Anti-inflammatory activity of carvacrol protects the heart from lipopolysaccharide-induced cardiac dysfunction by inhibiting pyroptosis via NLRP3/Caspase1/Gasdermin D signaling axis.

Autor: Joshi S; Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, 781101, Assam, India., Kundu S; Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, 781101, Assam, India., Priya VV; Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, 781101, Assam, India., Kulhari U; Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, 781101, Assam, India., Mugale MN; Toxicology & Experimental Medicine, CSIR- Central Drug Research Institute (CDRI), Lucknow 226 031, India., Sahu BD; Department of Pharmacology & Toxicology, National Institute of Pharmaceutical Education and Research (NIPER)-Guwahati, Changsari, 781101, Assam, India. Electronic address: bidya.sahu@niperguwahati.ac.in.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2023 Jul 01; Vol. 324, pp. 121743. Date of Electronic Publication: 2023 Apr 27.
DOI: 10.1016/j.lfs.2023.121743
Abstrakt: Aims: Lipopolysaccharide (LPS) is a well-known agent to induce septic conditions. Sepsis-induced cardiomyopathy has an overwhelming death rate. Carvacrol (CVL), a monoterpene phenol, has anti-inflammatory and antioxidant properties. This research aimed to investigate the effect of CVL on LPS-induced dysfunction in the heart. In this study, we evaluated the effect of CVL in LPS-stimulated H9c2 cardiomyoblast cells and Balb/C mice.
Main Methods: LPS was used to induce septic conditions in H9c2 cardiomyoblast cells in vitro and in Balb/C mice. A survival study was conducted to assess the survival rate of mice after LPS and/or CVL treatment.
Key Findings: In vitro studies indicated that CVL inhibits reactive oxygen species (ROS) generation and abates pyroptosis mediated by NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in H9c2 cells. In mice, CVL intervention improved the survival rate in septic conditions. The CVL administration markedly improved the echocardiographic parameters and alleviated the LPS-induced reduction in the ejection fraction (%) and fraction shortening (%). The CVL intervention restored the myocardial antioxidants and histopathological alterations and decreased the pro-inflammatory cytokine contents in the heart. Further findings disclosed that CVL reduced the protein levels of NLRP3, apoptosis-associated speck-like protein (ASC), caspase 1, interleukin (IL)-18, IL-1β, and the pyroptosis-indicative protein, gasdermin-D (GSDMD) in the heart. The autophagy-indicative proteins, beclin 1 and p62 in the heart were also restored in the CVL-treated group.
Significance: Altogether, our findings demonstrated that CVL has a beneficial effect and can be a potential molecule against sepsis-induced myocardial dysfunction.
Competing Interests: Declaration of competing interest The authors declare no conflicts of interest.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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