This study investigated the effects of oleanolic acid (OA) on hepatic lipid metabolism and gut–liver axis homeostasis in an obesity-related non-alcoholic fatty liver disease (NAFLD) nutritional animal model and explored possible molecular mechanisms behind its effects. The results revealed that OA ameliorated the development of metabolic disorders, insulin resistance, and hepatic steatosis in obese rats. Meanwhile, OA restored high-fat-diet (HFD)-induced intestinal barrier dysfunction and endotoxin-mediated induction of toll-like-receptor-4-related pathways, subsequently inhibiting endotoxemia and systemic inflammation and balancing the homeostasis of the gut–liver axis. OA also reshaped the composition of the gut microbiota of HFD-fed rats by reducing the Firmicutes/Bacteroidetes ratio and increasing the abundance of butyrate-producing bacteria. Our results support the applicability of OA as a treatment for obesity-related NAFLD through its anti-inflammatory, antioxidant, and prebiotic integration responses mediated by the gut–liver axis.

Oleanolic acid attenuates intestinal inflammation and intestinal tight junction barrier damage through the TLR4/NF-κB and MAPKs pathway.

Inflammation is the hallmark of Staphylococcus aureus (S. aureus)-induced mastitis. Given the interesting relationship between selenium levels and inflammation, this study aimed to demonstrate that selenium modulated the inflammation reaction by suppressing the nuclear factor kappa B (NF-κB) and mitogen activated protein kinase (MAPK) signalling pathways. RAW264.7 macrophages were treated with three different concentrations (1μmol/l, 1.5μmol/l, and 2μmol/l) of Na2SeO3 for 12h before infection with S. aureus for 6h, 8h, and 10h. The results showed that selenium significantly reduced the mRNA expression levels of tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). Furthermore, the release of TNF-α, IL-1β, and IL-6 was decreased significantly with selenium supplementation. In addition, selenium influenced the NF-κB signalling pathway by suppressing the activation of NF-κB p65 and degradation of inhibitory kappa-B (IκB). Selenium also suppressed extracellular regulated protein kinase (Erk), c-Jun N-terminal kinase (Jnk), and p38 phosphorylation through the MAPK signalling pathway. In conclusion, selenium played an anti-inflammation role in RAW264.7 macrophages infected with S. aureus by suppressing the activation of the NF-κB and MAPK signalling pathways.

Antibacterial peptides (APMs) are a new type of antibacterial substance. The relationship between their structure and function remains indistinct; in particular, there is a lack of a definitive and fixed template for designing new antimicrobial peptides. Previous studies have shown that porcine Protegrin-1 (PG-1) exhibits considerable antimicrobial activity and cytotoxicity. In this study, to reduce cytotoxicity and increase cell selectivity, we designed histidine-rich peptides based on the sequence template RR(XY)2XDPGX(YX)2RR-NH2, where X represents I, W, V, and F. The results showed that the peptides form more β-hairpin structures in a lipid-rich environment that mimics cell membranes. Among them, the antimicrobial peptide HV2 showed strong antibacterial activity against Gram-negative strains and almost no toxicity to normal cells. The results of our analysis of its antibacterial mechanism showed that peptide HV2 acts on the bacterial cell membrane to increase its permeability, resulting in cell membrane disruption and death. Furthermore, peptide HV2 inhibited bacterial movement in a concentration-dependent manner and had a more robust anti-inflammatory effect by inhibiting the production of TNF-α. In summary, peptide HV2 exhibits high bactericidal activity and cell selectivity, making it a promising candidate for future use as an antibiotic.