Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Floroindole confers protection against cecal ligation and puncture-induced sepsis via inhibition of NF-kB p65 phosphorylation

Zhiwen Zhou¹, Xiang Ren¹, Aiping Li¹, Wensheng Zhou¹, Li Huang²

¹Department of Neurology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410016; ²Department of Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.

For correspondence:- Li Huang Email: lesueer@yahoo.com Tel:+8673189753999

Accepted: 27 May 2019 Published: 30 June 2019

Citation: Zhou Z, Ren X, Li A, Zhou W, Huang L. Floroindole confers protection against cecal ligation and puncture-induced sepsis via inhibition of NF-kB p65 phosphorylation. Trop J Pharm Res 2019; 18(6):1161-1166 doi: 10.4314/tjpr.v18i6.2

© 2019 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the protective effect of floroindole against cecal ligation and puncture (CLP)-induced sepsis, as well as the underlying mechanism of action.

Methods: Thirty-five 10–week-old male Wistar rats weighing 190 - 210 g (mean: 200.00 ± 10.10 g) were used for this study. The rats were randomly assigned to seven groups of five rats each, viz, normal control group, and six CLP groups. The CLP groups were those subjected to cecal ligation and puncture (CLP). The first 5 CLP groups received 2, 4, 6, 8 or 10 mg/kg floroindole, respectively, 1 h after CLP, via intraperitoneal route (i.p.) while the 6th CLP group served as untreated control. Western blotting, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative polymerase chain reaction (qRT-PCR) were used for the assessment of the expression levels of tumor necrosis factor-α (TNF- α), interleukn-6 (IL-6), nucleotide-binding oligomerization domain 2 (NOD2) and p-NF-κB p65.

Results: Cecal ligation and puncture (CLP) significantly and time-dependently upregulated the expressions of TNF-α, IL-6 and NOD2 in intestinal tissues of rats (p < 0.05). However, treatment with floroindole significantly, and dose-dependently down-regulated CLP-induced expressions of these proteins (p < 0.05). Treatment of rats with floroindole also significantly and dose-dependently inhibited CLP-induced phosphorylation of NF-κB p65 in rat ileum (p < 0.05).

Conclusion: The results obtained in this study demonstrate that floroindole confers some degree of protection against CLP-induced sepsis via inhibition of NF-κB p65 phosphorylation.

Keywords: Sepsis, Cecal ligation, Cytokines, expression, Phosphorylation