EETs/PPARs activation together mediates the preventive effect of naringenin in high glucose-induced cardiomyocyte hypertrophy.

Abstract

BACKGROUND:

Cardiac hypertrophy is a key pathological process in the context of diabetic cardiomyopathy. Naringenin exhibits multiple pharmacological activities, but the effect of naringenin on cardiomyocyte hypertrophy under diabetic conditions is still far from clear.

METHODS:

Cardiomyocyte hypertrophy was induced by high glucose (HG, glucose at 25.5 mmol/L) in H9c2 cells, which was determined by cell surface area, protein content and atrial natriuretic factor (ANF) mRNA expression. The effect of naringenin on cardiomyocyte hypertrophy was observed and its mechanisms were investigated by administration with various inhibitors on epoxyeicosatrienoic acids (EETs)/peroxisome proliferator-activated receptors (PPARs). The level of 14,15-EET was measured by ELISA. The mRNA and protein expressions were detected by qRT-PCR or Western blot, respectively.

RESULTS:

Naringenin (0.1, 1, 10 μmol/L) inhibited cardiomyocyte hypertrophy in a concentration-dependent manner (P < 0.05), up-regulated the expressions of PPARα, PPARβ, PPARγ and CYP2J3 (P < 0.05), and increased the level of 14,15-EET (P < 0.05). PPOH, a CYP2J3 inhibitor, blocked the naringenin-mediated improvement of myocardial hypertrophy (P < 0.01), and abolished the up-regulation of PPARs expressions (P < 0.01). Meanwhile, MK886, a PPARα antagonist, GSK0660, a PPARβ antagonist, and GW9662, a PPARγ antagonist, reversed the protection of naringenin on cardiomyocytes (P < 0.05), and abrogated the up-regulation of CYP2J3-EET produced by naringenin (P < 0.05).

CONCLUSIONS:

Activation of EETs and PPARs function together may be contributed to the anti-hypertrophic effect of naringenin in H9c2 cells under high glucose condition.

• Authors: Jie Zhang, Hongmei Qiu, Jiajun Huang, Shumei Ding, Bo Huang, Ping Zhou, Qingsong Jiang
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 109 Pg. 1498-1505 (Jan 2019) ISSN: 1950-6007 [Electronic] France
• PMID: 30551401 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Chemical References

• Flavanones
• PPAR gamma
• RNA, Messenger
• Atrial Natriuretic Factor
• naringenin
• Glucose

Topics

• Animals
• Atrial Natriuretic Factor (metabolism)
• Cardiomegaly (chemically induced, drug therapy, metabolism)
• Cell Line
• Diabetic Cardiomyopathies (chemically induced, drug therapy, metabolism)
• Flavanones (pharmacology)
• Glucose (adverse effects)
• Myocytes, Cardiac (drug effects, metabolism)
• PPAR gamma (metabolism)
• RNA, Messenger (metabolism)
• Rats
• Signal Transduction (drug effects)
• Up-Regulation (drug effects)