title: Kavalactones, a novel class of protein glycation and lipid peroxidation inhibitors.
abstract: Both advanced glycation endproducts and advanced lipoxidation endproducts are implicated in many age-related chronic diseases and in protein ageing. In this study, kawain, methysticin, and dihydromethysticin, all belonging to the group of kavalactones, were identified as advanced glycation endproduct inhibitors. With IC50 values of 43.5 ± 1.2 µM and 45.0 ± 1.3 µM for kawain and methysticin, respectively, the compounds inhibited the in vitro protein glycation significantly better than aminoguanidine (IC50 = 231.0 ± 11.5 µM; p = 0.01), an established reference compound. Kawain and methysticin also inhibited the formation of dicarbonyl compounds, which are intermediates in the process of advanced glycation endproduct formation. Similarly, kawain and aminoguanidine prevented the formation of thiobarbituric reactive substances in both low-density lipoprotein and linoleic acid oxidation. Moreover, kawain and aminoguanidine prevented advanced glycation endproduct formation by chelating Fe(3+) and Cu(2+) two to three times better than aminoguanidine. Furthermore, kawain increased the mean life span of Caenorhabditis elegans exposed to high glucose. With glycation inhibiting, lipid peroxidation inhibiting, metal chelating properties, and life span extending ability, kavalactones show a high potential as advanced glycation endproducts and advanced lipoxidation endproduct inhibitors.
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Atul
authors.initials: A
authors.lastname: Upadhyay
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Emmy
authors.initials: E
authors.lastname: Tuenter
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Rizwan
authors.initials: R
authors.lastname: Ahmad
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Adnan
authors.initials: A
authors.lastname: Amin
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Exarchou
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Sandra
authors.initials: S
authors.lastname: Apers
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Nina
authors.initials: N
authors.lastname: Hermans
authors.affiliation: Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Luc
authors.initials: L
authors.lastname: Pieters
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D002614:Chelating Agents / Q000494:pharmacology; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors*; D006031:Glycosylation / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology*; D019787:Linoleic Acid / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects*; D008077:Lipoproteins, LDL / Q000378:metabolism; D008136:Longevity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D011714:Pyrans / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: C107882:7,8-dihydromethysticin; D002614:Chelating Agents; D017127:Glycation End Products, Advanced; D006146:Guanidines; D007783:Lactones; D008077:Lipoproteins, LDL; D010936:Plant Extracts; D011714:Pyrans; D011753:Pyrones; D017392:Thiobarbituric Acid Reactive Substances; D019787:Linoleic Acid; D005947:Glucose; C076881:methysticin; C004479:pimagedine; C011889:kavain