Abstract

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Emphysema and chronic bronchitis are the two major phenotypes of COPD, which have many symptoms, such as dyspnea, chronic cough, and mucus overproduction. Emphysema is characterized by the destruction of the alveolar wall, while chronic bronchitis is characterized by limitations in expiratory airflow. Cigarette smoking is the most significant risk factor for the pathogenesis of COPD in the developed world. Chronic inflammation contributes to the onset and progression of the disease and furthers the risk of comorbidities. Current treatment options and prevention strategies for COPD are very limited. Tocotrienols are a group of vitamin E molecules with antioxidant and anti-inflammatory properties. Individual tocotrienols (α, γ, and δ) have shown their ability to attenuate inflammation specifically via suppressing nuclear factor-κB-mediated cytokine production. The δ- and γ-forms of tocotrienols have been indicated as the most effective in the prevention of macrophage infiltration, production of reactive oxygen species, and cytokine secretion. This review briefly discusses the pathogenesis of COPD and the role of inflammation therein. Furthermore, we summarize the in vitro and in vivo evidence for the anti-inflammatory activity of tocotrienols and their potential application to COPD management. Coupled with the bioavailability and safety profile of tocotrienols, the ability of these compounds to modulate COPD progression by targeting the inflammation pathways renders them potential candidates for novel therapeutic approaches in the treatment of COPD patients.

Highlights

  • Chronic obstructive pulmonary disease (COPD) is currently listed as the 4th leading cause of death, with 328 million patients diagnosed worldwide [1]

  • These cytokines are produced by the airway epithelial cells and the macrophages activated within lung tissue (Figure 1)

  • Given the low solubility of tocotrienol in plasma, these results suggest that an independent mechanism apart from α-tocopherol transfer protein (α-TTP) transport may exist for the delivery of tocotrienol to the peripheral tissues

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Summary

Introduction

Chronic obstructive pulmonary disease (COPD) is currently listed as the 4th leading cause of death, with 328 million patients diagnosed worldwide [1]. Symptoms of COPD include dyspnea, productive cough, and mucus overproduction. Comorbid conditions such as cardiovascular disease and lung cancer reduce the survival rate of COPD patients [2]. Current treatment options for COPD include bronchodilators, such as long-acting ß2 -adrenergic receptor agonists (LABA) and long-acting muscarinic receptor antagonists (LAMA) These medications need to be taken daily for the prevention of disease exacerbations, a condition in which COPD increases in severity for a period of time [3]. Because of the persistent role of oxidative stress and inflammation in the development of the disease, we postulate that antioxidant and anti-inflammatory agents, notably the vitamin E molecules as evidenced by in vitro, in vivo, and human studies, have potential in COPD prevention. Previous studies have shown that, compared with individuals who never smoked, smokers and ex-smokers with symptoms of chronic bronchitis had a higher mortality risk (hazard ratio 2.89 and 1.69, respectively) [19]

Oxidative Stress in the Lung
Biological Mechanisms of COPD
Introduction to Tocopherols and Tocotrienols
Antioxidant and Anti-Inflammatory Effects of Tocotrienol
Antioxidant and Anti-Inflammatory Effects of Tocotrienol in COPD
10. Limitation
Findings
11. Conclusions and Future Directions
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