Anti-Allergic Potential of Cinnamaldehyde via the Inhibitory Effect of Histidine Decarboxylase (HDC) Producing <i>Klebsiella pneumonia</i>
Allergy is an immunological disorder that develops in response to exposure to an allergen, and histamines mediate these effects via histidine decarboxylase (HDC) activity at the intracellular level. In the present study, we developed a 3D model of <i>Klebsiella pneumoniae</i> histidine d...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-11-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/25/23/5580 |
| _version_ | 1797546483840450560 |
|---|---|
| author | Lorina I. Badger-Emeka Promise Madu Emeka Krishnaraj Thirugnanasambantham Hairul Islam M. Ibrahim |
| author_facet | Lorina I. Badger-Emeka Promise Madu Emeka Krishnaraj Thirugnanasambantham Hairul Islam M. Ibrahim |
| author_sort | Lorina I. Badger-Emeka |
| collection | DOAJ |
| description | Allergy is an immunological disorder that develops in response to exposure to an allergen, and histamines mediate these effects via histidine decarboxylase (HDC) activity at the intracellular level. In the present study, we developed a 3D model of <i>Klebsiella pneumoniae</i> histidine decarboxylase (HDC) and analyzed the HDC inhibitory potential of cinnamaldehyde (CA) and subsequent anti-allergic potential using a bacterial and mammalian mast cell model. A computational and in vitro study using <i>K. pneumonia</i> revealed that CA binds to HDC nearby the pyridoxal-5′-phosphate (PLP) binding site and inhibited histamine synthesis in a bacterial model. Further study using a mammalian mast cell model also showed that CA decreased the levels of histamine in the stimulated RBL-2H3 cell line and attenuated the release of β-hexoseaminidase and cell degranulation. In addition, CA treatment also significantly suppressed the levels of pro-inflammatory cytokines TNF-α and IL-6 and the nitric oxide (NO) level in the stimulated mast cells. A gene expression and Western blotting study revealed that CA significantly downregulated the expressions of MAPKp38/ERK and its downstream pro-allergic mediators that are involved in the signaling pathway in mast cell cytokine synthesis. This study further confirms that CA has the potential to attenuate mast cell activation by inhibiting HDC and modifying the process of allergic disorders. |
| first_indexed | 2024-03-10T14:30:34Z |
| format | Article |
| id | doaj.art-b81522a06f2b4a928808cc2fca066031 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T14:30:34Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b81522a06f2b4a928808cc2fca0660312023-11-20T22:39:23ZengMDPI AGMolecules1420-30492020-11-012523558010.3390/molecules25235580Anti-Allergic Potential of Cinnamaldehyde via the Inhibitory Effect of Histidine Decarboxylase (HDC) Producing <i>Klebsiella pneumonia</i>Lorina I. Badger-Emeka0Promise Madu Emeka1Krishnaraj Thirugnanasambantham2Hairul Islam M. Ibrahim3Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi ArabiaDepartment of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi ArabiaPondicherry Centre for Biological Science and Educational Trust, Kottakuppam 605104, Tamilnadu, IndiaDepartment of Biological Sciences, College of Science, King Faisal University, Al-Ahsa 31982, Saudi ArabiaAllergy is an immunological disorder that develops in response to exposure to an allergen, and histamines mediate these effects via histidine decarboxylase (HDC) activity at the intracellular level. In the present study, we developed a 3D model of <i>Klebsiella pneumoniae</i> histidine decarboxylase (HDC) and analyzed the HDC inhibitory potential of cinnamaldehyde (CA) and subsequent anti-allergic potential using a bacterial and mammalian mast cell model. A computational and in vitro study using <i>K. pneumonia</i> revealed that CA binds to HDC nearby the pyridoxal-5′-phosphate (PLP) binding site and inhibited histamine synthesis in a bacterial model. Further study using a mammalian mast cell model also showed that CA decreased the levels of histamine in the stimulated RBL-2H3 cell line and attenuated the release of β-hexoseaminidase and cell degranulation. In addition, CA treatment also significantly suppressed the levels of pro-inflammatory cytokines TNF-α and IL-6 and the nitric oxide (NO) level in the stimulated mast cells. A gene expression and Western blotting study revealed that CA significantly downregulated the expressions of MAPKp38/ERK and its downstream pro-allergic mediators that are involved in the signaling pathway in mast cell cytokine synthesis. This study further confirms that CA has the potential to attenuate mast cell activation by inhibiting HDC and modifying the process of allergic disorders.https://www.mdpi.com/1420-3049/25/23/5580allergyhistidine decarboxylasecinnamaldehydemast cell<i>Klebsiella pneumoniae</i>cytokines |
| spellingShingle | Lorina I. Badger-Emeka Promise Madu Emeka Krishnaraj Thirugnanasambantham Hairul Islam M. Ibrahim Anti-Allergic Potential of Cinnamaldehyde via the Inhibitory Effect of Histidine Decarboxylase (HDC) Producing <i>Klebsiella pneumonia</i> Molecules allergy histidine decarboxylase cinnamaldehyde mast cell <i>Klebsiella pneumoniae</i> cytokines |
| title | Anti-Allergic Potential of Cinnamaldehyde via the Inhibitory Effect of Histidine Decarboxylase (HDC) Producing <i>Klebsiella pneumonia</i> |
| title_full | Anti-Allergic Potential of Cinnamaldehyde via the Inhibitory Effect of Histidine Decarboxylase (HDC) Producing <i>Klebsiella pneumonia</i> |
| title_fullStr | Anti-Allergic Potential of Cinnamaldehyde via the Inhibitory Effect of Histidine Decarboxylase (HDC) Producing <i>Klebsiella pneumonia</i> |
| title_full_unstemmed | Anti-Allergic Potential of Cinnamaldehyde via the Inhibitory Effect of Histidine Decarboxylase (HDC) Producing <i>Klebsiella pneumonia</i> |
| title_short | Anti-Allergic Potential of Cinnamaldehyde via the Inhibitory Effect of Histidine Decarboxylase (HDC) Producing <i>Klebsiella pneumonia</i> |
| title_sort | anti allergic potential of cinnamaldehyde via the inhibitory effect of histidine decarboxylase hdc producing i klebsiella pneumonia i |
| topic | allergy histidine decarboxylase cinnamaldehyde mast cell <i>Klebsiella pneumoniae</i> cytokines |
| url | https://www.mdpi.com/1420-3049/25/23/5580 |
| work_keys_str_mv | AT lorinaibadgeremeka antiallergicpotentialofcinnamaldehydeviatheinhibitoryeffectofhistidinedecarboxylasehdcproducingiklebsiellapneumoniai AT promisemaduemeka antiallergicpotentialofcinnamaldehydeviatheinhibitoryeffectofhistidinedecarboxylasehdcproducingiklebsiellapneumoniai AT krishnarajthirugnanasambantham antiallergicpotentialofcinnamaldehydeviatheinhibitoryeffectofhistidinedecarboxylasehdcproducingiklebsiellapneumoniai AT hairulislammibrahim antiallergicpotentialofcinnamaldehydeviatheinhibitoryeffectofhistidinedecarboxylasehdcproducingiklebsiellapneumoniai |