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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 #298531

Title: Synthesis and characterization of norbelladine, a precursor of Amaryllidaceae alkaloid, as an anti-inflammatory/anti-COX compound

item Park, Jae

Submitted to: Bioorganic and Medicinal Chemistry Letters
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/17/2014
Publication Date: 12/1/2014
Citation: Park, J.B. 2014. Synthesis and characterization of norbelladine, a precursor of Amaryllidaceae alkaloid, as a potent anti-inflammatory/anti-COX compound. Bioorganic and Medicinal Chemistry Letters. 1:24(23):5381-5384.

Interpretive Summary: Obesity is a serious health condition often associated with several chronic diseases such as diabetes, cardiovascular disease, hypertension, and chronic kidney diseases. Particularly, visceral obesity is strongly associated with increased reactive oxygen species (ROS), which are considered as major causes for developing several obesity-induced chronic diseases. In fact, the elevated levels of ROS can cause significant consequence to cellular signals and components such as lipids, proteins, and DNA, thereby shifting cell homeostasis. Especially related to COX-2 expression, several data suggest that the ROS-modified molecules may act as endogenous inducers of COX-2 responsible for increasing prostaglandin production during inflammatory and immune responses. Since ROS and COX have been considered to play significant roles in the initiation and/or progression of several chronic human diseases, there has been considerable research effort in order to find potent plant compounds with both anti-ROS and anti-COX activities. This study suggests that norbelladine found in various plants may be a potent compound able to provide significant anti-oxidant and anti-inflammatory effects via scavenging radicals and inhibiting COX enzymes, furthermore inhibiting NF-kB activation at relatively lower concentrations. The outcomes of this study will provide researchers in nutrition, molecular biology, and medicinal fields with important information about a new activity of norbelladine to quench radicals, inhibit COX enzymes and suppress NF-kB activation.

Technical Abstract: Rising ROS and systemic inflammation is often a serious concern in many disease conditions including obesity. Therefore, compounds with both anti-oxidant and anti-inflammatory activities are considered beneficial in preventing/treating several human chronic diseases. Norbelladine is an amine compound, a precursor for Amaryllidaceae alkaloids (e.g., belladine, crinamine, lycorine, and galanthamine) found in plants traditionally used for treating a variety of human diseases. However, little information is available about its potential health effects. Therefore, the amine was first synthesized, and its anti-oxidant and anti-inflammatory activities were investigated in this study. Also, the potential effects of the amine on NF-kB activation were investigated due to the critical involvement of ROS in NF-kB activation. Norbelladine was synthesized with more than 60% yield, analyzed by a HPLC method, and verified using NMR spectroscopic method. Then, its radical scavenging activity was investigated using DPPH- and superoxide radical assays. At the concentration of 10 microM, norbelladine was a potent compound able to quench DPPH-radical by 31 % (P < 0.05) and reduce superoxide radicals from xanthine oxidase by 33 % (P < 0.05). At the concentration of 0.25 microM, the amine also inhibited both COX-1 and COX-2 enzymes by 51 % and 25 % (P < 0.05), respectively. Furthermore, at the concentration of 10 microM, norbelladine inhibited NF-kB activation by 23 % (P < 0.05). In summary, the data suggests that norbelladine may be a potent compound to quench radicals, inhibit COX enzymes as well as suppress NF-kB activation at relatively lower concentrations.