Bafilomycin A1 and E64d. These compounds did not noticeable affect neutrophil viability ruling out that the effects on IL-1β secretion were due to cell death. Furthermore, VPS34IN-1, a specific autophagy inhibitor, was still able to reduce IL-1β secretion when added after it was synthesized. Moreover, siRNA-mediated knockdown of ATG5 markedly reduced IL-1β secretion in neutrophil-differentiated PLB985 cells. Upon LPS + ATP stimulation, IL-1β was incorporated to an autophagic compartment, as was revealed by its colocalization with LC3B by confocal microscopy. Overlapping of IL-1β-LC3B in a vesicular compartment peaked before IL-1β increased in culture supernatants. On the other hand, stimulation of autophagy by cell starvation augmented the colocalization of IL-1β and LC3B and then promoted neutrophil IL-1β secretion. In addition, specific ELISAs indicated that although both IL-1β and pro-IL-1β are released to culture supernatants upon neutrophil stimulation, autophagy only promotes IL-1β secretion. Furthermore, the serine proteases inhibitor AEBSF reduced IL-1β secretion. Moreover, IL-1β could be also found colocalizing with elastase, suggesting both some vesicles containing IL-1β intersect azurophil granules content and that serine proteases also regulate IL-1β secretion. Altogether, our findings indicate that an unconventional autophagy-mediated secretory pathway mediates IL-1β secretion in human neutrophils.

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Bioactive Constituents of Lamium album L. as Inhibitors of Cytokine Secretion in Human Neutrophils.

Publications

Bioactive Constituents of <i>Lamium album</i> L. as Inhibitors of Cytokine Secretion in Human Neutrophils.

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