Anti-Allergic Potential of Cinnamaldehyde via the Inhibitory Effect of Histidine Decarboxylase (HDC) Producing Klebsiella pneumonia.

Promise Madu Emeka,Krishnaraj Thirugnanasambantham,Hairul Islam M Ibrahim,Lorina I Badger-Emeka

doi:10.3390/molecules25235580

Promise Madu Emeka, Krishnaraj Thirugnanasambantham + Show 2 more

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https://doi.org/10.3390/molecules25235580

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Abstract

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 Klebsiella pneumoniae 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 K. pneumonia 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.

Highlights

Allergic disorders are on the rise globally, creating global health concerns [1,2]
The primary, secondary, and 3D structure properties; amino acid composition; Ramachandran plot analysis; and G-factor parameters are presented in Figure 1a–e and Tables S1–S4 (Supplementary Data)
We have demonstrated that CA potentially inhibits both bacterial and RBL-2H3 cells’ histidine decarboxylase (HDC)

Summary

Introduction

Allergic disorders are on the rise globally, creating global health concerns [1,2]. Allergy is considered an immunological disorder which develops in response to exposure either to an allergen that could be airborne or from drugs, food, or animals. The resulting immunological disorders can subsequently present in different forms, such as asthma, urticarial, allergic rhinitis, food allergies, and anaphylaxis, which is life threatening [2]. The high prevalence of these allergic disorders cuts across the developed and underdeveloped world, with a resulting deterioration in quality of life, as it is a substantial economic burden. An estimated 25 billion dollars is reportedly used annually in the United States of America (USA). For the treatment of food allergies [3].

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