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ARS Home » Northeast Area » Beltsville, Maryland (BHNRC) » Beltsville Human Nutrition Research Center » Diet, Genomics and Immunology Laboratory » Research » Publications at this Location » Publication #308269

Research Project: Health Promoting Roles of Food Bio-Active Phenolic Compounds on Obesity-Altered Metabolic Functions and Physiology

Location: Diet, Genomics and Immunology Laboratory

Title: Activity-guided isolation of a sirtuin2 inhibiting compound from coffee: structural and activity confirmation of Javamide-II (N-caffeoyltryptophan)and its cellular effects on histone H3 and alpha-tubulin

Author
item Park, Jae

Submitted to: PLoS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/12/2016
Publication Date: 3/17/2016
Citation: Park, J.B. 2016. Activity-guided isolation of a sirtuin2 inhibiting compound from coffee: structural and activity confirmation of Javamide-II (N-caffeoyltryptophan)and its cellular effects on histone H3 and alpha-tubulin. PLoS One. 11(3):e0150392.

Interpretive Summary: Alzheimer disease (AD) is a devastating neurodegenerative disease and its risk factors include obesity, oxidative stress, hypertension, and aging. Currently, an estimated 5.2 million Americans have AD, recognized as a great health concern. Unfortunately, the situation is likely getting worse because the baby boom generation may add more than 10 million to the total number of people with AD in the United States. Therefore, a great number of scientific studies have been performed to find potent compounds able to prevent/treat AD. As a result, some recent studies pointed out potential beneficial effects of sirtuin2 inhibitors on the progressive degeneration of neurons, although the underlying mechanisms are still being elucidated. In this paper, we demonstrated that Javamide-II (N-caffeoyltryptophan) found in coffee has strong sirtuin2 inhibition activity. The amide was isolated from coffee samples using a newly developed sirtuin2 inhibition activity-guided HPLC method, and its identification was also determined using HPLC and NMR spectroscopic methods. Javamide-II isolated from coffee is a potent compound able to inhibit sirtuin2 at relatively low concentrations (1 uM). This report suggests that N-caffeoyltryptophan in coffee is likely to inhibit sirtuin2, thereby possibly providing beneficial effects on human diseases. The outcomes of this study will provide researchers in nutrition, molecular biology, and medicinal fields with important information about the capacity of amides to inhibit sirtuin2, as well as its implication on human diseases such as neuronal degenerative diseases.

Technical Abstract: Coffee is a most consumed drink worldwide, with potential health effects on several chronic diseases including neuronal degenerative diseases. Interestingly, recent studies suggest that the inhibition of sirtuin2 may be beneficial in restoring cognition in Alzheimer’s disease. Therefore, in this paper, potential sirtuin2 inhibitors were screened using coffee samples. For this study, a HPLC method was developed and coffee samples were fractionated by the HPLC method. Then, the fractions were screened using a sirtuin2 inhibition assay. The screening led to the isolation of an active compound from the fraction with the highest inhibitory activity, and the chemical structure of the compound was determined as N-caffeoyltryptophan (Javamide-II) using HPLC and NMR spectroscopic techniques. At the concentration of 1 uM, Javamide-II inhibited sirtuin2 activity by 39% (P < 0.05), and the inhibition was quite dose-dependent between 0.1-20 'M. To confirm that Javamide-II is the compound able to inhibit sirtuin2, the amide was chemically synthesized and its capability of inhibiting sirtuin2 was evaluated. Both isolated and synthesized N-caffeoyltryptophan exhibited a very similar pattern of sirtuin2 inhibition (Ki = 9.8 uM), suggesting that Javamide-II may be a potent compound able to inhibit sirtuin2, noncompetitively. This study suggests that Javamide-II found in coffee is likely to inhibit sirtuin2, thereby providing potentially beneficial effects on human diseases including neuronal, degenerative, and other diseases.