Anti-Allergic Effect of Dietary Polyphenols Curcumin and Epigallocatechin Gallate via Anti-Degranulation in IgE/Antigen-Stimulated Mast Cell Model: A Lipidomics Perspective

Abstract

Polyphenol-rich foods exhibit anti-allergic/-inflammatory properties. As major effector cells of allergies, mast cells undergo degranulation after activation and then initiate inflammatory responses. Key immune phenomena could be regulated by the production and metabolism of lipid mediators by mast cells. Here, we analyzed the antiallergic activities of two representative dietary polyphenols, curcumin and epigallocatechin gallate (EGCG), and traced their effects on cellular lipidome rewiring in the progression of degranulation. Both curcumin and EGCG significantly inhibited degranulation as they suppressed the release of β-hexosaminidase, interleukin-4, and tumor necrosis factor-α from the IgE/antigen-stimulated mast cell model. A comprehensive lipidomics study involving 957 identified lipid species revealed that although the lipidome remodeling patterns (lipid response and composition) of curcumin intervention were considerably similar to those of EGCG, lipid metabolism was more potently disturbed by curcumin. Seventy-eight percent of significant differential lipids upon IgE/antigen stimulation could be regulated by curcumin/EGCG. LPC-O 22:0 was defined as a potential biomarker for its sensitivity to IgE/antigen stimulation and curcumin/EGCG intervention. The key changes in diacylglycerols, fatty acids, and bismonoacylglycerophosphates provided clues that cell signaling disturbances could be associated with curcumin/EGCG intervention. Our work supplies a novel perspective for understanding curcumin/EGCG involvement in antianaphylaxis and helps guide future attempts to use dietary polyphenols.

Dietary Polyphenols, Plant Metabolites, and Allergic Disorders: A Comprehensive Review

“…Indeed, curcumin, resveratrol, rosmarinic acid, and these phenolic compounds all showed strong inhibitory effects on histamine and β-hexosaminidase release. These enzymes are used to measure the extent of mast cell degranulation [ 212 , 213 , 214 ]. Furthermore, polyphenols have been found to effectively inhibit the signaling cascades of both FcεRI-mediated protein kinases (Syk, Lyn, PLCγ, PKC) and the MAPK and the NF-κB signaling pathways, which play a crucial role in allergic reactions.…”

Dietary Polyphenols—Natural Bioactive Compounds with Potential for Preventing and Treating Some Allergic Conditions

“…Moreover, the ability to stabilize mast cell membranes and thus suppress their degranulation has been demonstrated for certain polyphenols, including quercetin, phlorotannins, luteolin, and myricetin, which have been found to downregulate the expression of calcium channel proteins and inhibit calcium influx and intracellular calcium elevation necessary for the degranulation in mast cells [107,138,[146][147][148]. Indeed, these phenolic compounds, along with curcumin, EGCG, rosmarinic acid, and resveratrol, exhibited pronounced inhibitory effects on the release of histamine and β-hexosaminidase, which are used as markers to evaluate the level of mast cell degranulation [104,107,141,144,[146][147][148][149][150][151]. In addition, polyphenols have been reported as potent suppressor of both FcεRI mediated protein kinases (Syk, Lyn, PLCγ, PKC) signaling cascade and the MAPK and the NF-κB signaling pathway that are critical for the allergic reaction, resulting in attenuating secretion of pro-inflammatory cytokines (IL-4, TNF-α) in and synthesis of lipid mediators (prostaglandin D2, leukotrienes) [144,146,149,150,[152][153][154].…”

“…Indeed, these phenolic compounds, along with curcumin, EGCG, rosmarinic acid, and resveratrol, exhibited pronounced inhibitory effects on the release of histamine and β-hexosaminidase, which are used as markers to evaluate the level of mast cell degranulation [104,107,141,144,[146][147][148][149][150][151]. In addition, polyphenols have been reported as potent suppressor of both FcεRI mediated protein kinases (Syk, Lyn, PLCγ, PKC) signaling cascade and the MAPK and the NF-κB signaling pathway that are critical for the allergic reaction, resulting in attenuating secretion of pro-inflammatory cytokines (IL-4, TNF-α) in and synthesis of lipid mediators (prostaglandin D2, leukotrienes) [144,146,149,150,[152][153][154]. Interestingly, Yong et al confirmed the anti-allergic potential of stingless bee honey (Kelulut honey) in terms of mast cell activation and degranulation; however, the inhibitory effect was strictly dependent on the botanical source of honey as it was only indicated in the case of rich in polyphenols honey obtained from bamboo and rubber trees, while honey poorer in polyphenols sourced from noni and mango did not show such anti-allergic action [155].…”

“…Curcumin is another non-flavonoid polyphenol for which a favorable therapeutic effect on allergic rhinitis has been reported in studies on animal models, pointing out that treatment with curcumin resulted in suppression of allergen-induced allergic rhinitis symptoms and histopathological features such as goblet cell metaplasia, infiltration of the inflammatory cell and vascular proliferation in nasal tissue [150,172,262]. Wu et al conducted a randomized, double-blind study in allergic rhinitis patients, providing evidence that orally administered curcumin is able to modulate immune response, remarkably mitigate the nasal symptoms (sneezing, itching, rhinorrhea), and increase the nasal airflow, thus relieving the obstruction [263].…”

Tea for histamine anti-allergy: component analysis of tea extracts and potential mechanism for treating histamine anti-allergy

“…Skin hypersensitivity is the most common type of hypersensitivity mediated by lgE ( Feinberg, 2018 ), where mast cells act as the main response cells ( Khan and Kemp, 2011 ; Hagemann et al, 2019 ). The mechanism is that antigens enter the body and bind to lgE attached to mast cells and basophils ( Gilfillan and Tkaczyk, 2006 ; Wernersson and Pejler, 2014 ), inducing cells to be activated and release histamine, 5-hydroxytryptamine and other bioactive substances ( Nitschke et al, 1996 ; Zeng et al, 2023 ). Histamine is the main chemical mediator of immune and inflammatory responses ( Li H. et al, 2022 ; Ke et al, 2023 ).…”