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.

Benefit Effect of Dendrobium officinale Ultrafine Powder on DSS-Induced Ulcerative Colitis Rats by Improving Colon Mucosal Barrier.

MATERIALS AND METHODS: After intragastric administration of DOFP for 3 weeks, the rat UC model was made by the administration of 4% oral DSS solution for one week, and the drug was given at the same time. During the experiment, the disease activity index (DAI) score of the rats was regularly computed. At the end of the experiment, the blood routine indexes of rats were obtained. The histopathological changes in the colon were monitored by hematoxylin-eosin (H&E) and PAS staining and observation of ultrastructural changes in the colon by transmission electron microscope. Occludin expression in the colon was monitored by Western blot, the expression of claudin-1 and ZO-1 in the colon was detected by immunofluorescence, and the expression of TNF-α, IL-6, and IL-1ß in the colon was detected by immunohistochemistry. RESULTS: The results firstly indicated that DOFP could significantly alleviate the signs and symptoms of the DSS-induced rats UC model, which manifested as improvement of body weight loss, increase of colon length, and improvement of the symptoms of diarrhea and hematochezia. Then, results from histopathology, blood routine examination, and transmission electron microscope analysis further implied that DOFP could dramatically reduce inflammatory cell infiltration and restore intestinal epithelial barrier integrity. In addition, the experiments of Western Blot analysis, immunofluorescence, and PAS staining also further confirmed that DOFP could markedly increase related protein expressions of the intestinal barrier and mucus barrier, as the expression of occludin, claudin-1, and ZO-1 in the colon significantly decreased. The experiments of immunohistochemistry confirmed that DOFP could markedly decrease protein expression levels of inflammatory cytokines TNF-α, IL-6, and IL-1ß. CONCLUSION: DOFP notably alleviated inflammatory lesions, repaired the colon mucosa damage by promoting the expression of tight junction proteins occludin, claudin-1, and ZO-1 and inhibiting the release of inflammatory factors TNF-α, IL-6, and IL-1ß, and finally achieved the purpose of treating UC.