No abstract

Disturbance of circulating metabolites and disorders of the gut microbiota are involved in the progression of diabetic kidney disease (DKD). However, there is limited research on the relationship between serum metabolites and gut microbiota, and their involvement in DKD. In this study, using an experimental DKD rat model induced by combining streptozotocin injection and unilateral nephrectomy, we employed untargeted metabolomics and 16S rRNA gene sequencing to explore the relationship between the metabolic profile and the structure and function of gut microbiota. Striking alterations took place in 140 serum metabolites, as well as in the composition and function of rat gut microbiota. These changes were mainly associated with carbohydrate, lipid, and amino acid metabolism. In these pathways, isomaltose, D-mannose, galactonic acid, citramalic acid, and prostaglandin B2 were significantly upregulated. 3-(2-Hydroxyethyl)indole, 3-methylindole, and indoleacrylic acid were downregulated and were the critical metabolites in the DKD model. Furthermore, the levels of these three indoles were restored after treatment with the traditional Chinese herbal medicine Tangshen Formula. At the genera level, g_Eubacterium_nodatum_group, g_Lactobacillus, and g_Faecalibaculum were most involved in metabolic disorders in the progression of DKD. Notably, the circulating lipid metabolites had a strong relationship with DKD-related parameters and were especially negatively related to the mesangial matrix area. Serum lipid indices (TG and TC) and UACR were directly associated with certain microbial genera. In conclusion, the present research verified the anomalous circulating metabolites and gut microbiota in DKD progression. We also identified the potential metabolic and microbial targets for the treatment of DKD.

Cardiovascular disease has become the main cause of death among complications of diabetes. Myocardial fibrosis is a crucial pathological change of cardiovascular disease. Tangshen Formula (TSF) shows a good clinical effect in the treatment of diabetic kidney disease (DKD). However, whether TSF alleviates diabetes-associated myocardial fibrosis is still unknown. In the present research, we studied the effect and mechanism of TSF in the treatment of myocardial fibrosis in vivo and in vitro. We found that TSF treatment significantly downregulates myocardial fibrosis-related markers, including collagens I and III, and α-SMA. TSF also protects primary mouse cardiac fibroblast (CF) from transforming growth factor-β1- (TGF-β1-) induced damage. Moreover, TSF decreased the expression levels of TGF-β/Smad-related genes (α-SMA, collagens I and III, TGF-β1, and pSmad2/3), and increased Smad7 gene expression. Finally, TSF decreased the expressions of wnt1, active-β-catenin, FN, and MMP7 to regulate the Wnt/β-catenin pathway. Taken together, TSF seems to attenuate myocardial fibrosis in KKAy mice by inhibiting TGF-β/Smad2/3 and Wnt/β-catenin signaling pathways.

Ulvan is a water-soluble polysaccharide that is extracted from the algae Ulva pertusa (Chlorophyta). In this study, ulvan-calcium derivative (U-calcium) was prepared and calcium content was 5.2%. Ulvancalcium could effectively scavenge on 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazolie-6-sulfonic acid) (ABTS), hydroxyl, and superoxide radicals. The inhibition rate on superoxide radicals (•O 2-) was 83.14% at 0.2 mg/mL, and the scavenging activity of ABTS and hydroxyl radical (•OH) at 3.0 mg/mL was 58.45 and 43.65%, and that of DPPH radicals at 8.0 mg/mL was 57.37%. All results showed that the antioxidant activity of ulvan-calcium was stronger than that of ulvan. The ulvan-calcium maybe used as an antioxidant to remove ROS and resist excessive oxidative stress.

The high-sulfated derivative of Ulva pertusa polysaccharide (HU), with unclear structure, has better anti-hyperlipidmia activity than U pertusa polysaccharide ulvan (U). In this study, we explore the main structure of HU and its therapeutic effect against nonalcoholic fatty liver disease (NAFLD). The main structure of HU was elucidated using FT-IR and NMR (13C, 1H, COSY, HSQC, HMBC). The anti-NAFLD activity of HU was explored using the high-fat diet mouse model to detect indicators of blood lipid and liver function and observe the pathologic changes in epididymal fat and the liver. Results showed that HU had these main structural fragments: →4)-β-D-Glcp(1→4)-α-L-Rhap2,3S(1→; →4)-α-L-Rhap3S(1→4)-β-D-Xylp2,3S(1→; →4)-α-L-Rhap3S(1→4)-β-D-Xylp(1→; →4)-α-L-IdopA3S(1→4)-α-L-Rhap3S(1→; →4)-β-D-GlcpA(1→3)-α-L-Rhap(1→; →4)-α-L-IdopA3S(1→4)-β-D-Glcp3Me(1→; →4)-β-D-Xylp2,3S(1→4)-α-L-IdopA3S(1→; and →4)-β-D-Xylp(1→4)-α-L-IdopA3S(1→. Treatment results indicated that HU markedly decreased levels of TC, LDL-C, TG, and AST. Furthermore, lipid droplets in the liver were reduced, and the abnormal enlargement of epididymal fat cells was suppressed. Thus, HU appears to have a protective effect on the development of NAFLD.