Protective Effects of Licochalcone A Improve Airway Hyper-Responsiveness and Oxidative Stress in a Mouse Model of Asthma

Abstract

Licochalcone A was isolated from Glycyrrhiza uralensis and previously reported to have antitumor and anti-inflammatory effects. Licochalcone A has also been found to inhibit the levels of Th2-associated cytokines in the bronchoalveolar lavage fluid (BALF) of asthmatic mice. However, the molecular mechanism underlying airway inflammation and how licochalcone A regulates oxidative stress in asthmatic mice are elusive. In this study, we investigated whether licochalcone A could attenuate inflammatory and oxidative responses in tracheal epithelial cells, and whether it could ameliorate oxidative stress and airway inflammation in asthmatic mice. Inflammatory human tracheal epithelial (BEAS-2B) cells were treated with licochalcone A to evaluate oxidative responses and inflammatory cytokine levels. In addition, BALB/c mice were sensitized with ovalbumin (OVA) and injected intraperitoneally with licochalcone A (5 or 10 mg/kg). Licochalcone A significantly inhibited reactive oxygen species, eotaxin, and proinflammatory cytokines in BEAS-2B cells. Licochalcone A also decreased intercellular adhesion molecule 1 levels in inflammatory BEAS-2B cells, blocking monocyte cell adherence. We also found that licochalcone A significantly decreased oxidative responses, reduced malondialdehyde levels, and increased glutathione levels in the lungs of OVA-sensitized mice. Furthermore, licochalcone A decreased airway hyper-responsiveness, eosinophil infiltration, and Th2 cytokine production in the BALF. These findings suggest that licochalcone A alleviates oxidative stress, inflammation, and pathological changes by inhibiting Th2-associated cytokines in asthmatic mice and human tracheal epithelial cells. Thus, licochalcone A demonstrated therapeutic potential for improving asthma.

Sesamol Alleviates Airway Hyperresponsiveness and Oxidative Stress in Asthmatic Mice

“…Next, mice inhaled 2% OVA administered with an ultrasonic nebulizer for 30 min to induce asthma symptoms (DeVilbiss Pulmo-Aide 5650D, United States) on days 14, 17, 20, 23, and 27. Then, for 2 weeks (days [14][15][16][17][18][19][20][21][22][23][24][25][26][27], in addition to their regular diet, each mouse group received a daily dose of saline (N and OVA groups), sesamol (S10 and S30 groups), or prednisolone (P group). On day 28, we calculated the AHR in all mice; then, on day 29, we sacrificed mice to investigate the asthma pathology, immune regulation, inflammation, and oxidative stress.…”

“…Then, the lung tissue sections were stained with a hematoxylin and eosin (HE) solution to calculate eosinophil infiltration (pathological scores), based on a five-point grading system described previously [16]. Briefly, the pathological degree of eosinophil infiltration was scored as follows: 0, no cell; 1, a few cells; 2, a ring of inflammatory cells one cell layer; 3, a ring of inflammatory cells two to four cells layer; and 4, a ring of inflammatory cells > four cells layer [17]. Lung sections were also stained with a periodic acid-Schiff (PAS) solution (Sigma) to evaluate goblet cell hyperplasia in the trachea and bronchial epithelium, as described previously [17].…”

“…We analyzed the supernatants of cell cultures and BALF from mice with commercial ELISA kits (R&D Systems, Minneapolis, MN), according to the manufacturer's instructions. We determined the levels of IL-6, tumor necrosis factor-α (TNF-α), IL-4, IL-5, IL-8, IL-13, intercellular adhesion molecule 1 (ICAM-1), monocyte chemoattractant protein-1(MCP-1), chemokine (C-C motif) ligand 24 (CCL24), CCL11, and CCL5, as previously described [17]. Furthermore, we used a specific ELISA kit (BD Biosciences, San Diego, CA) to determine serum OVA-specific immunoglobulin (Ig) E, IgG1, and IgG2a levels.…”

“…Malondialdehyde (MDA) activity in the lung was examined with a lipid peroxidation assay kit (Sigma), as described previously [17]. Briefly, lung tissues were homogenized and centrifuged, and the supernatants were isolated.…”

“…The glutathione (GSH) levels in lung tissues were examined with a glutathione assay kit (Sigma), as described previously [17]. Briefly, lung tissues were homogenized in 5% 5-sulfosalicylic acid in a homogenizer (FastPrep-24, MP Biomedicals, Santa Ana, CA, USA).…”