title: How does curcumin work with poor bioavailability? Clues from experimental and theoretical studies.
abstract: Curcumin is a natural product with multiple biological activities and numerous potential therapeutic applications. However, its poor systemic bioavailability fails to explain the potent pharmacological effects and hinders its clinical application. Using experimental and theoretical approaches, we compared curcumin and its degradation products for its biological activities against Alzheimer's disease (AD), including the superoxide anion radical (O2(.-))-scavenging activity, Aβ fibrils (fAβ) formation-inhibiting activity, and enzymatic inhibition activity. We showed that compared to the parent compound curcumin, the degradation products mixture possessed higher O2(.-)-scavenging activity and stronger inhibition against fAβ formation. The docking simulations revealed that the bioactive degradation products should make important contribution to the experimentally observed enzymatic inhibition activities of curcumin. Given that curcumin is readily degraded under physiological condition, our findings strongly suggested that the degradation products should make important contribution to the diverse biological activities of curcumin. Our novel findings not only provide novel insights into the complex pharmacology of curcumin due to its poor bioavailability, but also open new avenues for developing therapeutic applications of this natural product.
authors.affiliation: Shandong Provincial Research Center for Bioinformatic Engineering and Technique, School of Life Sciences, Shandong University of Technology, Zibo 255049, P. R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Shen
authors.affiliation: Shandong Provincial Research Center for Bioinformatic Engineering and Technique, School of Life Sciences, Shandong University of Technology, Zibo 255049, P. R. China.
authors.forename: Cui-Cui
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Shandong Provincial Research Center for Bioinformatic Engineering and Technique, School of Life Sciences, Shandong University of Technology, Zibo 255049, P. R. China.
authors.forename: Chun-Yan
authors.initials: CY
authors.lastname: An
authors.affiliation: Shandong Provincial Research Center for Bioinformatic Engineering and Technique, School of Life Sciences, Shandong University of Technology, Zibo 255049, P. R. China.
authors.forename: Hong-Fang
authors.initials: HF
authors.lastname: Ji
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D003474:Curcumin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D008954:Models, Biological; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D016166:Free Radical Scavengers; D013481:Superoxides; D003474:Curcumin