Abstract
IntroductionThe aim of the present study was to investigate the uric acid-lowering effect of several Kampo (Japanese) herbal medicines (Hachimijiogan, Hangekobokuto, Yokuininto, Keishibukuryogan, Rikunshito, Kakkonto and Goshakusan), in a drug-permeability mimicked model using human intestinal epithelial Caco-2 cells. MethodsCaco-2 cells pretreated with potassium oxonate (PO) were treated with each medicine. The protein levels of xanthine oxidase (XO), glucose transporter 9 (GLUT9), and organic anion transporter 3 (OAT3) were determined via immunoblot analysis and ELISA. Caco-2 cell protein expression was additionally analyzed via immunofluorescence staining. OAT3 transporter uptake assays were measured by HEK293 cells overexpressing system. The levels of renal injury biomarkers, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) were measured. ResultsThe results indicated that Hachimijiogan, Yokuininto and Goshakusan upregulated OAT3 protein levels (18%, 35% and 34%, respectively) and downregulated GLUT9 protein levels (69%, 49% and 63%, respectively), reversing the effects of PO. In addition, they remarkably inhibited XO activity (40%, 45% and 36%, respectively) as well as inflammatory renal injury biomarkers, NGAL (32%, 51% and 52%, respectively) and KIM-1 protein levels (55%, 41% and 41%, respectively). The nominated herbal medicines can modulate the expression of OATs involved in uric acid uptake, and may have anti-inflammatory actions via the suppression of acute kidney injury biomarkers. ConclusionKampo medicines, Hachimijiogan, Yokuininto and Goshakusan were demonstrated to have anti-hyperuricemic effects by suppression of XO activity and regulation of uric acid transport proteins. Furthermore, Hachimijiogan, Yokuininto and Goshakusan were found to reduce the activities of NGAL and KIM-1.
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