Journal of Asthma and Allergy (Oct 2021)
Nutraceutical Aid for Allergies – Strategies for Down-Regulating Mast Cell Degranulation
Abstract
Mark F McCarty,1 Aaron Lerner,2 James J DiNicolantonio,3,4 Carina Benzvi2 1Catalytic Longevity Foundation, San Diego, CA, USA; 2Chaim Sheba Medical Center, The Zabludowicz Research Center for Autoimmune Diseases, Tel Hashomer, Israel; 3Saint Luke’s Mid America Heart Institute, Kansas City, MO, USA; 4Advanced Ingredients for Dietary Products, AIDP, City of Industry, CA, USACorrespondence: Aaron LernerChaim Sheba Medical Center, The Zabludowicz Research Center for Autoimmune Diseases, Tel Hashomer, 5262000, IsraelTel +972-525-919484Email [email protected]: 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 (H2S) likewise opposes mast cell activation; H2S 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. High-dose biotin can boost cGMP levels in mast cells via direct stimulation of soluble guanylate cyclase. Endogenous generation of H2S in mast cells can be promoted by administering N-acetylcysteine and likely by taurine, which increases the expression of H2S-producing enzymes in the vascular system. Mast cell stabilization by benifuuki green tea catechins may reflect the decreased surface expression of FcϵRI.Keywords: nutraceuticals, mast cell, degranulation, allergy, FcϵRI-IgE receptor, hydrogen sulfide, phycocyanobilin, berberine, biotin, lipoic acid
