Luteolin Attenuates Airway Mucus Overproduction via Inhibition of the GABAergic System

Abstract

Airway mucus overproduction is one of the most common symptoms of asthma that causes severe clinical outcomes in patients. Despite the effectiveness of general asthma therapies, specific treatments that prevent mucus overproduction in asthma patients remain lacking. Recent studies have found that activation of GABAA receptors (GABAAR) is important for promoting mucus oversecretion in lung airway epithelia. Here, we report that luteolin, a natural flavonoid compound, suppresses mucus overproduction by functionally inhibiting the GABAergic system. This hypothesis was investigated by testing the effects of luteolin on goblet cell hyperplasia, excessive mucus secretion, and GABAergic transmission using histological and electrophysiological approaches. Our results showed that 10 mg/kg luteolin significantly decreased the number of goblet cells in the lung tissue and inhibited mucus overproduction in an in vivo asthma model induced by ovalbumin (OVA) in mice. Patch-clamp recordings showed that luteolin inhibited GABAAR-mediated currents in A549 cells. Furthermore, the inhibitory effects of luteolin on OVA-induced goblet cell hyperplasia and mucus overproduction were occluded by the GABAAR antagonist picrotoxin. In conclusion, our observations indicate that luteolin effectively attenuates mucus overproduction at least partially by inhibiting GABAARs, suggesting the potential for therapeutic administration of luteolin in the treatment of mucus overproduction in asthma patients.

Protective effect of amygdalin on epithelial–mesenchymal transformation in experimental chronic obstructive pulmonary disease mice

“…In this study, both in vivo and in vitro experiments indicated that amygdalin may help decrease the expression of TGF‐β1 and the phosphorylation of smad2/3, inhibiting the EMT process by the TGF‐β/smad pathway to some extent. We hypothesize that amygdalin may competitively combine with the TGF‐β receptor, affecting the expression of TGF‐β and the phosphorylation levels of smad2 and smad3 (Shen et al, ). In addition, we also found that after intervention with amygdalin, the inflammatory response and lung injury in COPD mice were reduced significantly, indicating a certain anti‐inflammatory effect of amygdalin, but this mechanism needs further study.…”

Luteolin Attenuates Allergic Nasal Inflammation via Inhibition of Interleukin-4 in an Allergic Rhinitis Mouse Model and Peripheral Blood From Human Subjects With Allergic Rhinitis

“…The active component of Perilla frutescens, luteolin, is believed to have anti-allergic, anti-inflammatory, and anti-oxidative effect (Seelinger et al, 2008;Lee et al, 2010Lee et al, , 2015Shen et al, 2016;Jang et al, 2017;Kamei et al, 2017;Kim and Yun, 2017;Nunes et al, 2017). Several possible mechanisms of the anti-allergic effects of luteolin have been proposed by previous studies and these include inhibition of pro-inflammatory cytokines, reduction of IgE production, and reduction of mucin production (Kritas et al, 2013;Lee et al, 2015;Shen et al, 2016;Jang et al, 2017). In the present study, we investigated the effects and mechanism of luteolin in a murine AR model.…”

“…In another study, luteolin reduced cellular infiltration in pulmonary parenchyma and nasal tissue, as well as inflammatory cells in bronchoalveolar lavage fluid in a murine model of allergic asthma and rhinitis (Jang et al, 2017). Shen et al (2016) found that luteolin could attenuate airway mucus overproduction in allergic mice.…”

Network analysis of the pharmacological mechanism of Reduning injection in the treatment of novel coronavirus pneumonia

“…In lipopolysaccharide-induced pneumonia, luteolin reduces apoptosis and inhibits expression of inflammatory cytokines [31]. It also reduces the excessive secretion of mucus in the lung airway epithelium [32]. In addition, luteolin has antiviral properties, which interferes with viral replication in the early stages of influenza A virus infection by inhibiting the expression of its coat protein I complex, thus blocking virus invasion and endocytosis [33].…”