Bergenin ameliorates diabetic nephropathy in C57BL/6 J mice by TLR4/MyD88/NF-κB signalling pathway regulation.

Bergenin (BG) is a polyphenolic substance which has therapeutic potential in the treatment of diabetic nephropathy (DN), a common complication of type II diabetes. However, the mechanisms underlying these effects remain unclear. We studied the protective effects and mechanisms of BG in DN mice, focusing on the TLR4/MyD88/NF-κB signalling pathway. C57BL/6 J mice were used as experiments (n=60), and 10 animals were randomly selected as normal control. The DN model was developed by administering an intraperitoneal injection of streptozotocin (40 mg/kg BW for three days) and a high-fat diet (n=50). BG (20, 40, and 80 mg/kg BW, once a day) was administered orally for four weeks. After BG treatment, the food and water intake of DN mice decreased, blood glucose levels decreased, and insulin resistance reduced. As a result, serum LDL-C, TC, and TG levels decreased; HDL-C levels increased; SOD, CAT, and GSH-Px levels decreased; and MDA levels increased. BG administration reduced AST, ALT, BUN, and CRE levels and inflammatory factors (including TNF-α, MCP-1, IL-1ß, and IL-6). Histopathology revealed a significant improvement in pathological damage to the liver, kidney, and spleen of mice treated with BG, and TLR4, MyD88, and NF-κB p65 were down-regulated at both mRNA and protein levels in the BG-treated group. Based on these results, BG therapeutic type II DN by hypoglycaemia, improving liver and kidney function, and anti-oxidative stress; reducing inflammation; and inhibiting the TLR4/MyD88/NF-κB signalling pathway. The results of this study suggest that BG can be used as an effective treatment for type II DN.

The protective effect of fish-derived cathelicidins on bacterial infections in zebrafish, Danio rerio.

Antibiotic-resistant bacteria are severe threats to aquaculture industry. Boosting and modulating host immune responses has been proved to be an effective strategy to combat with bacterial infections and there is an urgent need for novel immunomodulators. Cathelicidins is an important family of host defense peptides (HDPs) that possess direct antimicrobial activities and potent immunomodulatory properties. Several cathelicidins have been identified and characterized from diverse fish species. Considering the relatively conserved immune systems between different fish species, it is reasonable to speculate that cathelicidins from different fish species possess immunomodulating functions on the other fish species. In the present study, two fish-derived cathelicidins (CATH_BRALE and codCath1) were selected to investigate their protective effect on zebrafish with bacterial infections. They exhibited potent and broad-spectrum antimicrobial activities against the tested aquatic Gram-positive and Gram-negative pathogenic bacteria, with MIC values ranging 2.34-18.75 µg/ml for CATH_BRALE and 2.34-37.5 µg/ml for codCath1. And their antimicrobial effect is so rapid that they killed the bacteria within 60 min. Unlike conventional antibiotics, they kill bacteria by inducing bacterial membrane permeabilization and cell disruption. Besides direct antimicrobial activity, CATH_BRALE and codCath1 exhibited potent immunomodulatory functions by both inhibiting bacteria induced zebrafish pro-inflammatory cytokine gene (TNF-α, IL-1ß, and IL-6) expression and stimulating zebrafish chemokine gene IL-8 expression. In vivo challenge test proved that they could significantly decrease the bacterial numbers and enhance the survival rates of zebrafish. All the results above imply the great potential of CATH_BRALE and codCath1 as novel peptide immunomodulators in fish aquaculture industry.