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Jasonia glutinosa (L.) DC., a traditional herbal medicine, reduces inflammation, oxidative stress and protects the intestinal barrier in a murine model of colitis

  • Marta Sofía ValeroEmail author
  • Mateo González
  • Mariano Ramón-Gimenez
  • Paula B. Andrade
  • Eduardo Moreo
  • Francisco Les
  • Fátima Fernandes
  • Carlota Gómez-Rincón
  • César Berzosa
  • José Antonio García de Jalón
  • Mª. Pilar Arruebo
  • Miguel Ángel Plaza
  • Ralf Köhler
  • Víctor LópezEmail author
  • Patricia Valentão
  • Marta Castro
Original Article
  • 28 Downloads

Abstract

Jasonia glutinosa (L.) DC., known as rock tea (RT), is traditionally used in Spain as a digestive due to its beneficial properties in bowel disorders. The pharmacological nature of these properties has not been established yet. The aim of this work was to evaluate the therapeutic utility of RT in experimental colitis and to identify chemical constituents with anti-inflammatory and/or anti-oxidative properties. RT extract was prepared with ethanol in a Soxhlet apparatus and analysed by HPLC–DAD. Superoxide radical scavenging properties, xanthine oxidase and lipoxygenase (5-LOX) inhibitory activity, and capability to lower nitric oxide (NO) and tumor necrosis factor α (TNF-α) levels were measured in cell-free and cell-based assays. In the 2.5%-dextran-sodium sulphate (DSS) injury-repair model of ulcerative colitis (UC), mice were daily treated with sulfasalazine (SSZ, as reference drug, 100 mg/kg bw), RT (5, 25 and 50 mg/kg bw, p.o.), or vehicle over 20 days. Colitis was scored daily. Colon samples were examined macroscopically and histopathologically. Protein levels of myeloperoxidase (MPO), interleukins 6, and 10 (IL-6, IL-10), inducible NO synthase (iNOS), and cyclooxygenase-2 (COX-2) were studied as markers of oxidative stress and inflammatory activity. The integrity of the apical epithelial layer was assessed by immunofluorescence staining of zonula ocludens-1 (ZO-1). Finally, intestinal contractility was also evaluated by isometric myography. Fifteen phenolic compounds and three pigments were identified and quantified, of which caffeoylquinic acids, and the flavonoid, quercetin-3-O-galactoside, were the most abundant. RT extract significantly scavenged superoxide radicals, inhibited 5-LOX activity, and lowered NO and TNF-α levels. DSS-treated mice receiving RT scored clinically lower than controls during the first 3 days of DSS treatment and during the recovery period. SSZ was less effective than RT. Anatomical and histological examination of colon samples revealed that RT significantly prevented colon shortening, increased colon thickness, and lowered the macroscopic damage score. RT also significantly prevented the increase of MPO activity, IL-6 levels, iNOS and COX-2 expression, the loss of ZO-1 apical expression, and normalized contractility disturbances. In conclusion, daily administration of RT showed therapeutic properties in the DSS-model of UC. The benefits of RT can likely be attributed to its anti-inflammatory and antioxidant phenolic and flavonoid constituents.

Keywords

Inflammation Murine Polyphenols Rock tea Ulcerative colitis Ethnopharmacology 

Abbreviations

ACh

Acetylcholine

AUC

Area under the curve

COX-2

Cyclooxygenase-2

CV

Coefficient of variation

DAI

Disease activity index,

DMSO

Dimethyl sulfoxide

DSS

Dextran-sodium sulphate

HE

Haematoxylin–eosin

HPLC–DAD

High-pressure liquid chromatography coupled to a diode-array detector

iNOS

Inducible nitric oxide synthase

IBD

Inflammatory bowel disease

IL-6

Interleukin 6

IL-10

Interleukin 10

LOD

Limit of detection

LOQ

Limit of quantification

5-LOX

5-Lipoxygenase

LPS

Lipopolysaccharide

MPO

Myeloperoxidase

NADH/PMS

Β-Nicotinamide adenine dinucleotide/phenazine methosulfate

NBT

Nitrotetrazolium blue chloride

NO

Nitric oxide

\({\text{O}}_{2}^{ \cdot - }\)

Superoxide radical

RT

Rock tea

SSZ

Sulfasalazine

TNF-α

Tumor necrosis factor-alpha

UC

Ulcerative colitis

X/XO

Xanthine/xanthine oxidase

ZO-1

Zonula occludens-1

Notes

Acknowledgements

This work was supported by the government of Aragón, Spain (E-02 and B61), Universidad de Zaragoza (ref. JIUZ-2018-BIO-09 and BIO-2015-02), National Funds (FCT/MEC, Fundação para a Ciência e a Tecnologia/Ministério da Educação e Ciência) through project UID/QUI/50006/2013, co-financed by European Union (FEDER under the Partnership Agreement PT2020), from Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) (project NORTE-01-0145-FEDER-000024), and from Programa de Cooperación Interreg V-A España – Portugal (POCTEP) 2014-2020 (project 0377_IBERPHENOL_6_E) and the European Social Fund “Construyendo Europa desde Aragón”. The authors also thank the Scientific Services of the Center for Biomedical Investigation (CIBA) for technical assistance. Jose Manuel López Cano is acknowledged for carrying out in vitro experiments with macrophages and Dr. Elisa Langa (USJ) for extraction procedures with the plant material.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

This study was performed in accordance with the European Union Directive 2010/63 EU concerning experimental animal protection. Experimental protocols were approved by the Ethics Committee of the University of Zaragoza (PI66/14, Spain).

Consent for publication

All persons gave their informed consent prior to their inclusion in the study.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Marta Sofía Valero
    • 1
    • 2
    • 3
    Email author
  • Mateo González
    • 4
  • Mariano Ramón-Gimenez
    • 4
  • Paula B. Andrade
    • 5
  • Eduardo Moreo
    • 6
  • Francisco Les
    • 4
  • Fátima Fernandes
    • 5
  • Carlota Gómez-Rincón
    • 4
  • César Berzosa
    • 4
  • José Antonio García de Jalón
    • 7
  • Mª. Pilar Arruebo
    • 1
    • 2
    • 3
  • Miguel Ángel Plaza
    • 1
    • 2
    • 3
  • Ralf Köhler
    • 8
  • Víctor López
    • 3
    • 4
    Email author
  • Patricia Valentão
    • 5
  • Marta Castro
    • 1
    • 2
    • 3
  1. 1.Departamento de Farmacología y FisiologíaUniversidad de ZaragozaSaragossaSpain
  2. 2.Instituto de Investigación Sanitaria Aragón (IIS Aragón)SaragossaSpain
  3. 3.Instituto Agroalimentario de Aragón, IA2Universidad de Zaragoza-CITASaragossaSpain
  4. 4.Facultad de Ciencias de la Salud, Universidad San JorgeVillanueva de GállegoSpain
  5. 5.REQUIMTE/LAQV, Laboratório de Farmacognosia, Departamento de Química, Faculdade de FarmáciaUniversidade do PortoPortoPortugal
  6. 6.Grupo de genética de micobacterias. Dpto. Microbiología, Medicina Preventiva y Salud PúblicaUniversidad de ZaragozaSaragossaSpain
  7. 7.Departamento de Patología AnimalUniversidad de ZaragozaSaragossaSpain
  8. 8.Aragon Agency for Research and Development (ARAID)SaragossaSpain

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