In-vitro and in-vivo anti-allergic effects of magnolol on allergic rhinitis via inhibition of ORAI1 and ANO1 channels (2025)

Phan, H. T. L., Nam, Y. R., Kim, H. J., Woo, J. H., NamKung, W., Nam, J. H. (2022). In-vitro and in-vivo anti-allergic effects of magnolol on allergic rhinitis via inhibition of ORAI1 and ANO1 channels. Journal of Ethnopharmacology, 289, Article 115061. https://doi.org/10.1016/j.jep.2022.115061

Phan, Hong Thi Lam ; Nam, Yu Ran ; Kim, Hyun Jong et al. / In-vitro and in-vivo anti-allergic effects of magnolol on allergic rhinitis via inhibition of ORAI1 and ANO1 channels. In: Journal of Ethnopharmacology. 2022 ; Vol. 289.

@article{05801bd9cdf148fd910c3cf9ab09f1f3,

title = "In-vitro and in-vivo anti-allergic effects of magnolol on allergic rhinitis via inhibition of ORAI1 and ANO1 channels",

abstract = "Ethnopharmacological relevance: Flos Magnoliae (the dried flower buds of Magnolia biondii Pamp, FM) is a known herbal traditional medicine used for the symptomatic relief of nasal congestion and rhinorrhea caused by rhinitis and sinusitis. Magnolol, a neolignan from the magnolia family, is a secondary metabolite known to have anti-allergic and anti-inflammatory effects. However, the underlying mechanisms and therapeutic effect of magnolol in the treatment of allergic rhinitis (AR) remain elusive. Aims of the study: Anoctamin 1 (ANO1), a calcium-activated anion channel, mediates mucus and electrolyte secretion in nasal airway epithelial cells, whereas calcium release-activated calcium channel protein 1 (ORAI1) participates in the activation of T-lymphocytes and mast cells. The aim of our study is to understand the mechanisms of action of magnolol against AR, i.e., whether it acts through the modulation of ANO1 and ORAI1 channels that are expressed in nasal epithelial cells and T-lymphocytes, respectively. Materials and methods: Whole-cell patch clamp was used to record the activity of ORAI1 and ANO1 ion channels in ORAI1 or ANO1 overexpressed HEK293T cells, while the Ussing chamber apparatus was used to measure electrolyte transport via the epithelium, in Calu-3 cells cultured in an air-liquid interface. Additionally, calcium imaging of Jurkat T-lymphocytes was used to assess changes in the intracellular calcium concentration. Magnolol toxicity was assessed using the CCK-8 assay, and its effect on T-lymphocyte proliferation was measured by labeling human primary T-lymphocytes with carboxyfluorescein succinimidyl ester. Finally, OVA-induced Balb/c mice were employed to evaluate the effect of magnolol on nasal symptoms, as well as cytokine and eosinophil infiltration in AR. Results: Magnolol inhibits ORAI1 and ANO1 channels in a concentration-dependent manner. Magnolol (30 μM) inhibits anti-CD3 induced cellular proliferation and production of IL-2 via ORAI1 channels in T-lymphocytes. Further, ATP-induced electrolyte transport mediated by ANO1 channels is significantly inhibited by magnolol in IL-4 sensitized Calu-3 cells. Notably, 300 μM magnolol significantly attenuates cytokine and eosinophil infiltration, thus alleviating AR symptoms in mice OVA-induced AR. Conclusion: Magnolol may be a promising therapeutic agent for the treatment and prevention of AR.",

keywords = "Allergic rhinitis, Anoctamin 1, Calcium release-activated calcium channel protein 1, Calcium-activated chloride channel, magnolol",

author = "Phan, {Hong Thi Lam} and Nam, {Yu Ran} and Kim, {Hyun Jong} and Woo, {Joo Han} and Wan NamKung and Nam, {Joo Hyun} and Kim, {Woo Kyung}",

note = "Publisher Copyright: {\textcopyright} 2022 Elsevier B.V.",

year = "2022",

month = may,

day = "10",

doi = "10.1016/j.jep.2022.115061",

language = "English",

volume = "289",

journal = "Journal of Ethnopharmacology",

issn = "0378-8741",

publisher = "Elsevier Ireland Ltd",

}

Phan, HTL, Nam, YR, Kim, HJ, Woo, JH, NamKung, W, Nam, JH 2022, 'In-vitro and in-vivo anti-allergic effects of magnolol on allergic rhinitis via inhibition of ORAI1 and ANO1 channels', Journal of Ethnopharmacology, vol. 289, 115061. https://doi.org/10.1016/j.jep.2022.115061

In-vitro and in-vivo anti-allergic effects of magnolol on allergic rhinitis via inhibition of ORAI1 and ANO1 channels. / Phan, Hong Thi Lam; Nam, Yu Ran; Kim, Hyun Jong et al.
In: Journal of Ethnopharmacology, Vol. 289, 115061, 10.05.2022.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - In-vitro and in-vivo anti-allergic effects of magnolol on allergic rhinitis via inhibition of ORAI1 and ANO1 channels

AU - Phan, Hong Thi Lam

AU - Nam, Yu Ran

AU - Kim, Hyun Jong

AU - Woo, Joo Han

AU - NamKung, Wan

AU - Nam, Joo Hyun

AU - Kim, Woo Kyung

N1 - Publisher Copyright:© 2022 Elsevier B.V.

