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

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.

Rosa davurica Inhibited Allergic Mediators by Regulating Calcium and Histamine Signaling Pathways

“…In this study, RLE was demonstrated to act on the mRNA and protein expression of HDC–the sole enzyme that functions in histamine production from histidine ( Figure 8 ). The pharmacological study reported that mRNA and protein expression of HDC was inhibited by mitogen-activated protein kinase (MEK) and c-Jun terminal kinase inhibitor, demonstrating that the MAPK pathway plays a significant role in the transduction of inhibitory signals to suppress HDC expression [ 25 ]. The results suggested that the regulatory mechanism of RLE on HDC was mediated by downregulating MAPK signaling, consequently exerting the activity of transcription factors of the HDC gene, including GATA2, MITF, SP1, and KLF4 ( Figure 9 ).…”

Effect of Cinnamon on Distribution and Number of Mast Cells in Diabetic Rat Liver

“…20 For this reason, experimental evidence has postulated that cinnamon reduced the degranulation of MCs, thereby regulating histamine synthesis. 21 It is thought that cinnamon plays an essential role in the intracellular mobilization of Ca ++ ions in mucosal MCs with its inhibitory effects on the phospholipase C signaling pathway. 18 Consistent with these studies, our findings showed that cinnamon extract reduced the increase in liver MCs number induced by STZ.…”

Cinnamaldehyde decreases the invasion and u-PA expression of osteosarcoma by down-regulating the FAK signalling pathway

“…C. cassia is also widely used in traditional Chinese medicine. Cinnamaldehyde, one of the most important bioactive ingredients in C. cassia , has beneficial effects, such as antibacterial, 13 anti-allergic, 14 anti-inflammatory 15 and anticancer effects. 16 Our previous study indicated that ethanoic C. cassia extracts suppresses cell invasion by repressing matrix metalloproteinase-2 and u-PA and reverses TGF-β1-induced EMT by up-regulating E-cadherin in human lung adenocarcinoma cells.…”