Quercetin and Its Derivative Counteract Palmitate-Dependent Lipotoxicity by Inhibiting Oxidative Stress and Inflammation in Cardiomyocytes

Maria Concetta Granieri, Carmine Rocca, Anna De Bartolo, Immacolata Cristina Nettore, Vittoria Rago, Naomi Romeo, Jessica Ceramella, Annaluisa Mariconda, Paolo Emidio Macchia, Paola Ungaro, Maria Stefania Sinicropi and Tommaso Angelone ()
Additional contact information
Maria Concetta Granieri: Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, Ecology and Earth Science (DiBEST), University of Calabria, 87036 Rende, Italy
Carmine Rocca: Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, Ecology and Earth Science (DiBEST), University of Calabria, 87036 Rende, Italy
Anna De Bartolo: Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, Ecology and Earth Science (DiBEST), University of Calabria, 87036 Rende, Italy
Immacolata Cristina Nettore: Dipartimento di Medicina Clinica e Chirurgia, Scuola di Medicina, Università degli Studi di Napoli Federico II, 80131 Naples, Italy
Vittoria Rago: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
Naomi Romeo: Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, Ecology and Earth Science (DiBEST), University of Calabria, 87036 Rende, Italy
Jessica Ceramella: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
Annaluisa Mariconda: Department of Science, University of Basilicata, Viale dell’Ateneo Lucano 10, 85100 Potenza, Italy
Paolo Emidio Macchia: Dipartimento di Medicina Clinica e Chirurgia, Scuola di Medicina, Università degli Studi di Napoli Federico II, 80131 Naples, Italy
Paola Ungaro: Istituto per l’Endocrinologia e l’Oncologia Sperimentale (IEOS) “Gaetano Salvatore”, Consiglio Nazionale delle Ricerche, 80131 Naples, Italy
Maria Stefania Sinicropi: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
Tommaso Angelone: Laboratory of Cellular and Molecular Cardiovascular Pathophysiology, Department of Biology, Ecology and Earth Science (DiBEST), University of Calabria, 87036 Rende, Italy

IJERPH, 2023, vol. 20, issue 4, 1-18

Abstract: Cardiac lipotoxicity plays an important role in the pathogenesis of obesity-related cardiovascular disease. The flavonoid quercetin (QUE), a nutraceutical compound that is abundant in the “Mediterranean diet”, has been shown to be a potential therapeutic agent in cardiac and metabolic diseases. Here, we investigated the beneficial role of QUE and its derivative Q2, which demonstrates improved bioavailability and chemical stability, in cardiac lipotoxicity. To this end, H9c2 cardiomyocytes were pre-treated with QUE or Q2 and then exposed to palmitate (PA) to recapitulate the cardiac lipotoxicity occurring in obesity. Our results showed that both QUE and Q2 significantly attenuated PA-dependent cell death, although QUE was effective at a lower concentration (50 nM) when compared with Q2 (250 nM). QUE decreased the release of lactate dehydrogenase (LDH), an important indicator of cytotoxicity, and the accumulation of intracellular lipid droplets triggered by PA. On the other hand, QUE protected cardiomyocytes from PA-induced oxidative stress by counteracting the formation of malondialdehyde (MDA) and protein carbonyl groups (which are indicators of lipid peroxidation and protein oxidation, respectively) and intracellular ROS generation, and by improving the enzymatic activities of catalase and superoxide dismutase (SOD). Pre-treatment with QUE also significantly attenuated the inflammatory response induced by PA by reducing the release of key proinflammatory cytokines (IL-1β and TNF-α). Similar to QUE, Q2 (250 nM) also significantly counteracted the PA-provoked increase in intracellular lipid droplets, LDH, and MDA, improving SOD activity and decreasing the release of IL-1β and TNF-α. These results suggest that QUE and Q2 could be considered potential therapeutics for the treatment of the cardiac lipotoxicity that occurs in obesity and metabolic diseases.

Keywords: cardiomyocytes; lipotoxicity; flavonoids; quercetin (search for similar items in EconPapers)
JEL-codes: I I1 I3 Q Q5 (search for similar items in EconPapers)
Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.mdpi.com/1660-4601/20/4/3492/pdf (application/pdf)
https://www.mdpi.com/1660-4601/20/4/3492/ (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:gam:jijerp:v:20:y:2023:i:4:p:3492-:d:1070663

Access Statistics for this article

IJERPH is currently edited by Ms. Jenna Liu

More articles in IJERPH from MDPI
Bibliographic data for series maintained by MDPI Indexing Manager ().