Nutraceutical Aid for Allergies – Strategies for Down-Regulating Mast Cell Degranulation

Abstract

Interactions of antigens with the mast cell FcεRI-IgE receptor complex induce degranulation and boost synthesis of pro-inflammatory lipid mediators and cytokines. Activation of spleen tyrosine kinase (Syk) functions as a central hub in this signaling. The tyrosine phosphatase SHP-1 opposes Syk activity; stimulation of NADPH oxidase by FcεRI activation results in the production of oxidants that reversibly inhibit SHP-1, up-regulating the signal from Syk. Activated AMPK can suppress Syk activation by the FcεRI receptor, possibly reflecting its ability to phosphorylate the FcεRI beta subunit. Cyclic GMP, via protein kinase G II, enhances the activity of SHP-1 by phosphorylating its C-terminal region; this may explain its inhibitory impact on mast cell activation. Hydrogen sulfide (H 2 S) likewise opposes mast cell activation; H 2 S can boost AMPK activity, up-regulate cGMP production, and trigger Nrf2-mediated induction of Phase 2 enzymes -including heme oxygenase-1, whose generation of bilirubin suppresses NADPH oxidase activity. Phycocyanobilin (PCB), a chemical relative of bilirubin, shares its inhibitory impact on NADPH oxidase, rationalizing reported anti-allergic effects of PCB-rich spirulina ingestion. Phase 2 inducer nutraceuticals can likewise oppose the up-regulatory impact of NADPH oxidase on FcεRI signaling. AMPK can be activated with the nutraceutical berberine. Highdose biotin can boost cGMP levels in mast cells via direct stimulation of soluble guanylate cyclase. Endogenous generation of H 2 S in mast cells can be promoted by administering N-acetylcysteine and likely by taurine, which increases the expression of H 2 S-producing enzymes in the vascular system. Mast cell stabilization by benifuuki green tea catechins may reflect the decreased surface expression of FcεRI.

CKBA suppresses mast cell activation via ERK signaling pathway in murine atopic dermatitis

“…FcεRI comprises four polypeptide chains and can be banded with both extracellular domains of the IgE α chain [42]. The downstream activation of phosphatidylinositol-3kinase (PI3K), MAP kinases, phospholipase C-γ, and NADPH oxidase can promote mast cell activation by phosphorylating the β and γ chains of FcεRI [43,44]. A recent study found that targeting MAPK signaling pathway could restrain mast cell activation and limit AD [45].…”