Chronic obstructive pulmonary disease (COPD) is a respiratory condition characterized by irreversible airflow obstruction due to chronic inflammation. Cigarette smoke is the main etiologic factor associated with the development of COPD, for which there is no cure. Although bronchodilators and steroids are used in the treatment of COPD, only oxygen has been demonstrated to prolong survival of patients. Antioxidants and anti-inflammatory agents may be useful in the treatment of COPD. Many edible fruits are rich sources of polyphenolic antioxidants and anti-inflammatory compounds, and diets rich in fruits and vegetables are correlated with a reduced risk of COPD in men. Our preliminary data demonstrate that two plant-derived polyphenols, the novel depside jaboticabin and the anthocyanin delphinidin 3-glucoside, both from the Brazilian fruit Myrciaria cauliflora, have antioxidant and anti-inflammatory activities. Jaboticabin and delphinidin 3-glucoside both inhibit interleukin-8 induction in cells exposed to cigarette-smoke extract. We hypothesize that polyphenols, like jaboticabin and delphinidin 3-glucoside, will modulate the cigaretteinduced inflammatory, oxidative, and proteolyitic responses of the lung. We will test this by isolating a group of polyphenols from four edible fruits in the Ericaceae (blueberry) and Myrtaceae (myrtle), plant families rich in polyphenols. The purified polyphenols will be tested in vitro using antioxidant assays including 2,2- diphenyl-1-picrylhydrazyl and oxygen radical absorbance capacity, and anti-inflammatory assays for IL-8 and cyclooxygenase. The polyphenols will be prioritized for further study based on the activity in these assays as well as their structural uniqueness. Three of the polyphenols will undergo further mechanistic studies. The results will be used to select the most promising compound that will be tested in an in vivo animal model for COPD. This model has proved to be valuable in identifying causative mechanisms of COPD, and also provides an essential vehicle for drug discovery. An additional aim of this project is for the PI to participate in career developmental activities to make him more competitive for NIH R01 funding. We anticipate that the project will lead to the discovery of new and/or potent polyphenols that will serve as models for new therapeutic agents for the prevention and/or treatment of COPD.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Enhancement Award (SC1)
Project #
5SC1HL096016-03
Application #
7876954
Study Section
Special Emphasis Panel (ZGM1-MBRS-1 (CH))
Program Officer
Punturieri, Antonello
Project Start
2008-09-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2011-06-30
Support Year
3
Fiscal Year
2010
Total Cost
$285,250
Indirect Cost
Name
Herbert H. Lehman College
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
620128301
City
New York
State
NY
Country
United States
Zip Code
10468
Flores, Gema; Wu, Shi-Biao; Negrin, Adam et al. (2015) Chemical composition and antioxidant activity of seven cultivars of guava (Psidium guajava) fruits. Food Chem 170:327-35
Wu, Shi-Biao; Wu, Jing; Yin, Zhiwei et al. (2013) Bioactive and marker compounds from two edible dark-colored Myrciaria fruits and the synthesis of jaboticabin. J Agric Food Chem 61:4035-43
Flores, Gema; Dastmalchi, Keyvan; Wu, Shi-Biao et al. (2013) Phenolic-rich extract from the Costa Rican guava (Psidium friedrichsthalianum) pulp with antioxidant and anti-inflammatory activity. Potential for COPD therapy. Food Chem 141:889-95
Ma, Chunhui; Dastmalchi, Keyvan; Flores, Gema et al. (2013) Antioxidant and metabolite profiling of North American and neotropical blueberries using LC-TOF-MS and multivariate analyses. J Agric Food Chem 61:3548-59
Wu, Shi-Biao; Dastmalchi, Keyvan; Long, Chunlin et al. (2012) Metabolite profiling of jaboticaba (Myrciaria cauliflora) and other dark-colored fruit juices. J Agric Food Chem 60:7513-25
Flores, Gema; Dastmalchi, Keyvan; Dabo, Abdoulaye J et al. (2012) Antioxidants of therapeutic relevance in COPD from the neotropical blueberry Anthopterus wardii. Food Chem 131:119-125
Flores, Gema; Dastmalchi, Keyvan; Paulino, Sturlainny et al. (2012) Anthocyanins from Eugenia brasiliensis edible fruits as potential therapeutics for COPD treatment. Food Chem 134:1256-62
Dastmalchi, Keyvan; Flores, Gema; Wu, Shi-Biao et al. (2012) Edible Myrciaria vexator fruits: bioactive phenolics for potential COPD therapy. Bioorg Med Chem 20:4549-55
Quinlan, Rena F; Shumskaya, Maria; Bradbury, Louis M T et al. (2012) Synergistic interactions between carotene ring hydroxylases drive lutein formation in plant carotenoid biosynthesis. Plant Physiol 160:204-14
Bradbury, Louis M T; Shumskaya, Maria; Tzfadia, Oren et al. (2012) Lycopene cyclase paralog CruP protects against reactive oxygen species in oxygenic photosynthetic organisms. Proc Natl Acad Sci U S A 109:E1888-97

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