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

TitleTargeting calcium signaling by inositol trisphosphate receptors: A novel mechanism for the anti-asthmatic effects of Houttuynia cordata
Authors
KeywordsAirway remodeling
Asthma
Calcium signaling
Houttuynia cordata
Inositol trisphosphate receptor
Traditional Chinese medicine
Issue Date26-May-2023
PublisherElsevier
Citation
Biomedicine and Pharmacotherapy, 2023, v. 164 How to Cite?
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.


Persistent Identifierhttp://hdl.handle.net/10722/328997
ISSN
2023 Impact Factor: 6.9
2023 SCImago Journal Rankings: 1.493
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorHuang, Alexis Shiying-
dc.contributor.authorTong, Benjamin Chun Kit-
dc.contributor.authorHung, Harry Chun Hin-
dc.contributor.authorWu, Aston Jiaxi-
dc.contributor.authorHo, Olivia Ka Yi-
dc.contributor.authorKong, Anna Hau Yee-
dc.contributor.authorLeung, Maggie Ming Ki-
dc.contributor.authorBai, Jingxuan-
dc.contributor.authorFu, Xiuqiong-
dc.contributor.authorYu, Zhiling-
dc.contributor.authorLi, Min-
dc.contributor.authorLeung, Ting Fan-
dc.contributor.authorMak, Judith Choi Wo-
dc.contributor.authorLeung, George Pak Heng-
dc.contributor.authorCheung, King Ho-
dc.date.accessioned2023-08-05T07:54:30Z-
dc.date.available2023-08-05T07:54:30Z-
dc.date.issued2023-05-26-
dc.identifier.citationBiomedicine and Pharmacotherapy, 2023, v. 164-
dc.identifier.issn0753-3322-
dc.identifier.urihttp://hdl.handle.net/10722/328997-
dc.description.abstract<p>Asthma is a chronic <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/inflammatory-disorder" title="Learn more about inflammatory disease from ScienceDirect's AI-generated Topic Pages">inflammatory disease</a> characterized by airway <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/hypersensitivity" title="Learn more about hypersensitivity from ScienceDirect's AI-generated Topic Pages">hypersensitivity</a> and remodeling. The current <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/therapeutic-procedure" title="Learn more about treatments from ScienceDirect's AI-generated Topic Pages">treatments</a> provide only short-term benefits and may have undesirable side effects; thus, alternative or supplementary therapy is needed. Because <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/intracellular-calcium" title="Learn more about intracellular calcium from ScienceDirect's AI-generated Topic Pages">intracellular calcium</a> (Ca<sup>2+</sup>) signaling plays an essential role in regulating the <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/muscle-contractility" title="Learn more about contractility from ScienceDirect's AI-generated Topic Pages">contractility</a> and remodeling of <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/airway-smooth-muscle-cell" title="Learn more about airway smooth muscle cells from ScienceDirect's AI-generated Topic Pages">airway smooth muscle cells</a>, the targeting of Ca<sup>2+</sup> signaling is a potential therapeutic strategy for asthma. <em><a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/houttuynia-cordata" title="Learn more about Houttuynia cordata from ScienceDirect's AI-generated Topic Pages">Houttuynia cordata</a></em> is a traditional <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/chinese-herbs" title="Learn more about Chinese herb from ScienceDirect's AI-generated Topic Pages">Chinese herb</a> that is used to treat asthma due to its anti-allergic and anti-inflammatory properties. We hypothesized that <em>H. cordata</em> might modulate intracellular Ca<sup>2+</sup> signaling and could help relieve asthmatic <a href="https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/airway-remodeling" title="Learn more about airway remodeling from ScienceDirect's AI-generated Topic Pages">airway remodeling</a>. We found that the mRNA and protein levels of <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/inositol-trisphosphate-receptor" title="Learn more about inositol trisphosphate receptors from ScienceDirect's AI-generated Topic Pages">inositol trisphosphate receptors</a> (IP<sub>3</sub>Rs) were elevated in interleukin-stimulated primary human bronchial <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/smooth-muscle-cell" title="Learn more about smooth muscle cells from ScienceDirect's AI-generated Topic Pages">smooth muscle cells</a> and a house dust mite–sensitized model of asthma. The upregulation of IP<sub>3</sub>R expression enhanced intracellular Ca<sup>2+</sup> release upon stimulation and contributed to airway remodeling in asthma. Intriguingly, pretreatment with <em>H. cordata</em> essential oil rectified the disruption of Ca<sup>2+</sup> signaling, mitigated asthma development, and prevented airway narrowing. Furthermore, our analysis suggested that houttuynin/2-undecanone could be the bioactive component in <em>H. cordata</em> essential oil because we found similar IP<sub>3</sub>R suppression in response to the commercially available derivative sodium houttuyfonate. An <em><a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/in-silico" title="Learn more about in silico from ScienceDirect's AI-generated Topic Pages">in silico</a></em> analysis showed that houttuynin, which downregulates IP<sub>3</sub>R expression, binds to the IP<sub>3</sub> binding domain of IP<sub>3</sub>R and may mediate a direct inhibitory effect. In summary, our findings suggest that <em>H. cordata</em> is a potential alternative treatment choice that may reduce asthma severity by targeting the dysregulation of Ca<sup>2+</sup> signaling.<br></p>-
dc.languageeng-
dc.publisherElsevier-
dc.relation.ispartofBiomedicine and Pharmacotherapy-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectAirway remodeling-
dc.subjectAsthma-
dc.subjectCalcium signaling-
dc.subjectHouttuynia cordata-
dc.subjectInositol trisphosphate receptor-
dc.subjectTraditional Chinese medicine-
dc.titleTargeting calcium signaling by inositol trisphosphate receptors: A novel mechanism for the anti-asthmatic effects of Houttuynia cordata-
dc.typeArticle-
dc.identifier.doi10.1016/j.biopha.2023.114935-
dc.identifier.scopuseid_2-s2.0-85160673547-
dc.identifier.volume164-
dc.identifier.isiWOS:001010800000001-
dc.identifier.issnl0753-3322-

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