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.