PY - 2022/5/10

Y1 - 2022/5/10

N2 - Ethnopharmacological relevance: Flos Magnoliae (the dried flower buds of Magnolia biondii Pamp, FM) is a known herbal traditional medicine used for the symptomatic relief of nasal congestion and rhinorrhea caused by rhinitis and sinusitis. Magnolol, a neolignan from the magnolia family, is a secondary metabolite known to have anti-allergic and anti-inflammatory effects. However, the underlying mechanisms and therapeutic effect of magnolol in the treatment of allergic rhinitis (AR) remain elusive. Aims of the study: Anoctamin 1 (ANO1), a calcium-activated anion channel, mediates mucus and electrolyte secretion in nasal airway epithelial cells, whereas calcium release-activated calcium channel protein 1 (ORAI1) participates in the activation of T-lymphocytes and mast cells. The aim of our study is to understand the mechanisms of action of magnolol against AR, i.e., whether it acts through the modulation of ANO1 and ORAI1 channels that are expressed in nasal epithelial cells and T-lymphocytes, respectively. Materials and methods: Whole-cell patch clamp was used to record the activity of ORAI1 and ANO1 ion channels in ORAI1 or ANO1 overexpressed HEK293T cells, while the Ussing chamber apparatus was used to measure electrolyte transport via the epithelium, in Calu-3 cells cultured in an air-liquid interface. Additionally, calcium imaging of Jurkat T-lymphocytes was used to assess changes in the intracellular calcium concentration. Magnolol toxicity was assessed using the CCK-8 assay, and its effect on T-lymphocyte proliferation was measured by labeling human primary T-lymphocytes with carboxyfluorescein succinimidyl ester. Finally, OVA-induced Balb/c mice were employed to evaluate the effect of magnolol on nasal symptoms, as well as cytokine and eosinophil infiltration in AR. Results: Magnolol inhibits ORAI1 and ANO1 channels in a concentration-dependent manner. Magnolol (30 μM) inhibits anti-CD3 induced cellular proliferation and production of IL-2 via ORAI1 channels in T-lymphocytes. Further, ATP-induced electrolyte transport mediated by ANO1 channels is significantly inhibited by magnolol in IL-4 sensitized Calu-3 cells. Notably, 300 μM magnolol significantly attenuates cytokine and eosinophil infiltration, thus alleviating AR symptoms in mice OVA-induced AR. Conclusion: Magnolol may be a promising therapeutic agent for the treatment and prevention of AR.

AB - Ethnopharmacological relevance: Flos Magnoliae (the dried flower buds of Magnolia biondii Pamp, FM) is a known herbal traditional medicine used for the symptomatic relief of nasal congestion and rhinorrhea caused by rhinitis and sinusitis. Magnolol, a neolignan from the magnolia family, is a secondary metabolite known to have anti-allergic and anti-inflammatory effects. However, the underlying mechanisms and therapeutic effect of magnolol in the treatment of allergic rhinitis (AR) remain elusive. Aims of the study: Anoctamin 1 (ANO1), a calcium-activated anion channel, mediates mucus and electrolyte secretion in nasal airway epithelial cells, whereas calcium release-activated calcium channel protein 1 (ORAI1) participates in the activation of T-lymphocytes and mast cells. The aim of our study is to understand the mechanisms of action of magnolol against AR, i.e., whether it acts through the modulation of ANO1 and ORAI1 channels that are expressed in nasal epithelial cells and T-lymphocytes, respectively. Materials and methods: Whole-cell patch clamp was used to record the activity of ORAI1 and ANO1 ion channels in ORAI1 or ANO1 overexpressed HEK293T cells, while the Ussing chamber apparatus was used to measure electrolyte transport via the epithelium, in Calu-3 cells cultured in an air-liquid interface. Additionally, calcium imaging of Jurkat T-lymphocytes was used to assess changes in the intracellular calcium concentration. Magnolol toxicity was assessed using the CCK-8 assay, and its effect on T-lymphocyte proliferation was measured by labeling human primary T-lymphocytes with carboxyfluorescein succinimidyl ester. Finally, OVA-induced Balb/c mice were employed to evaluate the effect of magnolol on nasal symptoms, as well as cytokine and eosinophil infiltration in AR. Results: Magnolol inhibits ORAI1 and ANO1 channels in a concentration-dependent manner. Magnolol (30 μM) inhibits anti-CD3 induced cellular proliferation and production of IL-2 via ORAI1 channels in T-lymphocytes. Further, ATP-induced electrolyte transport mediated by ANO1 channels is significantly inhibited by magnolol in IL-4 sensitized Calu-3 cells. Notably, 300 μM magnolol significantly attenuates cytokine and eosinophil infiltration, thus alleviating AR symptoms in mice OVA-induced AR. Conclusion: Magnolol may be a promising therapeutic agent for the treatment and prevention of AR.

KW - Allergic rhinitis

KW - Anoctamin 1

KW - Calcium release-activated calcium channel protein 1

KW - Calcium-activated chloride channel

KW - magnolol

UR - http://www.scopus.com/inward/record.url?scp=85124304095&partnerID=8YFLogxK

U2 - 10.1016/j.jep.2022.115061

DO - 10.1016/j.jep.2022.115061

M3 - Article

C2 - 35114342

AN - SCOPUS:85124304095

SN - 0378-8741

VL - 289

JO - Journal of Ethnopharmacology

JF - Journal of Ethnopharmacology

M1 - 115061

ER -

Phan HTL, Nam YR, Kim HJ, Woo JH, NamKung W, Nam JH et al. In-vitro and in-vivo anti-allergic effects of magnolol on allergic rhinitis via inhibition of ORAI1 and ANO1 channels. Journal of Ethnopharmacology. 2022 May 10;289:115061. doi: 10.1016/j.jep.2022.115061