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Review - Nutraceuticals Can Target Asthmatic Bronchoconstriction: NADPH Oxidase-Dependent Oxidative Stress, RhoA and
Mark F McCarty1, James J DiNicolantonio2, Aaron Lerner3
1Catalytic Longevity Foundation, San Diego, CA, USA.
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.
Insights
NADPH oxidase activation drives asthma. Bilirubin and its homolog phycocyanobilin (PhyCB) from spirulina inhibit this enzyme. PhyCB and other nutraceuticals show promise for asthma management.
Area of Science:
- Biochemistry
- Immunology
- Pharmacology
Background:
- NADPH oxidase (NOX) activation is central to asthma pathogenesis, affecting airway smooth muscle, eosinophil influx, and mast cell activation.
- Free bilirubin inhibits NOX activity, suggesting a protective role against asthma.
- Phycocyanobilin (PhyCB), a spirulina component, mimics bilirubin's NOX inhibitory effects, with demonstrated anti-inflammatory properties in animal models.
Purpose of the Study:
- To explore the potential of nutraceuticals, including spirulina and its component PhyCB, as therapeutic agents for asthma.
- To investigate the role of oxidative stress and related pathways in asthma pathogenesis.
- To identify compounds that can modulate NOX activity, antioxidant pathways, and smooth muscle function in asthma.
Main Methods:
- Review of existing literature on NADPH oxidase, bilirubin, phycocyanobilin, and asthma pathophysiology.
- Analysis of proposed mechanisms for nutraceutical intervention in asthma, including NOX inhibition, antioxidant enzyme induction, and modulation of signaling pathways.
- Exploration of the roles of nitric oxide (NO), hydrogen sulfide (H2S), and other signaling molecules in asthma.
Main Results:
- PhyCB from spirulina can inhibit NOX activity, similar to bilirubin, and exhibits anti-inflammatory effects.
- Supplementation with N-acetylcysteine, lipoic acid, selenium, and zinc may reduce oxidative stress in asthma.
- Citrulline, folate, biotin, N-acetylcysteine, taurine, glycine, and magnesium are identified as potential agents to modulate NO synthesis, H2S synthesis, smooth muscle function, and bronchoconstriction.
Conclusions:
- Spirulina or PhyCB-enriched extracts warrant clinical evaluation for asthma treatment.
- Nutraceutical regimens incorporating agents like N-acetylcysteine, antioxidants, and modulators of NO and H2S pathways may serve as adjunctive therapies for asthma.
- Targeting NOX and oxidative stress pathways with specific nutraceuticals offers a promising strategy for managing asthma.
