Targeting calcium signaling by inositol trisphosphate receptors: A novel mechanism for the anti-asthmatic effects of Houttuynia cordata

Alexis Shiying Huang, Chun Kit Benjamin Tong, Harry Chun Hin Hung, Aston Jiaxi Wu, Ka Yi Olivia Ho, Anna Hau Yee Kong, Ming Ki Maggie Leung, Jingxuan Bai, Xiuqiong Fu, Zhiling Yu, Min Li, Ting Fan Leung, Judith Choi Wo Mak, George Pak Heng Leung, King-Ho Cheung*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

3 Citations (Scopus)
28 Downloads (Pure)

Abstract

Asthma is a chronic inflammatory disease characterized by airway hypersensitivity and remodeling. The current treatments provide only short-term benefits and may have undesirable side effects; thus, alternative or supplementary therapy is needed. Because intracellular calcium (Ca2+) signaling plays an essential role in regulating the contractility and remodeling of airway smooth muscle cells, the targeting of Ca2+ signaling is a potential therapeutic strategy for asthma. Houttuynia cordata is a traditional Chinese herb that is used to treat asthma due to its anti-allergic and anti-inflammatory properties. We hypothesized that H. cordata might modulate intracellular Ca2+ signaling and could help relieve asthmatic airway remodeling. We found that the mRNA and protein levels of inositol trisphosphate receptors (IP3Rs) were elevated in interleukin-stimulated primary human bronchial smooth muscle cells and a house dust mite–sensitized model of asthma. The upregulation of IP3R expression enhanced intracellular Ca2+ release upon stimulation and contributed to airway remodeling in asthma. Intriguingly, pretreatment with H. cordata essential oil rectified the disruption of Ca2+ signaling, mitigated asthma development, and prevented airway narrowing. Furthermore, our analysis suggested that houttuynin/2-undecanone could be the bioactive component in H. cordata essential oil because we found similar IP3R suppression in response to the commercially available derivative sodium houttuyfonate. An in silico analysis showed that houttuynin, which downregulates IP3R expression, binds to the IP3 binding domain of IP3R and may mediate a direct inhibitory effect. In summary, our findings suggest that H. cordata is a potential alternative treatment choice that may reduce asthma severity by targeting the dysregulation of Ca2+ signaling.
Original languageEnglish
Article number114935
Number of pages15
JournalBiomedicine and Pharmacotherapy
Volume164
Early online date26 May 2023
DOIs
Publication statusPublished - Aug 2023

Scopus Subject Areas

  • Medicine(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology

User-Defined Keywords

  • Asthma
  • Calcium signaling
  • Houttuynia cordata
  • airway remodeling
  • inositol trisphosphate receptor
  • traditional Chinese medicine
  • Airway remodeling
  • Inositol trisphosphate receptor
  • Traditional Chinese medicine

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