Kavalactones, a novel class of protein glycation and lipid peroxidation inhibitors (original) (raw)

Both advanced glycation endproducts (AGEs) and advanced lipoxidation endproducts (ALEs) 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 AGEs inhibitors. With IC50 values of 43.5 ± 1.2 M and 45.0 ± 1.3 M for kawain and methysticin, respectively, the compounds inhibited the in vitro protein glycation significantly better than aminoguanidine (IC50 = 231.0 ± 11.5 M; p = 0.01), an established reference compound. Kawain and methysticin also inhibited the formation of dicarbonyl compounds, which are intermediates in the process of AGEs formation. Similarly, kawain and aminoguanidine prevented the formation of thiobarbituric reactive substances (TBARs) in both low density lipoprotein (LDL) and linoleic acid oxidation. Moreover, kawain and aminoguanidine prevented AGEs formation by chelating Fe3+ and Cu2+ two-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 lifespan extending ability, kavalactones show a high potential as AGEs and ALEs inhibitors.

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Kavalactones, a novel class of protein glycation and lipid peroxidation inhibitors (original) (raw)

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