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Beneficial Effects of Naringenin in Cigarette Smoke-Induced Damage to the Lung Based on Bioinformatic Prediction and In Vitro Analysis.

Abstract
Naringenin is found mainly in citrus fruits, and is thought to be beneficial in the prevention and control of lung diseases. This study aims to investigate the mechanisms of naringenin against the damage in the lung caused by cigarette smoke. A system bioinformatic approach was proposed to predict the mechanisms of naringenin for protecting lung health. Then, we validated this prediction in BEAS-2B cells treated with cigarette smoke extract (CSE). System bioinformatic analysis indicated that naringenin exhibits protective effects on lung through the inhibition of inflammation and suppression of oxidative stress based on a multi-pathways network, mainly including oxidative stress pathway, Nrf2 pathway, Lung fibrosis pathway, IL-3 signaling pathway, and Aryl hydrocarbon receptor pathway. The in vitro results showed that naringenin significantly attenuated CSE-induced up-regulation of IL-8 and TNF-α. CSE stimulation increased the mRNA expressions of Nrf2, HO-1, and NQO1; the levels of total protein and nuclear protein of Nrf2; and the activity of SOD on days 2 and 4; but decreased these indexes on day 6. Naringenin can balance the antioxidant system by regulating Nrf2 and its downstream genes, preliminarily validating that Nrf2 pathway is involved in the protection offered by naringenin against cigarette smoke-induced damage to the lung. It suggests that dietary naringenin shows possible potential use in the management of lung health.
AuthorsPan Chen, Ziting Xiao, Hao Wu, Yonggang Wang, Weiyang Fan, Weiwei Su, Peibo Li
JournalMolecules (Basel, Switzerland) (Molecules) Vol. 25 Issue 20 (Oct 14 2020) ISSN: 1420-3049 [Electronic] Switzerland
PMID33066647 (Publication Type: Journal Article)
Chemical References
  • CXCL8 protein, human
  • Flavanones
  • Interleukin-8
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • Tumor Necrosis Factor-alpha
  • HMOX1 protein, human
  • Heme Oxygenase-1
  • Superoxide Dismutase
  • NAD(P)H Dehydrogenase (Quinone)
  • NQO1 protein, human
  • naringenin
Topics
  • Cell Line
  • Cell Survival (drug effects)
  • Cigarette Smoking (adverse effects)
  • Computational Biology
  • Epithelial Cells (drug effects)
  • Flavanones (pharmacology)
  • Gene Expression Regulation (drug effects)
  • Gene Ontology
  • Heme Oxygenase-1 (genetics)
  • Humans
  • Interleukin-8 (metabolism)
  • Lung (drug effects, metabolism, pathology)
  • NAD(P)H Dehydrogenase (Quinone) (genetics)
  • NF-E2-Related Factor 2 (genetics, metabolism)
  • Protein Interaction Maps (drug effects, genetics)
  • Superoxide Dismutase (metabolism)
  • Tumor Necrosis Factor-alpha (metabolism)

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