Dendrobium officinale Six nostrum promotes excretion of intestinal uric acid in hyperuricemia rat through inhibiting LPS/TLR4/NF-κB signaling pathway

Abstract

Background : To evaluate the effect of Dendrobium officinale Six nostrum (DOS) on promoting the intestinal excretion of uric acid (UA) in the rat model of hyperuricemia (HUA), and explored its possible mechanisms of action. Methods: In this study, HUA was induced in rat by administration of lipid emulsion (LE) for 6 weeks, meanwhile, the rat was orally administered with DOS for 6 weeks. Then the level of serum uric acid (SUA) and fecal uric acid (FUA) were measured by automatic biochemical analyzer. Lipopolysaccharide (LPS) in hepatic portal vein blood was detected by ELISA kit. The intestinal protein levels of ATP-binding cassette superfamily G member 2 (ABCG2) and glucose transporter 9 (GLUT9) were measured by Western blot assay. Toll-like receptor 4 (TLR4) and nuclear factor kappa-B (NF-κB) were determined by immunohistochemistry (IHC). Hematoxylin and eosin (H&E) staining was used to assess intestinal histological changes. Meanwhile, the main compositions of DOS were identified and determined by the High Performance Liquid Chromatography (HPLC). Results: According to HPLC analysis, acteoside and astilbin were identified as the main chemical components of DOS. Our results indicated that DOS significantly reduced SUA level and increased FUA level in the HUA rat induced by oral administration of LE for 6 weeks. IHC and Western blot showed that DOS could significantly increase protein level of ABCG2 and reduce protein level of GLUT9 in the intestine. It remarkably reduced the content of LPS in hepatic portal vein blood and decrease protein levels of TLR4 and NF-κB in the intestine. In addition, DOS could improve the histopathological changes of intestine through increasing the number of intestinal gland goblet cells, and recovering the complete and neatly-arranged structure of small intestinal epithelial cells. Conclusions: DOS has the effect of treating hyperuricemia, the molecular mechanism may be associated with up-regulating ABCG2 protein level, and down-regulating protein level of GLUT9 in the intestine to promote the intestinal excretion of UA, and then decreasing the SUA level. In addition, DOS can reduce the damage of inflammatory response to the intestine, improve the histopathological changes of intestine in HUA rat through inhibiting LPS/TLR4/NF-κB inflammatory pathway.