Yonsei Med J.  2022 Mar;63(3):220-228. 10.3349/ymj.2022.63.3.220.

Luteolin Protects Cardiomyocytes Cells against Lipopolysaccharide-Induced Apoptosis and Inflammatory Damage by Modulating Nlrp3

• Liu Z
• Gao S
• Bu Y
• Zheng X

• KMID: 2526554
• DOI: http://doi.org/10.3349/ymj.2022.63.3.220

Abstract

Purpose
In this article, we aimed to investigate the influences of luteolin on inflammatory injury to cardiomyocytes induced by lipopolysaccharide (LPS).
Materials and Methods
H9c2 cells were pretreated with different concentrations of luteolin (10, 20, and 50 μM) for 12 h and then stimulated with 10 μg/mL LPS or no LPS for 6 h. Cell viability was detected by CCK-8 assay. Cell apoptosis was determined by flow cytometry. QRT-PCR and Western blotting were utilized to examine mRNA and protein levels. ELISA was used to determine the levels of monocyte chemoattractant protein-1, tumor necrosis factor-alpha, interleukin (IL)-6, IL-1β, and IL-18 in cell supernatants among different groups of H9c2 cells. Immunofluorescence was applied to evaluate reactive oxygen species formation in H9c2 cells. M-mode images of echocardiography, the ejection fraction test, fractional shortening test, end-systolic volume test, and end-diastolic volume test of mouse heart function were obtained by ultrasonic electrocardiogram.
Results
Luteolin could alleviate inflammatory damage and inflammatory factor expression among LPS-induced H9c2 cells. Additionally, we found that luteolin decreased LPS-stimulated inflammatory damage in H9c2 cells by down-regulating NOD-like receptor family pyrin domain containing 3 (Nlrp3). Luteolin also improved myocardial function in mice treated with LPS and reduced myocardial relaxation. Luteolin reversed myocardial histological abnormalities in mice and reduced inflammation and cardiomyocyte apoptosis. Additionally, luteolin inhibited oxidative stress-mediated myocardial and systemic tissue damage in mice. Finally, luteolin reduced LPS-induced inflammatory damage in mouse cardiomyocytes by down-regulating Nlrp3.
Conclusion
We found that luteolin could reduce inflammatory damage to cardiomyocytes induced by LPS by down-regulating Nlrp3.

Keyword

Luteolin; lipopolysaccharide; H9c2 cells; Nlrp3