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

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.

Ganluyin ameliorates DSS-induced ulcerative colitis by inhibiting the enteric-origin LPS/TLR4/NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD), that is associated with a significantly increased risk of colon cancer. As a classic traditional Chinese medicine, Ganluyin (GLY) has a long history as an anti-inflammatory medication, but its impacts on UC has not been established. AIM OF THE STUDY: This study aims to evaluate the protective effect and mechanism of GLY on a pathway involving enteric-origin lipopolysaccharide (LPS), toll-like receptor (TLR)4, and NF-κB in mice with dextran sulfate sodium (DSS)-induced UC. MATERIALS AND METHODS: After three weeks of intragastric administration of GLY, a UC model was induced in mice by administration of 4% DSS in drinking water for one week. The disease activity index (DAI) was measured, and histological staining was used to detect histopathological changes of colon. LPS content of the serum was measured by ELISA, and the expression of tight junction proteins and proteins related to TLR4/NF-κB pathway in colon were analyzed by immunohistochemistry or Western Blotting. The intestinal flora was analyzed by 16S rRNA sequencing. RESULTS: GLY improved the histological pathological changes of DSS-induced UC, as assessed by DAI, colonic mucosal damage, inflammatory cell infiltration, and goblet cell and mucus reduction. GLY also protected the intestinal mucosal barrier by increasing the expression of the tight junction proteins, occludin, claudin-1, and ZO-1 and by reducing the serum LPS content and decreasing the expression of TLR4, MyD88, NF-κB, IL-6, IL-1ß, and TNF-α proteins in colon. Analyses of the intestinal flora showed that GLY restored the homeostasis of the intestinal flora through increases in the abundance of Firmicutes and decreases in the abundance of Proteobacteria and Bacteroidetes, which is associated with the production of LPS. CONCLUSION: GLY might exert an anti-UC effect by improving the colonic mucosal barrier and inhibiting the enteric-origin LPS/TLR4/NF-κB inflammatory pathway, and restoring the homeostasis of the intestinal flora in UC mice. These discoveries lay a strong foundation for GLY as a UC treatment.

Dendrobium officinalis six nostrum ameliorates urate under-excretion and protects renal dysfunction in lipid emulsion-induced hyperuricemic rats.

AIM: Hyperuricemia (HUA) is a metabolic disease caused by the overproduction or underexcretion of uric acid (UA). Our previous study found that treatment with Dendrobium officinalis six nostrum (DOS) led to a significant reduction in serum UA (SUA) by inhibiting UA production and promoting UA excretion in a rat model of HUA induced by potassium oxonate (PO) and high-fat sorghum feed. In this study, we aimed to further investigate the effects of DOS on UA excretion by the kidney and intestine to explore whether DOS protects against histopathological changes, and to elucidate its possible mechanisms of action in a lipid emulsion (LE)-induced rat model of HUA. METHODS: The main chemical constituents of DOS were determined to be acteoside and astilbin by high-performance liquid chromatography (HPLC). Three different doses of DOS (3.3, 6.6, and 13.2 g/kg/day) were given to rats daily after induction of HUA by oral administration of LE for 8 weeks. The levels of creatinine (Cr) in serum and urine and UA in serum, urine, and feces were measured by an automatic biochemical analyzer. The expression of TLR4, NF-κB and urate transport-related transporters (URAT1, ABCG2, and PDZK1) in kidney was measured by Western blot (WB). Intestinal urate transporters (ABCG2 and GLUT9) expression was assayed by IHC and WB. Serum LPS and renal inflammatory factors (IL-6, IL-8 and TNF-α) levels were measured using enzyme-linked immunosorbent assay (ELISA) kits. Hematoxylin and eosin (H&E) staining was used to assess renal histological changes. RESULTS: DOS treatment significantly reduced the SUA and SCr levels by increasing urine volume, 24 h urine uric acid (UUA), fecal UA (FUA), urine creatinine (UCr), and fractional excretion of UA (FEUA) levels in hyperuricemic rats. Moreover, DOS effectively regulated URAT1, PDZK1, and ABCG2 protein levels in the kidney, as well as restored protein levels of GLUT9 and ABCG2 in the intestine. DOS markedly reduced serum LPS anddown-regulated renal TLR4 and NF-κB protein levels to suppress IL-6, IL-8, and TNF-α secretion. It also improved renal inflammation in hyperuricemic rats. In addition, DOS attenuated histopathological changes in the kidneys of LE-induced rats. HPLC analysis showed levels of acteoside and astilbin of 1.39 mg/g and 0.72 mg/g in DOS, respectively. CONCLUSION: DOS has anti-hyperuricemic and anti-inflammatory effects in a rat model of HUA. The molecular mechanism appears to involve the regulation of urate transport-related transporters including renal ABCG2, URAT1, and PDZK1, and intestinal GLUT9 and ABCG2, as well as the inhibition of the LPS/TLR4/NF-κB signaling to reduce IL-6, IL-8, and TNF-α secretion in hyperuricemic rats.