Synthesis of 8-Fluoroneocryptolepine and Evaluation for Cytotoxic Activity against AGS Cancer Cells.

Neocryptolepine derivatives have attracted great interest because of their unique cytotoxic activity. 8-Fluoroneocryptolepine (8FNC) was synthesized, and its cytotoxicity was evaluated by MTT assay in AGS gastric cancer cells and gastric mucosa GES-1 cells. 8-Fluoroneocryptolepine showed greater selectivity and cytotoxicity to AGS cells than the cisplatin (CIS) and fluorouracil (5-Fu) commonly used in clinical treatment of gastric cancer. Most importantly, we significantly improved the cytotoxic effect of 8FNC against AGS cells by structural modification and reduced the cytotoxicity against GES-1 cells compared with neocryptolepine. We further evaluated the activity of 8FNC against AGS cells in vitro. Our results indicate that 8FNC arrests the AGS cell cycle in the G2/M phase, reduces the mitochondrial membrane potential of AGS cells, and drives the initiation of apoptotic body formation in 8FNC-induced apoptosis. Moreover, 8FNC exhibits strong inhibitory effects on AGS cell migration. Studies on the molecular mechanisms of the cytotoxic activities of 8FNC revealed that it may play a significant role in the inhibitory effect on AGS human gastric cancer cells through the PI3K/AKT signaling pathway. In conclusion, 8FNC may become a promising lead compound in the development of potential clinical drug candidates for the treatment of gastric cancer.

Oligopeptides from Jinhua ham prevent alcohol-induced liver damage by regulating intestinal homeostasis and oxidative stress in mice.

The current study aimed to evaluate the protective activity of peptides isolated from Jinhua ham (JHP) against alcoholic liver disease (ALD) and the mechanisms by which JHP prevents against ALD. The tangential flow filtration (TFF) combined with size exclusion chromatography (SEC) and reversed-phase high performance liquid chromatography (RP-HPLC) were used to isolate the JHP. Then the hepatoprotective activity of peptides was evaluated through experiments in mice. The primary structure of the peptide with the strongest liver protective activity was Lys-Arg-Gln-Lys-Tyr-Asp (KRQKYD) and the peptide was derived from the myosin of Jinhua ham, which were both identified by LC-MS/MS. Furthermore, the mechanism of KRQKYD prevention against ALD was attributed to the fact that KRQKYD increases the abundance of Akkermansia muciniphila in the gut and decreases the abundance of Proteobacteria (especially Escherichia_Shigella). The LPS-mediated liver inflammatory cascade was reduced by protecting the intestinal barrier, increasing the tight connection of intestinal epithelial cells and reducing the level of LPS in the portal venous circulation. KRQKYD could inhibit the production of ROS by upregulating the expression of the NRF2/HO-1 antioxidant defense system and by reducing oxidative stress injury in liver cells. This study can provide a theoretical foundation for the application of JHP in the protection of liver from ALD.