Dendrobium officinalis Six Nostrum Promotes Intestinal Urate Underexcretion via Regulations of Urate Transporter Proteins in Hyperuricemic Rats

Abstract

Background: Dendrobium officinalis Six nostrum (DOS) can be prepared by adding Dendrobium officinalis into Simiao Wan in accordance with the Traditional Chinese Medicine (TCM) theory and other previous findings. Our previous study has shown that DOS treatment can lead to a marked decrease in Serum UA (SUA) levels. The purpose of this study was to explore the effects of DOS on intestinal UA excretion in hyperuricemia and its underlying mechanisms.

Methods: DOS was administered intragastrically to hyperuricemic rats induced by oral administration of HX and PO for 7 weeks. The SUA level, fecal UA and XOD activity were detected. The expressions of UA transporters (ABCG2, GLUT9, and PDZK1), CNT2, and tight junction proteins (ZO- 1 and claudin-1) in the intestine were assayed by IHC staining. The serum LPS and DAO levels were detected by ELISA kits. The intestinal histological changes were assessed using H&E staining.

Results: DOS treatment decreased the SUA level while markedly increasing the fecal UA level by 28.85%~35.72%. Moreover, DOS effectively up-regulated the expression of ABCG2 and PDZK1 and down-regulated the expression of GLUT9 in the intestine. DOS markedly decreased the serum LPS level by 21.4%~32.1% and DAO activity by 12.3%~19.7%, which in turn ameliorated the intestinal pathology. As a result, it could protect intestinal barrier function, as indicated by the increase of villus height (V), the reduction of the crypt depth (C), and the elevation of the V/C ratio. It also increased the expression of ZO-1 and claudin-1. In addition, DOS significantly down-regulated the expression of CNT2, which reduced purine nucleoside transportation from the intestine into the blood, and inhibited XOD activity, leading to a decrease in UA production.

Conclusion: DOS exerted anti-hyperuricemic effects via regulation of intestinal urate transporters and could protect intestinal barrier function by restoring the expressions of ZO-1 and claudin-1.

Keywords: Dendrobium officinalis six nostrum; hyperuricemia; intestinal barrier; intestinal excretion; uric acid; xanthine oxidase.