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.
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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
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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.
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Valero, M.S., González, M., Ramón-Gimenez, M. et al. Jasonia glutinosa (L.) DC., a traditional herbal medicine, reduces inflammation, oxidative stress and protects the intestinal barrier in a murine model of colitis. Inflammopharmacol 28, 1717–1734 (2020). https://doi.org/10.1007/s10787-019-00626-0
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DOI: https://doi.org/10.1007/s10787-019-00626-0