Potential of Orally Administered Quercetin, Hesperidin, and -Coumaric Acid in Suppressing Intra-/Extracellular Advanced Glycation End-Product-Induced Cytotoxicity in Proximal Tubular Epithelial Cells.

Advanced glycation end-products (AGEs) are associated with the dysfunction of proximal tubular epithelial (PTE) cells in lifestyle diseases. Urinary stones induce cytotoxicity in PTE cells, and various medicines have been developed to mitigate or prevent their generation/accumulation. The leaves of Blume/ Makino-used in Japanese folk medicine-contain quercetin, hesperidin, and -hydroxycinnamic (-coumaric) acid, which can suppress the cytotoxicity of intra-/extracellular AGEs. This review investigated the effects of quercetin, hesperidin, and -coumaric acid on PTE cells in terms of their metabolism following oral administration and the associated organs and bacteria. Current evidence indicates that, in PTE cells, non-metabolized quercetin and -coumaric acid may suppress intra-/extracellular AGE-induced cytotoxicity, whereas the metabolites of quercetin and hesperidin may inhibit the generation of AGEs. However, little is known of the effects of -coumaric acid metabolites. Quercetin, hesperidin, and -coumaric acid may collectively suppress the cytotoxicity of intra-/extracellular AGEs in PTE cells. This review on the current paradigm of / extract provides a useful baseline for the design of further preclinical and clinical investigations.