Inhibition of TRPA1, Endoplasmic Reticulum Stress, Human Airway Epithelial Cell Damage, and Ectopic <i>MUC5AC</i> Expression by Vasaka (<i>Adhatoda vasica</i>; Malabar Nut) Tea
This study tested whether a medicinal plant, Vasaka, typically consumed as a tea to treat respiratory malaise, could protect airway epithelial cells (AECs) from wood smoke particle-induced damage and prevent pathological mucus production. Wood/biomass smoke is a pneumotoxic air pollutant. Mucus norm...
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MDPI AG
2023-06-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/16/6/890 |
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| author | Tosifa A. Memon Lili Sun Marysol Almestica-Roberts Cassandra E. Deering-Rice Philip J. Moos Christopher A. Reilly |
| author_facet | Tosifa A. Memon Lili Sun Marysol Almestica-Roberts Cassandra E. Deering-Rice Philip J. Moos Christopher A. Reilly |
| author_sort | Tosifa A. Memon |
| collection | DOAJ |
| description | This study tested whether a medicinal plant, Vasaka, typically consumed as a tea to treat respiratory malaise, could protect airway epithelial cells (AECs) from wood smoke particle-induced damage and prevent pathological mucus production. Wood/biomass smoke is a pneumotoxic air pollutant. Mucus normally protects the airways, but excessive production can obstruct airflow and cause respiratory distress. Vasaka tea pre- and co-treatment dose-dependently inhibited mucin 5AC (<i>MUC5AC</i>) mRNA induction by AECs treated with wood smoke particles. This correlated with transient receptor potential ankyrin-1 (TRPA1) inhibition, an attenuation of endoplasmic reticulum (ER) stress, and AEC damage/death. Induction of mRNA for anterior gradient 2, an ER chaperone/disulfide isomerase required for <i>MUC5AC</i> production, and TRP vanilloid-3, a gene that suppresses ER stress and wood smoke particle-induced cell death, was also attenuated. Variable inhibition of TRPA1, ER stress, and <i>MUC5AC</i> mRNA induction was observed using selected chemicals identified in Vasaka tea including vasicine, vasicinone, apigenin, vitexin, isovitexin, isoorientin, 9-oxoODE, and 9,10-EpOME. Apigenin and 9,10-EpOME were the most cytoprotective and mucosuppressive. Cytochrome P450 1A1 (CYP1A1) mRNA was also induced by Vasaka tea and wood smoke particles. Inhibition of CYP1A1 enhanced ER stress and <i>MUC5AC</i> mRNA expression, suggesting a possible role in producing protective oxylipins in stressed cells. The results provide mechanistic insights and support for the purported benefits of Vasaka tea in treating lung inflammatory conditions, raising the possibility of further development as a preventative and/or restorative therapy. |
| first_indexed | 2024-03-11T02:02:54Z |
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| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-11T02:02:54Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-25f254a5690442ce99c1e423d491d7522023-11-18T12:03:00ZengMDPI AGPharmaceuticals1424-82472023-06-0116689010.3390/ph16060890Inhibition of TRPA1, Endoplasmic Reticulum Stress, Human Airway Epithelial Cell Damage, and Ectopic <i>MUC5AC</i> Expression by Vasaka (<i>Adhatoda vasica</i>; Malabar Nut) TeaTosifa A. Memon0Lili Sun1Marysol Almestica-Roberts2Cassandra E. Deering-Rice3Philip J. Moos4Christopher A. Reilly5Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah Health, Salt Lake City, UT 84112, USADepartment of Pharmacology and Toxicology, College of Pharmacy, University of Utah Health, Salt Lake City, UT 84112, USADepartment of Pharmacology and Toxicology, College of Pharmacy, University of Utah Health, Salt Lake City, UT 84112, USADepartment of Pharmacology and Toxicology, College of Pharmacy, University of Utah Health, Salt Lake City, UT 84112, USADepartment of