Root Extracts From Ononis spinosa Inhibit IL-8 Release via Interactions With Toll-Like Receptor 4 and Lipopolysaccharide

Extracts from the roots of Ononis spinosa L. (restharrow roots) are traditionally used for the treatment of patients with urinary tract infections due to its mild diuretic activity, caused by the inhibition of renal human hyaluronidase-1 by isoflavonoids. Preliminary studies also indicated anti-infl...

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Main Authors: Verena Spiegler, Barbara Gierlikowska, Thorsten Saenger, John N. Addotey, Jandirk Sendker, Joachim Jose, Anna K. Kiss, Andreas Hensel
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-06-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2020.00889/full
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spelling doaj-dbaca7bb1cdf4f879403a7f22c893d4b2020-11-25T02:39:55ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-06-011110.3389/fphar.2020.00889519045Root Extracts From Ononis spinosa Inhibit IL-8 Release via Interactions With Toll-Like Receptor 4 and LipopolysaccharideVerena Spiegler0Barbara Gierlikowska1Thorsten Saenger2John N. Addotey3Jandirk Sendker4Joachim Jose5Anna K. Kiss6Andreas Hensel7Institute of Pharmaceutical Biology and Phytochemistry, University of Münster, Münster, GermanyDepartment of Laboratory Diagnostics and Clinical Immunology of Developmental Age, Medical University of Warsaw, Warsaw, PolandInstitute of Pharmaceutical and Medicinal Chemistry, University of Münster, Münster, GermanyDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, GhanaInstitute of Pharmaceutical Biology and Phytochemistry, University of Münster, Münster, GermanyInstitute of Pharmaceutical and Medicinal Chemistry, University of Münster, Münster, GermanyDepartment of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Warsaw, PolandInstitute of Pharmaceutical Biology and Phytochemistry, University of Münster, Münster, GermanyExtracts from the roots of Ononis spinosa L. (restharrow roots) are traditionally used for the treatment of patients with urinary tract infections due to its mild diuretic activity, caused by the inhibition of renal human hyaluronidase-1 by isoflavonoids. Preliminary studies also indicated anti-inflammatory effects. The following study aimed at investigating potential anti-inflammatory effects of restharrow extracts, prepared with solvents of different polarity. A dichloromethane extract (OS1), mainly composed of isoflavonoids and triterpenes as characterized by LC-MS, showed a concentration-dependent (25–100 μg/ml) inhibition of IL-8 and TNF-α release from LPS-stimulated human neutrophils. Significant inhibition was also found for the triterpene α-onocerin and the norneolignan clitorienolactone B, isolated from OS1. Further, OS1 and both compounds significantly decreased the expression of the adhesion molecules CD11b/CD18 and conversely increased the expression of CD62L in LPS-stimulated human neutrophils. This finding corresponds to a reduced inflammatory response by the inhibition of adhesion and migration of immune cells. As all of the observed effects are potentially mediated via Toll-like receptor 4 (TLR4) signaling, TLR4 transfected HEK293 cells were incubated with OS1. LPS-induced IL-8 secretion was significantly inhibited in a concentration-dependent manner, confirming TLR4 antagonism. This inhibition, however, was in part caused by an interaction of OS1 with LPS. In addition, also an aqueous extract containing high amounts of isoflavonoid glycosides and saponins from the roots of O. spinosa showed anti-inflammatory effects by interacting with the TLR4 signaling pathway. This study rationalizes the traditional use of extracts from O. spinosa for therapy of urinary tract infections, due to its potential anti-inflammatory effects that are mediated via TLR4 receptor antagonism.https://www.frontiersin.org/article/10.3389/fphar.2020.00889/fullOnonis spinosarestharrow rootinflammationToll-like receptor-4clitorienolactone BCD11b/CD18
