https://orcid.org/0000-0002-6779-4090
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Abstract
Activation of various isoforms of NADPH oxidase contributes to the pathogenesis of asthma at multiple levels: promoting hypercontractility, hypertrophy, and proliferation of airway smooth muscle; enabling lung influx of eosinophils via VCAM-1; and mediating allergen-induced mast cell activation. Free bilirubin, which functions physiologically within cells as a feedback inhibitor of NADPH oxidase complexes, has been shown to have a favorable impact on each of these phases of asthma pathogenesis. The spirulina chromophore phycocyanobilin (PhyCB), a homolog of bilirubin’s precursor biliverdin, can mimic the inhibitory impact of biliverdin/bilirubin on NADPH oxidase activity, and spirulina’s versatile and profound anti-inflammatory activity in rodent studies suggests that PhyCB may have potential as a clinical inhibitor of NADPH oxidase. Hence, spirulina or PhyCB-enriched spirulina extracts merit clinical evaluation in asthma. Promoting biosynthesis of glutathione and increasing the expression and activity of various antioxidant enzymes – as by supplementing with N-acetylcysteine, Phase 2 inducers (eg, lipoic acid), selenium, and zinc – may also blunt the contribution of oxidative stress to asthma pathogenesis. Nitric oxide (NO) and hydrogen sulfide (H2S) work in various ways to oppose pathogenic mechanisms in asthma; supplemental citrulline and high-dose folate may aid NO synthesis, high-dose biotin may mimic and possibly potentiate NO’s activating impact on soluble guanylate cyclase, and NAC and taurine may boost H2S synthesis. The amino acid glycine has a hyperpolarizing effect on airway smooth muscle that is bronchodilatory. Insuring optimal intracellular levels of magnesium may modestly blunt the stimulatory impact of intracellular free calcium on bronchoconstriction. Nutraceutical regimens or functional foods incorporating at least several of these agents may have utility as nutraceutical adjuvants to standard clinical management of asthma.
Abbreviations
PhyCB, phycocyanobilin; NO, nitric oxide; H2S, hydrogen sulfide; ROCK, Rho-activated kinase; MLCP, myosin light chain phosphatase; C-PKC, protein kinase; C-PLC, phospholipase; sGC, soluble guanylate cyclase; cGMP, cyclic GMP; G-PKG, protein kinase; ASM, airway smooth muscle; BALF, bronchoalveolar fluid; NAC, N-acetylcysteine; LA, lipoic acid; DDAH, dimethylarginine dimethylaminohydrolase; ADMA, asymmetric dimethylarginine; iNOS, inducible NO synthase; MT, Metallothionein; PDE5, phosphodiesterase 5; CBS, cystathionine β-synthase; CSE, cystathionine γ-lyase ; FEV1, forced expiratory volume in one second; Mg, magnesium.
Acknowledgments
An essay entitled “Spirulina and its Chromophore Phycocyanobilin have Potential for Alleviation of Asthma“, written by Mark F. McCarty, appeared previously on the author's personal website http://catalyticlongevity.org. A small portion of the language in the present paper was derived from that previous essay.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
Co-author MFM is co-inventor and co-owner of a US patent (US 8,709,434) on nutraceutical uses of phycocyanobilin oligopeptides derived from spirulina and reports a patent US 8,709,434 with royalities paid to JDS Therapeutics, Inc. JJD is an employee for Advanced Ingredients for Dietary Products. The authors report no other conflicts of interest in this work.