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

• Published in: Molecules (Basel, Switzerland) Switzerland), 2020-10, Vol.25 (20), p.4704
• Main Authors: Chen, Pan, Xiao, Ziting, Wu, Hao, Wang, Yonggang, Fan, Weiyang, Su, Weiwei, Li, Peibo
• Format: Article
• Language: English
• Subjects: Air pollution; Antioxidants; Asthma; Cell growth; Cell Line; Cell Survival - drug effects; Chronic obstructive pulmonary disease; Cigarette smoke; Cigarette Smoking - adverse effects; Cigarettes; Citrus fruits; Computational Biology; Disease prevention; Epithelial Cells - drug effects; Fibrosis; Flavanones - pharmacology; Gene Expression Regulation - drug effects; Gene Ontology; Heme Oxygenase-1 - genetics; Humans; Inflammation; Interleukin 3; Interleukin 8; Interleukin-8 - metabolism; Lung - drug effects; Lung - metabolism; Lung - pathology; Lung cancer; Lung diseases; lung health; mRNA; NAD(P)H Dehydrogenase (Quinone) - genetics; Naringenin; NF-E2-Related Factor 2 - genetics; NF-E2-Related Factor 2 - metabolism; Oxidative stress; Protein expression; Protein Interaction Maps - drug effects; Protein Interaction Maps - genetics; Proteins; Signal transduction; Smoke; Superoxide Dismutase - metabolism; system bioinformatic approach; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-α
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25204704

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.