Luteolin Attenuates Airway Mucus Overproduction via Inhibition of the GABAergic System.
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.
Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan.
Mei-Lin
ML
Shen
Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
Chen-Hung
CH
Wang
Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan.
Ching-Huei
CH
Lin
Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.|Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan.
Ning
N
Zhou
Graduate Institute of Chinese Medicine, China Medical University, Taichung, Taiwan.
Shung-Te
ST
Kao
Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.|Translational Medicine Research Center, China Medical University Hospital, Taichung, Taiwan.
Dong Chuan
DC
Wu
D000072283:A549 Cells; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D020397:Goblet Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009093:Mucus; D010047:Ovalbumin / Q000008:administration & dosage; D010852:Picrotoxin / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000188:drug therapy
D018927:Anti-Asthmatic Agents; D058787:GABA-A Receptor Antagonists; D047311:Luteolin; D010047:Ovalbumin; D010852:Picrotoxin; D011963:Receptors, GABA-A