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The impact of Sambucus nigra L. extract on inflammation, oxidative stress and tissue remodeling in a rat model of lipopolysaccharide-induced subacute rhinosinusitis

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Abstract

Rhinosinusitis is a common disorder related to inflammation of paranasal sinuses and nasal cavity mucosa. Herbal medicines could be an option in the treatment of rhinosinusitis due to their anti-inflammatory and anti-oxidative properties. The study aims to investigate the effect of intranasal Sambucus nigra L. subsp. nigra (SN) extract against inflammation, oxidative stress, and tissue remodeling in nasal and sinus mucosa, but also in serum, lungs, and brain, in Wistar rat model of subacute sinonasal inflammation induced by local administration of lipopolysaccharides (LPS), from Escherichia Coli. The cytokines (TNF-α, IL-1β, IL-6) and oxidative stress (malondialdehyde) in nasal mucosa, blood, lungs, and brain were analyzed. In addition, a histopathological examination was performed, and NF-kB, MMP2, MMP9, TIMP1 expressions were also evaluated in nasal mucosa. Both doses of LPS increased the production of cytokines in all the investigated tissues, especially in the nasal mucosa and blood (p < 0.01 and p < 0.05), and stimulated their secretion in the lungs, and partially in the brain. Malondialdehyde increased in all the investigated tissues (p < 0.01 and p < 0.05). In parallel, upregulation of NF-kB and MMP2 expressions with downregulation of TIMP1, particularly at high dose of LPS, was observed. SN extract reduced the local inflammatory response, maintained low levels of IL-6, TNF-α, and IL-1β. In lungs, SN reduced all cytokines levels while in the brain, the protective effect was noticed only on IL-6. Additionally, SN diminished lipid peroxidation and downregulated NF-kB in animals exposed to a low dose of LPS, with increased TIMP1 expression, while in animals treated with a high dose of LPS, SN increased NF-kB, MMP2, and MMP9 levels. In conclusion, SN extract diminished the inflammatory response, reduced generation of reactive oxygen species (ROS) and, influenced MMPs expressions, suggesting the benficial effect of SN extract on tissue remodeling in subacute rhinosinusitis and on systemic inflammatory response.

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Authors and Affiliations

  1. Department of Pediatrics, “Iuliu Hatieganu” University of Medicine and Pharmacy, 400006, Cluj-Napoca, Romania

    C. N. Tiboc Schnell & S. C. Man

  2. Department of Physiology, “Iuliu Hatieganu” University of Medicine and Pharmacy, Clinicilor Street, No. 1-3, 400006, Cluj-Napoca, Romania

    Gabriela Adriana FILIP, N. Decea, R. Moldovan, R. Opris, D. Olteanu & I. Baldea

  3. Faculty of Chemistry and Chemical Engineering, “Babes-Bolyai” University, 400028, Cluj-Napoca, Romania

    B. Moldovan & L. David

  4. Department of Pathology, University of Agricultural Sciences and Veterinary Medicine, 400035, Cluj-Napoca, Romania

    F. Tabaran

  5. Department of Pharmaceutical Botany, Faculty of Pharmacy, Iuliu Hatieganu University of Medicine and Pharmacy, 400337, Cluj-Napoca, Romania

    A. M. Gheldiu

Authors
  1. C. N. Tiboc Schnell
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  2. Gabriela Adriana FILIP
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  3. N. Decea
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  4. R. Moldovan
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  6. S. C. Man
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  7. B. Moldovan
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  8. L. David
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  9. F. Tabaran
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  10. D. Olteanu
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  12. I. Baldea
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Contributions

Conceptualization of the research was made by CNŢS and GAF. The present study was performed under the supervision of Professor GAF., who was also responsible for project administration, the analysis of the results and the writing-review of the manuscript; CNŢS was involved in the methodology of the research, analysis of the results, and writing of the original draft, with support from SCM ND and RM carried out the experiments and contributed to the sample preparation. DO and IB contributed to the study and the analysis of the data. LD and BM were responsible for the preparation and the characterization of the SN fruit extract. F. and RO performed the histopathological analysis. AM Gheldiu performed HPLC analysis and phytochemical evaluation of the extract. All authors approved the final article.

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Correspondence to Gabriela Adriana FILIP.

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Tiboc Schnell, C.N., FILIP, G.A., Decea, N. et al. The impact of Sambucus nigra L. extract on inflammation, oxidative stress and tissue remodeling in a rat model of lipopolysaccharide-induced subacute rhinosinusitis. Inflammopharmacol 29, 753–769 (2021). https://doi.org/10.1007/s10787-021-00805-y

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