IAVPGEVA, an octapeptide derived from soybean 11S globulin hydrolysis, also known as SGP8, has exhibited regulatory effects on lipid metabolism, inflammation, and fibrosis in vitro. Studies using MCD and HFD-induced nonalcoholic steatohepatitis (NASH) models in mice show that SGP8 attenuates hepatic injury and metabolic disorders. Mechanistic studies suggest that SGP8 inhibits the JNK-c-Jun pathway in L02 cells and liver tissue under metabolic stress and targets DPP4 with DPP4 inhibitory activity. In conclusion, the results suggest that SGP8 is an orally available DPP4-targeting peptide with therapeutic potential in NASH.
Globulins , Non-alcoholic Fatty Liver Disease , Soybean Proteins , Mice , Animals , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Dipeptidyl Peptidase 4/metabolism , Liver/metabolism , Globulins/metabolism , Mice, Inbred C57BL , Disease Models, Animal
The lacto-ghrestatin derived nonapeptide (LGP9), a bioactive peptide derived from lacto-ghrestatin in bovine milk with the sequence of LIVTQTMKG, was investigated to determine its effects on islet ß-cell dedifferentiation and associated mechanisms in type 2 diabetes mellitus (T2DM). On the animal level, type-2-diabetic (T2D) mice were generated by high-fat-diet (HFD) and streptozocin (STZ). LGP9 was given to T2D mice for four weeks at doses of 1 mg kg-1, 3 mg kg-1, and 9 mg kg-1. A variety of techniques (immunohistochemistry, western blot, QPCR, and ELISA) were employed to evaluate the impact of LGP9 on the diabetic injury. On the cellular level, the pancreatic cell lines, Rin-m5f cells and Min6 cells, were treated with high-glucose (HG) and high-glucose-high-lipid (HG/PA), respectively. The cell models were established to investigate the mechanism of LGP9 treatment on the islet ß-cell dedifferentiation. For the mechanism study, the PI3K/Akt/FOXO1 pathway was investigated by inhibiting FOXO1 with its inhibitor and siRNA. Results showed that LGP9 improved the ß-cell dedifferentiation, prevented the EMT process, and upregulated the PI3K/Akt/FOXO1 signaling in the pancreas of T2D mice. In addition, LGP9 promoted the structural and functional recovery of pancreatic islets and shielded the liver tissue in T2D mice. From the cellular level data, LGP9 prevented ß-cell dedifferentiation and EMT occurrence. To a certain extent, the inhibition of FOXO1 restored PI3K/Akt/FOXO1 pathway activation and prevented ß-cell dedifferentiation. In conclusion, these findings suggest that LGP9 ameliorated pancreatic ß-cell dedifferentiation via PI3k/Akt/FOXO1 signaling in vivo and in vitro.
Diabetes Mellitus, Type 2 , Animals , Mice , Diabetes Mellitus, Type 2/drug therapy , Phosphatidylinositol 3-Kinases/genetics , Proto-Oncogene Proteins c-akt/genetics , Milk , Cell Dedifferentiation , Peptides , Glucose
Pulmonary fibrosis (PF) is a progressive respiratory disease. Phycocyanin derived eicosapeptide (PP20) is a novel peptide derived from active protein C-phycocyanin in Cyanobacteria. The aim of our study was to explore the anti-fibrotic activity of the PP20 and its underlying mechanism. Characteristic features of pulmonary fibrosis in oleic acid (OA)-induced mice and epithelial-mesenchymal transition (EMT) in TGF-ß1-exposed A549 and HFL-1 cells with or without PP20 and the change of TGF-ß/Smad and MAPK signaling pathways were examined. Smad and MAPK agonists were used to explore the role of TGF-ß/Smad and MAPK signaling in TGF-ß1- induced collagen I expression in A549 cells and α-SMA expression in HFL-1 cells when treated with PP20. Our results showed that PP20 significantly alleviated the inflammatory response and tissue destruction, inhibited EMT, restored the imbalance of TIMP-1/MMP-9 and reduced collagen fiber deposition. Moreover, PP20 inhibited TGF-ß1-induced EMT and collagen I expression in A549 cells. PP20 could also inhibit the proliferation, and decrease TGF-ß1-induced the expression of collagen I and transformation of fibroblasts into myofibroblasts in HFL-1 cells. Additionally, animal experiments and cell experiments combined with pathway agonists have shown that PP20 can negatively regulate TGF-ß/Smad and MAPK pathways and show anti-fibrotic properties. PP20 may be a promising drug candidate for protection against pulmonary fibrosis.
Phycocyanin , Pulmonary Fibrosis , Animals , Humans , Mice , Transforming Growth Factor beta1