collection DOAJ
language English
format Article
sources DOAJ
author Verena Spiegler
Barbara Gierlikowska
Thorsten Saenger
John N. Addotey
Jandirk Sendker
Joachim Jose
Anna K. Kiss
Andreas Hensel
spellingShingle Verena Spiegler
Barbara Gierlikowska
Thorsten Saenger
John N. Addotey
Jandirk Sendker
Joachim Jose
Anna K. Kiss
Andreas Hensel
Root Extracts From Ononis spinosa Inhibit IL-8 Release via Interactions With Toll-Like Receptor 4 and Lipopolysaccharide
Frontiers in Pharmacology
Ononis spinosa
restharrow root
inflammation
Toll-like receptor-4
clitorienolactone B
CD11b/CD18
author_facet Verena Spiegler
Barbara Gierlikowska
Thorsten Saenger
John N. Addotey
Jandirk Sendker
Joachim Jose
Anna K. Kiss
Andreas Hensel
author_sort Verena Spiegler
title Root Extracts From Ononis spinosa Inhibit IL-8 Release via Interactions With Toll-Like Receptor 4 and Lipopolysaccharide
title_short Root Extracts From Ononis spinosa Inhibit IL-8 Release via Interactions With Toll-Like Receptor 4 and Lipopolysaccharide
title_full Root Extracts From Ononis spinosa Inhibit IL-8 Release via Interactions With Toll-Like Receptor 4 and Lipopolysaccharide
title_fullStr Root Extracts From Ononis spinosa Inhibit IL-8 Release via Interactions With Toll-Like Receptor 4 and Lipopolysaccharide
title_full_unstemmed Root Extracts From Ononis spinosa Inhibit IL-8 Release via Interactions With Toll-Like Receptor 4 and Lipopolysaccharide
title_sort root extracts from ononis spinosa inhibit il-8 release via interactions with toll-like receptor 4 and lipopolysaccharide
publisher Frontiers Media S.A.
series Frontiers in Pharmacology
issn 1663-9812
publishDate 2020-06-01
description Extracts from the roots of Ononis spinosa L. (restharrow roots) are traditionally used for the treatment of patients with urinary tract infections due to its mild diuretic activity, caused by the inhibition of renal human hyaluronidase-1 by isoflavonoids. Preliminary studies also indicated anti-inflammatory effects. The following study aimed at investigating potential anti-inflammatory effects of restharrow extracts, prepared with solvents of different polarity. A dichloromethane extract (OS1), mainly composed of isoflavonoids and triterpenes as characterized by LC-MS, showed a concentration-dependent (25–100 μg/ml) inhibition of IL-8 and TNF-α release from LPS-stimulated human neutrophils. Significant inhibition was also found for the triterpene α-onocerin and the norneolignan clitorienolactone B, isolated from OS1. Further, OS1 and both compounds significantly decreased the expression of the adhesion molecules CD11b/CD18 and conversely increased the expression of CD62L in LPS-stimulated human neutrophils. This finding corresponds to a reduced inflammatory response by the inhibition of adhesion and migration of immune cells. As all of the observed effects are potentially mediated via Toll-like receptor 4 (TLR4) signaling, TLR4 transfected HEK293 cells were incubated with OS1. LPS-induced IL-8 secretion was significantly inhibited in a concentration-dependent manner, confirming TLR4 antagonism. This inhibition, however, was in part caused by an interaction of OS1 with LPS. In addition, also an aqueous extract containing high amounts of isoflavonoid glycosides and saponins from the roots of O. spinosa showed anti-inflammatory effects by interacting with the TLR4 signaling pathway. This study rationalizes the traditional use of extracts from O. spinosa for therapy of urinary tract infections, due to its potential anti-inflammatory effects that are mediated via TLR4 receptor antagonism.
topic Ononis spinosa
restharrow root
inflammation
Toll-like receptor-4
clitorienolactone B
CD11b/CD18
url https://www.frontiersin.org/article/10.3389/fphar.2020.00889/full
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