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.

Keywords: asthma, bronchoconstriction, calcium, NADPH oxidase, RhoA, oxidative stress

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评论 – 营养食品可以针对哮喘性支气管收缩：NADPH 氧化酶依赖性氧化应激、RhoA 和钙动力学

摘要：NADPH氧化酶的各种同工型的激活在多个层面促成哮喘的发病机制：促进气道平滑肌过度收缩、肥大和增殖；通过 VCAM-1 使嗜酸性粒细胞流入肺；并介导过敏原诱导的肥大细胞活化。游离胆红素在细胞内作为 NADPH 氧化酶复合物的反馈抑制剂在生理上起作用，已被证明对哮喘发病机制的每个阶段都有有利的影响。螺旋藻发色团藻蓝胆素 (PhyCB) 是胆红素前体胆绿素的同系物，可以模拟胆绿素/胆红素对 NADPH 氧化酶活性的抑制作用，并且螺旋藻在啮齿类动物研究中的多功能和深远的抗炎活性表明 PhyCB 可能具有作为临床应用的潜力。 NADPH氧化酶抑制剂。因此，螺旋藻或富含 PhyCB 的螺旋藻提取物在哮喘中值得临床评估。促进谷胱甘肽的生物合成并增加各种抗氧化酶的表达和活性——如通过补充 N-乙酰半胱氨酸、第 2 阶段诱导剂（如硫辛酸）、硒和锌——也可能减弱氧化应激对哮喘发病机制的贡献。一氧化氮 (NO) 和硫化氢 (H₂ S) 以多种方式对抗哮喘的致病机制；补充瓜氨酸和高剂量叶酸可能有助于 NO 合成，高剂量生物素可能模拟并可能增强 NO 对可溶性鸟苷酸环化酶的激活影响，NAC 和牛磺酸可能促进 H ₂ S 合成。氨基酸甘氨酸对支气管扩张的气道平滑肌具有超极化作用。确保最佳的细胞内镁水平可以适度减弱细胞内游离钙对支气管收缩的刺激作用。包含至少几种这些药剂的营养保健品方案或功能性食品可用作哮喘标准临床管理的营养保健品佐剂。

关键词： 哮喘、支气管收缩、钙、NADPH 氧化酶、RhoA、氧化应激