Baitouweng decoction alleviates dextran sulfate sodium-induced ulcerative colitis by regulating intestinal microbiota and the IL-6/STAT3 signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Baitouweng (BTW) decoction, a Chinese traditional medicine prescription, has been used to treat ulcerative colitis (UC) over hundreds of years. In this study, we investigated the anti-inflammatory effects of BTW and intestinal flora of dextran sulfate sodium (DSS)-induced UC mice, and we investigated the mechanism of BTW in the preliminary treatment of UC. AIM OF STUDY: The aim of this study was to elucidate the mechanism of BTW in treating UC through molecular biology and high-throughput sequencing. METHODS: DSS-induced UC mice were established and randomly divided into the following four groups: control group, DSS group, BTW group and sulfasalazine (SASP) group. Except for the control group, 3% DSS drinking water was given to each group for 7 days, and the other two groups were intragastrically administered with BTW and SASP. Mice were sacrificed after gavage for 10 days. Body weight loss, disease activity index (DAI), colon length, colon histopathology and the expression of inflammatory cytokines were measured. Intestinal content samples were collected, and intestinal flora differences were analyzed by 16 S rDNA sequencing. RESULTS: BTW effectively reduced the symptoms and histopathological score of UC mice, and it reduced the production of IL-6, IL-1ß and TNF-α. Activation of the IL-6/STAT3 pathway was also suppressed by BTW treatment. Moreover, 16 S rDNA sequencing showed that the intestinal flora of mice in the DSS group was disordered compared to the control group. After treatment with BTW, the diversity of intestinal flora was significantly improved. At the phylum level, the proportion of Firmicutes to Bacteroidetes was decreased, and the ratio of Proteobacteria was decreased. At the genus level, the relative abundance of Escherichia-Shigella was decreased, but that of Lactobacillus and Akkermansia were increased. CONCLUSION: BTW significantly improved the inflammatory symptoms of mice with acute colitis, and the latent mechanism of BTW may be related to various signaling pathways, including the modulation of intestinal microflora and inflammatory signaling pathways, such as IL-6/STAT3.

Clinical Trial of Vadadustat in Patients with Anemia Secondary to Stage 3 or 4 Chronic Kidney Disease.

BACKGROUND: Therapeutic options for the treatment of anemia secondary to chronic kidney disease (CKD) remain limited. Vadadustat (AKB-6548) is an oral hypoxia-inducible factor prolyl-hydroxylase domain (HIF-PHD) inhibitor that is being investigated for the treatment of anemia secondary to CKD. METHODS: A phase 2a, multicenter, randomized, double-blind, placebo-controlled, dose-ranging trial (NCT01381094) was undertaken in adults with anemia secondary to CKD stage 3 or 4. Eligible subjects were evenly randomized to 5 groups: 240, 370, 500, or 630 mg of once-daily oral vadadustat or placebo for 6 weeks. All subjects received low-dose supplemental oral iron (50 mg daily). The primary endpoint was the mean absolute change in hemoglobin (Hb) from baseline to the end of treatment. Secondary endpoints included iron indices, safety, and tolerability. RESULTS: Ninety-three subjects were randomized. Compared with placebo, vadadustat significantly increased Hb after 6 weeks in a dose-dependent manner (analysis of variance; p < 0.0001). Vadadustat increased the total iron-binding capacity and decreased concentrations of ferritin and hepcidin. The proportion of subjects with at least 1 treatment-emergent adverse event was similar between vadadustat- and placebo-treated groups. No significant changes in blood pressure, vascular endothelial growth factor, C-reactive protein, or total cholesterol were observed. Limitations of this study included its small sample size and short treatment duration. CONCLUSIONS: Vadadustat increased Hb levels and improved biomarkers of iron mobilization and utilization in patients with anemia secondary to stage 3 or 4 CKD. Global multicenter, randomized phase 3 trials are ongoing in non-dialysis-dependent and dialysis-dependent patients.

[Non-anthraquinone constituents from Rheum sublanceolatum C. Y. Cheng et Kao].

OBJECTIVE: Study on the non-anthraquinone constituents from rhizoma and radix of Rheum sublanceolatum. METHOD: The constituents were isolated through column chromatography and identified on the basis of their physiochemical and spectral data. RESULT: Six non-anthraquinone constituents were isolated and identified as n-octacosanic acid, sitosterol, daucosterol, 2-methyl-5-carboxymethyl-7-hydroxychromone, piceatannol and 6-hydroxymusizin-8-O-beta-D-glucopyranoside. CONCLUSION: All these compounds were firstly isolated from R. sublanceolatum.

[Protective effects of the pollen of Codonopsis pilosula (Franch.) Nannf. on liver lesions at the ultrastructural level].

The experimental hepatic lesion of C57 mice was induced by carbon tetrachloride (CCI4), and the feeds containing pollen of Codonopsis pilosula were given to the animals. It was found by electronic microscopy that these pollens evidently reduced the hepatic steatosis, improved liver necrosis, suppressed the formation of the collagen fibrils in Disse's spaces and around central veinules. It was shown that the pollens of Codonopsis pilosula could counteract efficiently the liver lesion of mice induced by CCI4.