Quercetin reduces inflammatory responses in LPS-stimulated cardiomyoblasts.
Flavonoids possess several biological and pharmacological activities. Quercetin (Q), a naturally occurring flavonoid, has been shown to downregulate inflammatory responses and provide cardioprotection. However, the mechanisms behind the anti-inflammatory properties of Q in cardiac cells are poorly understood. In inflammation, nitric oxide (NO) acts as a proinflammatory mediator and is synthesized by inducible nitric oxide synthase (iNOS) in response to pro-inflammatory agents such as lipopolysaccharide (LPS), a causative agent in myocardial depression during sepsis. In the present study, we evaluated the protective effect of Q on rat cardiac dysfunction during sepsis induced by LPS. Pretreatment of H9c2 cardiomyoblasts with Q inhibited LPS-induced iNOS expression and NO production and counteracted oxidative stress caused by the unregulated NO production that leads to the generation of peroxynitrite and other reactive nitrogen species. In addition, Q pretreatment significantly counteracted apoptosis cell death as measured by immunoblotting of the cleaved caspase 3 and caspase 3 activity. Q also inhibited the LPS-induced phosphorylation of the stress-activated protein kinases (JNK/SAPK) and p38 MAP kinase that are involved in the inhibition of cell growth as well as the induction of apoptosis. In conclusion, these results suggest that Q might serve as a valuable protective agent in cardiovascular inflammatory diseases.
Department of Biochemistry G. Moruzzi, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
Cristina
C
Angeloni
Silvana
S
Hrelia
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D030421:Peroxynitrous Acid / Q000378:metabolism; D011794:Quercetin / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D026361:Reactive Nitrogen Species / Q000378:metabolism; D018805:Sepsis / Q000209:etiology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D026361:Reactive Nitrogen Species; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; D011794:Quercetin; D052247:Nitric Oxide Synthase Type II; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3