Pharmacology and Toxicology, College of Pharmacy, University of Utah Health, Salt Lake City, UT 84112, USADepartment of Pharmacology and Toxicology, College of Pharmacy, University of Utah Health, Salt Lake City, UT 84112, USAThis study tested whether a medicinal plant, Vasaka, typically consumed as a tea to treat respiratory malaise, could protect airway epithelial cells (AECs) from wood smoke particle-induced damage and prevent pathological mucus production. Wood/biomass smoke is a pneumotoxic air pollutant. Mucus normally protects the airways, but excessive production can obstruct airflow and cause respiratory distress. Vasaka tea pre- and co-treatment dose-dependently inhibited mucin 5AC (<i>MUC5AC</i>) mRNA induction by AECs treated with wood smoke particles. This correlated with transient receptor potential ankyrin-1 (TRPA1) inhibition, an attenuation of endoplasmic reticulum (ER) stress, and AEC damage/death. Induction of mRNA for anterior gradient 2, an ER chaperone/disulfide isomerase required for <i>MUC5AC</i> production, and TRP vanilloid-3, a gene that suppresses ER stress and wood smoke particle-induced cell death, was also attenuated. Variable inhibition of TRPA1, ER stress, and <i>MUC5AC</i> mRNA induction was observed using selected chemicals identified in Vasaka tea including vasicine, vasicinone, apigenin, vitexin, isovitexin, isoorientin, 9-oxoODE, and 9,10-EpOME. Apigenin and 9,10-EpOME were the most cytoprotective and mucosuppressive. Cytochrome P450 1A1 (CYP1A1) mRNA was also induced by Vasaka tea and wood smoke particles. Inhibition of CYP1A1 enhanced ER stress and <i>MUC5AC</i> mRNA expression, suggesting a possible role in producing protective oxylipins in stressed cells. The results provide mechanistic insights and support for the purported benefits of Vasaka tea in treating lung inflammatory conditions, raising the possibility of further development as a preventative and/or restorative therapy.https://www.mdpi.com/1424-8247/16/6/890VasakaTRPA1airway epitheliummucus hypersecretion<i>MUC5AC</i>lung injury |
| spellingShingle | Tosifa A. Memon Lili Sun Marysol Almestica-Roberts Cassandra E. Deering-Rice Philip J. Moos Christopher A. Reilly Inhibition of TRPA1, Endoplasmic Reticulum Stress, Human Airway Epithelial Cell Damage, and Ectopic <i>MUC5AC</i> Expression by Vasaka (<i>Adhatoda vasica</i>; Malabar Nut) Tea Pharmaceuticals Vasaka TRPA1 airway epithelium mucus hypersecretion <i>MUC5AC</i> lung injury |
| title | Inhibition of TRPA1, Endoplasmic Reticulum Stress, Human Airway Epithelial Cell Damage, and Ectopic <i>MUC5AC</i> Expression by Vasaka (<i>Adhatoda vasica</i>; Malabar Nut) Tea |
| title_full | Inhibition of TRPA1, Endoplasmic Reticulum Stress, Human Airway Epithelial Cell Damage, and Ectopic <i>MUC5AC</i> Expression by Vasaka (<i>Adhatoda vasica</i>; Malabar Nut) Tea |
| title_fullStr | Inhibition of TRPA1, Endoplasmic Reticulum Stress, Human Airway Epithelial Cell Damage, and Ectopic <i>MUC5AC</i> Expression by Vasaka (<i>Adhatoda vasica</i>; Malabar Nut) Tea |
| title_full_unstemmed | Inhibition of TRPA1, Endoplasmic Reticulum Stress, Human Airway Epithelial Cell Damage, and Ectopic <i>MUC5AC</i> Expression by Vasaka (<i>Adhatoda vasica</i>; Malabar Nut) Tea |
| title_short | Inhibition of TRPA1, Endoplasmic Reticulum Stress, Human Airway Epithelial Cell Damage, and Ectopic <i>MUC5AC</i> Expression by Vasaka (<i>Adhatoda vasica</i>; Malabar Nut) Tea |
| title_sort | inhibition of trpa1 endoplasmic reticulum stress human airway epithelial cell damage and ectopic i muc5ac i expression by vasaka i adhatoda vasica i malabar nut tea |
| topic | Vasaka TRPA1 airway epithelium mucus hypersecretion <i>MUC5AC</i> lung injury |
| url | https://www.mdpi.com/1424-8247/16/6/890 |
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