Thymoquinone modulates the expression of sepsis‑related microRNAs in a CLP model

Alkharfy,Khalid M.; Ahmad,Ajaz; Jan,Basit L.; Raish,Mohammad; Rehman,Muneeb U.

doi:10.3892/etm.2022.11322

Thymoquinone modulates the expression of sepsis‑related microRNAs in a CLP model

Authors:
- Khalid M. Alkharfy
- Ajaz Ahmad
- Basit L. Jan
- Mohammad Raish
- Muneeb U. Rehman
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Affiliations: Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia, Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Published online on: April 14, 2022 https://doi.org/10.3892/etm.2022.11322
Article Number: 395
Copyright: © Alkharfy et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].

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Abstract

Sepsis is a clinical syndrome common in critical care settings. In the present study, the therapeutic effect of thymoquinone (TQ) on the expression of sepsis‑related microRNAs (miRNAs/miRs), levels of inflammatory markers, organ dysfunction and mortality were investigated in a cecal ligation and puncture (CLP) rat model. A single dose of TQ (1 mg/kg) was administered to animals 24 h after CLP and the mortality rate was assessed up to 7 days following the induction of sepsis. In addition, blood samples were collected at different time points and the expression levels of miRNAs (i.e. miR‑16, miR‑21, miR‑27a and miR‑34a) were examined, along with the levels of inflammatory cytokines (i.e. TNF‑α, IL‑1α, IL‑2, IL‑6 and IL‑10) and sepsis markers (i.e. C‑reactive protein, endothelial cell‑specific molecule‑1, VEGF, procalcitonin and D‑dimer). Liver, kidney and lung tissues were also collected for further histological examination. Treatment with TQ significantly downregulated the miRNA expression levels, as well as the levels of inflammatory cytokines and early‑stage sepsis biomarkers by 30‑70% at 12‑36 h (P<0.05). Furthermore, CLP model rats treated with TQ exhibited an ~80% increase in survival rate compared with that in the untreated CLP group. In addition, TQ induced the preservation of organ function and structure. In conclusion, the present study demonstrated a promising therapeutic effect of TQ against the sequelae of sepsis.

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