Isoliquiritigenin Inhibits Cigarette Smoke-Induced COPD by Attenuating Inflammation and Oxidative Stress via the Regulation of the Nrf2 and NF-κB Signaling Pathways

Abstract

Chronic obstructive pulmonary disease (COPD) is the major leading cause of disease with high-mortality worldwide. Cigarette smoke (CS) is a major factor for COPD. CS causes chronic inflammation and oxidative stress, which contributes to lung dysfunction in COPD. Isoliquiritigenin (ILG), a natural flavonoid derived from the root of liquorice, has been reported to possess antiinflammatory and antioxidant activity. In the present study, we tested the mechanism and protective effects of ILG on CS-induced COPD. Mice were exposed to CS for 2 h twice a day for 4 weeks. ILG was given orally 1 h before CS exposure twice a day for 4 weeks. The bronchial alveolar lavage fluid was collected to test the levels of inflammatory cytokines and the number of inflammatory cells. The lung tissues were obtained to evaluate the pathological changes, lung edema, myeloperoxidase (MPO) activity, malondialdehyde (MDA) level, as well as the expression of the nuclear factor-erythroid 2 (Nrf2) and nuclear factor κB (NF-κB) signaling pathways. The results showed that ILG reduced the infiltration of inflammatory cells and the production of inflammatory cytokines. ILG also reversed CS-induced lung pathological injuries, wet/dry ratio, MPO activity, and MDA level. Further research also showed that ILG dose-dependently up-regulated the expression of Nrf2 and down-regulated the expression of NF-κB signaling pathways induced by CS. In conclusion, ILG protected against CS-induced COPD by inhibiting inflammatory and oxidative stress via the regulation of the Nrf2 and NF-κB signaling pathways.

<p>Development of an Orally Bioavailable Isoliquiritigenin Self-Nanoemulsifying Drug Delivery System to Effectively Treat Ovalbumin-Induced Asthma</p>

“…Even if 7,4ʹ-DHF showed a bit lower IC50 on eotaxin-1 inhibition than that of ILQ, we chose the ILQ as our model drug in the present study. 10 Isoliquiritigenin, a flavonoid compound mainly found in the root of Glycyrrhiza uralensis, had potent antioxidant, 14 anti-inflammatory, [15][16][17] antitumor 18 and antianaphylaxis 10 effects. With a chalcone-type structure, ILQ is easily soluble in several organic solvents and dilute alkaline aqueous solution, but insoluble in water.…”

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

“…On account of the protective effect on the respiratory system against oxidative lung and airway diseases, Nrf2 could reportedly be an attractive therapeutic target for prevention strategies and clinical therapies in respiratory illnesses [ 46 , 47 ]. It has also been reported that isoliquiritigenin was able to attenuate CS-Induced COPD in mice by inhibiting oxidative stress via the regulation of the Nrf2 [ 48 ]. HO-1, NQO1, and SOD are the antioxidant genes regulated by Nrf2 binding to antioxidant response elements [ 49 ].…”

Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Ameliorate Airway Inflammation in a Rat Model of chronic obstructive pulmonary disease (COPD)

“…Cigarette smoke activates NF-κβ within one hour of exposure to the lung thus causing in ammatory reactions which increase white blood cell count, lymphocyte count, and granulocyte count (Churg et al, 2003;Flouris et al, 2012). Data from the pre-clinical study showed 4 weeks of CS exposure signi cantly increased p65 and Iκβα in mice lung as compared to control group (Yu et al, 2018). NF-κβ is also required by IL-1β and IL-17A to induce the expression of MUC5B in bronchial epithelial cells that cause goblet hyperplasia in COPD (Fujisawa et al, 2011).…”