Polyphenols and Inflammation: Recent Advances and Perspectives
Summary
Prof. Schneider will explore the latest research on the anti-inflammatory properties of polyphenols. He will highlight their mechanisms of action, potential therapeutic applications, and emerging perspectives in managing inflammation-related diseases.
Curcumin is one of the most widely consumed dietary supplements. Curcumin is best known for its anti-inflammatory effects, with frequent use of curcumin dietary supplements by consumers seeking relief for arthritis, pain, and other inflammatory conditions. His interest has been to elucidate the chemical and molecular mechanisms of how curcumin exerts biological activity, using its anti-inflammatory activity as example. Curcumin is unstable in aqueous solution at physiological pH, resulting in rapid degradation. His Team has identified the degradation products and their mechanism of formation and characterized the overall degradation reaction as an autoxidation. Among the intermediates in the degradation reaction are unstable and reactive electrophiles featuring quinone methide and epoxide moieties. They hypothesized that these electrophiles may exert biological effects via protein adduction at redox-active cysteine residues of curcumin target proteins. They characterized binding of electrophilic curcumin degradation products to a cysteine residue of IkB kinase b (IKKb), the kinase that activates NF-kB, a transcription factor involved in inflammation and cancer. This supported the hypothesis that curcumin serves as a pro-drug and that its anti-inflammatory effects on NF-kB are mediated by its electrophilic degradation products. This was further confirmed upon analysis of covalent binding of the degradation products to a peptide containing the target cysteine within the redox-regulatory domain of IKKb. Our studies identified curcumin as a pro-drug requiring activation by metabolic oxidation in order to exert anti-inflammatory effects. Insufficient activation of curcumin in vivo may be contributing to a lack of showing clear therapeutic benefits in human clinical trials.
About Professor Claus Schneider
Dr. Claus Schneider obtained a PhD in food chemistry from the University of Wuerzburg, Germany in 1997. In 1998 Dr. Schneider moved to Vanderbilt University (Nashville, TN, U.S.A.) to work on aspects of stereocontrol in cyclooxygenase catalysis and the mechanism of formation of 4-hydroxy-nonenal during lipid peroxidation. He is now a Professor of Pharmacology at Vanderbilt University. Dr. Schneider’s research focuses on the identification and characterization of novel eicosanoid lipid mediators. In the polyphenol field, Dr. Schneider’s research has identified the chemical mechanisms of degradation of curcumin, resulting in hypotheses on how degradation products mediate biological effects of the parent compound. Dr. Schneider served as an Associate Editor for the journal Molecular Nutrition and Food Research from 2005 to 2016 and became a member of the executive editorial board thereafter. He has been on the editorial board of the Journal of Biological Chemistry since 2016 and became an associate editor of Free Radical Research in 2020.
