Turowski Jason B, Pietrofesa Ralph A, Lawson John A, Christofidou-Solomidou Melpo, Hadjiliadis Denis
Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pennsylvania, Hospital of the University of Pennsylvania, 835W Gates Building, 3600, Spruce Street, Philadelphia, PA, 19104, USA.
Department of Pharmacology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104, USA.
BMC Complement Altern Med. 2015 May 13;15:148. doi: 10.1186/s12906-015-0651-2.
Cystic fibrosis (CF) leads to advanced lung disease despite aggressive care. Persistent inflammation and oxidative stress contribute to exacerbations and disease progression. Flaxseed (FS), a dietary botanical supplement with high fiber, lignan phenolics, and omega-3 fatty acids has anti-inflammatory and antioxidant properties in murine models of acute and chronic lung injury. This pilot study was designed to determine whether CF patients could tolerate FS, evaluate circulating FS metabolites, and study biomarkers of lung damage, as a prelude to studying clinical outcomes.
10 CF patients and 5 healthy volunteers consumed 40 g of FS daily for 4 weeks with safety and tolerability being assessed. Urine was evaluated for systemic oxidative stress and plasma for FS metabolites (enterolignans) and cytokine levels. Buccal swabs were analyzed for gene expression of Nrf2-regulated antioxidant enzymes including Heme Oxygenase-1 (HO-1) and NAD(P)H Quinone Oxidoreductase 1 (NQO1).
All subjects completed the study without serious adverse events. Plasma levels of enterolignans were detectable in both healthy controls and CF volunteers. CF patients were stratified based on plasma enterolignan levels after 2 weeks of FS administration into high- (174 to 535 nM ED and 232 to 1841 nM EL) and low- (0 to 32 nM ED and 0 to 40 nM EL) plasma lignan cohorts. The low enterolignan level cohort experienced a statistically significant drop in urinary inflammatory IsoP and plasma TNFα levels, while demonstrating higher average NQO1 mRNA levels in buccal epithelium compared to high-lignan patients.
This pilot study demonstrated that FS is tolerated by CF patients. FS metabolites could be detected in the plasma. Future studies will assess appropriate dosing and target populations for FS, while exploring clinical outcomes.
ClinicalTrials.gov identifier: NCT02014181 .
尽管采取了积极的治疗措施，囊性纤维化（CF）仍会导致晚期肺部疾病。持续的炎症和氧化应激会促使病情加重和疾病进展。亚麻籽（FS）是一种富含高纤维、木脂酚类和ω-3脂肪酸的膳食植物补充剂，在急性和慢性肺损伤的小鼠模型中具有抗炎和抗氧化特性。这项初步研究旨在确定CF患者是否能够耐受FS，评估循环中的FS代谢产物，并研究肺损伤的生物标志物，作为研究临床结果的前奏。
10名CF患者和5名健康志愿者每天食用40克FS，持续4周，并评估安全性和耐受性。检测尿液中的全身氧化应激，检测血浆中的FS代谢产物（肠木脂素）和细胞因子水平。分析颊拭子中Nrf2调节的抗氧化酶的基因表达，包括血红素加氧酶-1（HO-1）和NAD（P）H醌氧化还原酶1（NQO1）。
所有受试者均完成研究，无严重不良事件。健康对照组和CF志愿者的血浆中均可检测到肠木脂素水平。在服用FS 2周后，根据血浆肠木脂素水平将CF患者分为高血浆木脂素组（174至535 nM ED和232至1841 nM EL）和低血浆木脂素组（0至32 nM ED和0至40 nM EL）。低肠木脂素水平组的尿炎性异前列腺素和血浆TNFα水平有统计学意义的下降，同时与高木脂素患者相比，颊上皮中的平均NQO1 mRNA水平更高。
这项初步研究表明CF患者能够耐受FS。血浆中可检测到FS代谢产物。未来的研究将评估FS的合适剂量和目标人群，同时探索临床结果。
ClinicalTrials.gov标识符：NCT02014181 。
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